Disparities in activity level and nutrition between patients with chronic hepatitis C and blood donors.
To compare physical activity levels and dietary choices of patients who have chronic hepatitis C (CHC) with those of blood donors (BDs). A prospective survey. A liver disease treatment center and a blood donor center from a nonprofit health system. A total of 149 subjects (93 with CHC and 56 BDs) participated. Subjects were 18 years or older and agreed to participate; those with CHC had no evidence of cirrhosis. All subjects provided basic clinical information and completed a nutrition survey, which contained questions about dietary choices and their frequency, and the Human Activity Profile, which measured maximum effort (Maximum Activity Score; MAS) and daily activity (Adjusted Activity Score; AAS). MAS and AAS scales and 13 indices on the nutrition survey. Independent samples t-tests, Pearson correlations, and multiple stepwise regression analyses were performed. No significant differences were found between BDs and patients with CHC in terms of age, gender, race, body mass index, hyperlipidemia, hypertension, or diabetes mellitus. Mean body mass index was 27.5, 17.8% had hyperlipidemia, and 9.6% had diabetes. BDs reported significantly more exercise per week (mean: patients with CHC = 193.6 minutes/week and BDs = 280.4 minutes/week; P = .039) and had a significantly greater MAS (mean: patients with CHC = 77.2 and BDs = 87.4, P = .0001) and AAS (mean: patients with CHC = 72.58 and BDs = 83.8, P = .0001). Stepwise multiple regression analysis proposed 2 models predicting AAS: the presence of CHC (R = .445; R(2) = .198; adjusted R(2) = .184); and the presence of CHC and presence of hypertension (R = .537; R(2) = .289; adjusted R(2) = .263). BDs consumed significantly more alcohol and starchy foods than did patients with CHC (P = .0001 and P = .031, respectively), which may be explained by the compliance of patients with CHC to their hepatologist's recommendations regarding the minimization of alcohol consumption. Persons with CHC participate in less activity and less vigorous physical activity than do BDs and consume less starch and alcohol. These data about activity level and dietary intake in patients with CHC are novel; few data on these topics have been published previously. Low level of activity adds a substantial risk to this overweight CHC population, many of whom have multiple components of metabolic syndrome.


Synthesis, Characterization, and Application of Oxo-Molybdenum(V)-Corrolato Complexes in Epoxidation Reactions.
Sharpless et al. have described, while performing the molybdenum-catalyzed epoxidation reaction of olefins using alkyl hydroperoxides, that the molybdenum-oxo moiety is an active catalytic species. Thus, continuous efforts have been made to synthesize molybdenum-oxo complexes of different ligand environments. While plenty of such works on molybdenum porphyrins are reported in the literature, related molybdenum corroles are very less reported. The synthesis and characterization of two new oxo-molybdenum(V)-corrolato complexes are described herein. Both the complexes have been fully characterized by several spectroscopic techniques in conjunction with single-crystal X-ray diffraction analysis. The efficacy of the oxo-molybdenum(V)-corrolato complexes for the catalytic epoxidation reaction of olefins with the help of hydroperoxides has also been explored. The catalytic application of oxo-molybdenum(V)-corrolato complexes in the epoxidation reaction has not been reported earlier. A mechanism has been proposed to explain the experimental findings.


Experiences, Functioning and Needs of Low-Income African American Mothers of Children With Asthma.
The purpose of this proposed study was to explore experiences, needs and functioning of low-income, African American caregivers of children with asthma in order to better understand symptom management. A qualitative, descriptive design was used. A purposive sampling technique was used to screen 32 caregivers of children with asthma, and 15 caregivers agreed to participate. Three main themes were identified: managing the symptoms; cultural beliefs and values; and culturally competent health care provider. For the caregivers culture disparity is not just about access to health services but instead the healthcare providers' understanding of the complexity of symptoms management.


Local dry vitrectomy combined with segmental scleral buckling and viscoelastic tamponade for rhegmatogenous retinal detachment with vitreous traction.
To demonstrate local dry vitrectomy combined with segmental scleral buckling and viscoelastic tamponade for the treatment of partial rhegmatogenous retinal detachment (RRD) with local vitreous traction in patients at high-risk for proliferative vitreoretinopathy (PVR). Eleven eyes of 11 patients were retrospectively studied, including 5 retinal dialysis and 6 retinal detachment (RD; 5 eyes with peripheral retinal hole and 1 eye with giant tear). All patients exhibited partial RD and local vitreous traction. Combined local dry vitrectomy without conventional infusion and segmental scleral buckling was performed. Viscoelastic fluid was injected into the vitreous cavity if needed. Demographic information, preoperative and post-operative complications, and outcomes were recorded. The mean age of the patients at presentation was 26.55±13.52y. All 11 patients obtained retinal reattachment after a single surgical intervention. Postoperative visual acuities were improved or remained stable in all patients. None of them developed complications, except for temporary mildly increased intraocular pressure in 3 cases. Combined local dry vitrectomy and segmental scleral buckling are effective for patients of RRD with local vitreous traction. The technique avoids many complications associated with regular surgery and was minimally invasive to both the external and internal eye.


Comparative cytological and histological assessment of 828 primary soft tissue and bone lesions, and proposal for a system for reporting soft tissue cytopathology.
The aim of the study was to evaluate the diagnostic utility of fine needle aspiration (FNA) cytology and core needle biopsies (CNBs) in a series of primary soft tissue and bone lesions and to test a possible system for reporting results of FNA cytology of soft tissue lesion. This retrospective study encompassed 828 primary soft tissue and bone lesions, analysed with FNA, CNB and/or surgical specimen in order to perform sensitivity/specificity as well as accuracy analyses. The series was then used to test a system for reporting soft tissue cytopathology with six categories and the risk of malignancy in each category was calculated. With a malignant diagnosis defined as positive test result, FNA and CNB analysis showed sensitivity of 87% and 94%, respectively, and specificity of 89% and 95%, respectively. FNA and CNB analyses identified the correct histopathological entity of the examined lesion in 55% and 66%, respectively. The risk of malignancy within the tested categories was non-diagnostic 42%, non-neoplastic 0%, atypia of unknown significance 46%, neoplasm benign 3%, neoplasm of unknown malignant potential 27%, suspicious for malignancy 72% and malignant 97%. FNA cytology is a suitable tool to determine the malignant potential of a sampled soft tissue/bone lesion but is inferior to CNB in defining the correct entity. A standardised reporting system might improve the clinical management of patients with soft tissue tumours examined primarily by FNA cytology.


Biotransformation of 2,4-dinitrotoluene by the beneficial association of engineered Pseudomonas putida with Arabidopsis thaliana.
2,4-dinitrotoluene (2,4-DNT) is a priority environmental xenobiotic pollutant which has toxic, mutagenic, and carcinogenic properties. Thus, its biodegradation by applying recent approaches such as taking advantage of plant-bacteria interactions is crucial. In this work, the genes from Burkholderia sp. R34, necessary for 2,4-DNT degradation, were integrated into wild-type Pseudomonas putida (P. putida) KT2440 genome, and this strain, named KT.DNT, was inoculated to soil in in vitro conditions. To estimate the disappearance of 2,4-DNT in contaminated soil, samples were taken from different time intervals, extracted and analyzed using high-performance liquid chromatography (HPLC). Biotransformation of 2,4-DNT increased gradually and the degradation in soil after 14-days of treatment with the bacterium was found to be the 97.1%, indicating that the engineered strain could be a remarkable candidate for in situ bioremediation of 2,4-DNT-contaminated sites. In addition, in vitro interaction of this bacterium with a model plant, Arabidopsis thaliana (A. thaliana), enhanced lateral root and root hair formation together with dry root weight. Moreover, the initial 2,4-DNT concentration was decreased to 68% within 2 h with the plant-associated KT.DNT in liquid culture. Hence, the usage of this bacterium with plants could also be a promising application for the 2,4-DNT biotransformation.


Purification and immobilization of recombinant variants of Brevundimonas diminuta glutaryl-7-aminocephalosporanic acid acylase expressed in Escherichia coli cells.
Modified chitin-binding domain (ChBD) from Bacillus circulans chitinase A1 with W42F mutation in chitin-binding site was genetically fused to different positions within alpha-subunit of glutaryl-7-aminocephalosporanic acid acylase (GLA) gene. Hybrid proteins were efficiently expressed in E. coli cells as soluble, enzymatically active and correctly processed holoenzymes. ChBD-GLA fusions were easily affinity purified on chitin column by changing the salt concentration of binding and elution buffer. The developed one-step affinity purification procedure is thus a promising approach for scaled-up isolation of GLA variants for preparation of industrial biocatalysts as well as for structure-functional studies.


Use of constructed wetlands to prevent overloading of wastewater treatment plants.
The fluctuation in the number of people in tourist areas affects the wastewater quality and quantity. Constructed wetlands (CWs) aim to simulate physical, chemical, and biological processes occurring in natural environments for wastewater treatment and are considered a sustainable system. The current study aimed at evaluating the effectiveness of in-vessel CWs for supporting the wastewaters treatment plants in periods of overloading. Such approach can be quickly implementable, economic, and the CWs can be fast regenerated in the framework of sustainable good practices. Three pilot scale CWs were prepared in as many containers layering 10 cm of gravel, 60 cm of sand and 10 cm of gravel, and placing pieces of giant reed rhizomes in the upper layers. The bottom of each CW had a tap, and CWs were irrigated with a real municipal sewage three times a week. Before each new irrigation, the tap was opened, and the effluent collected for determining gross parameters, elemental composition, and contaminants of emerging concern (CECs). CWs significantly reduced almost all gross parameters considered and half the CECs, except for a couple of metabolites of corresponding parental compounds. With regards to the potentially toxic elements, all reduced their concentration from the influents to the effluents. The results of this study were promising and highlighted good efficiency of constructed wetlands as pre-treatment of real municipal sewage to reduce the overloading of the wastewater treatment plant.


Tuberous sclerosis.
Tuberous sclerosis complex (TSC) is a genetic multisystem disorder characterized by widespread hamartomas in several organs, including the brain, heart, skin, eyes, kidney, lung, and liver. The affected genes are TSC1 and TSC2, encoding hamartin and tuberin respectively. The hamartin-tuberin complex inhibits the mammalian-target-of-Rapamycin (mTOR) pathway, which controls cell growth and proliferation. Variations in the distribution, number, size, and location of lesions cause the clinical syndrome to vary even between relatives. About 85% of children and adolescents with TSC have CNS complications, including epilepsy, cognitive impairment, challenging behavioral problems, and autism-like symptoms. Epilepsy generally begins during the first year of life, with focal seizures and spasms. The discovery of the mTOR pathway upregulation in TSC-associated lesions presents new possibilities for treatment strategy. Increasing understanding of the molecular abnormalities caused by TSC may enable improved management of the disease.


Mitochondrial modulation is involved in the hepatoprotection of Limonium sinense extract against liver damage in mice.
Limonium sinense (Girard) Ktze is a Chinese folk medicine used to treat fever, hemorrhage, hepatitis, and other disorders. The present research focused on the protective effects of L. sinense extracts (LSE) against liver damage. In this study the extract from the root of Limonium sinense was used. Aminotransferase activity detection, electron microscopy, mitochondrial function evaluation, RT-PCR and western blot were used to evaluate the hepatoprotection of LSE in LPS/d-GalN-intoxicated mice. Pretreatment with 100, 200 or 400mg/kg LSE significantly blocked the increase in both serum aspartate aminotransferase (sAST) and serum alanine aminotransferase (sALT) levels induced by treatment with LPS plus d-GalN (LPS/d-GalN). Ultrastructural observation by electron microscopy showed reduced hepatocyte nuclear condensation and less lipid deposition. The decrease in both the mitochondrial membrane potential (14.6%) and sensitivity to mitochondrial swelling induced by Ca(2+) (45.9%) observed in the liver of LPS/d-GalN-treated mice were prevented by pretreatment with LSE. In addition, different doses of LSE increased both the transcription and the translation of voltage-dependent anion channels (VDAC), which was down-regulated by LPS/d-GalN treatment. In summary, LSE protects livers against LPS/d-GalN-induced damage, possibly by mitochondrial mechanisms related to increased expression of VDAC.


The effects of apremilast on the QTc interval in healthy male volunteers: a formal, thorough QT study.
This study was conducted to evaluate the effect of apremilast and its major metabolites on the placebocorrected change-from-baseline QTc interval of an electrocardiogram (ECG). Healthy male subjects received each of 4 treatments in a randomized, crossover manner. In the 2 active treatment periods, apremilast 30 mg (therapeutic exposure) or 50 mg (supratherapeutic exposure) was administered twice daily for 9 doses. A placebo control was used to ensure doubleblind treatment of apremilast, and an openlabel, single dose of moxifloxacin 400 mg was administered as a positive control. ECGs were measured using 24-hour digital Holter monitoring. The two-sided 98% confidence intervals (CIs) for ΔΔQTcI of moxifloxacin completely exceeded 5 ms 2 - 4 hours postdose. For both apremilast dose studies, the least-squares mean ΔΔQTcI was < 1 ms at all time points, and the upper limit of two-sided 90% CIs was < 10 ms. There were no QT/QTc values > 480 ms or a change from baseline > 60 ms. Exploratory evaluation of pharmacokinetic/pharmacodynamic data showed no trend between the changes in QT/QTc interval and the concentration of apremilast or its major metabolites M12 and M14. Apremilast did not prolong the QT interval and appears to be safe and well tolerated up to doses of 50 mg twice daily.


Vasopressor peptides and depolarization stimulated Ca2+-entry into cultured vascular smooth muscle.
45Ca-uptake was measured in monolayers of cultured rat aortic smooth muscle cells. Sufficient extracellular 45Ca could be removed by a 90 second cold La3+ was to reveal stimulation of 45Ca-uptake by high K+-depolarization and the vasopressor peptides angiotensin II and vasopressin. The high K+-stimulated 45Ca-influx was blocked by a dihydropyridine-type Ca2+-antagonist while that stimulated by angiotensin II or vasopressin was not. The 45Ca-influx stimulated by high K+-depolarization was additive to that stimulated by angiotensin II. Vasopressin and angiotensin II stimulated 45Ca-fluxes were not additive. It is concluded that vasopressor peptides stimulate Ca2+-entry through receptor operated Ca2+-channels which are distinct from voltage gated Ca2+-channels.


Neural correlates of decision making with explicit information about probabilities and incentives in elderly healthy subjects.
Recent functional neuroimaging and lesion studies demonstrate the involvement of the orbitofrontal/ventromedial prefrontal cortex as a key structure in decision making processes. This region seems to be particularly crucial when contingencies between options and consequences are unknown but have to be learned by the use of feedback following previous decisions (decision making under ambiguity). However, little is known about the neural correlates of decision making under risk conditions in which information about probabilities and potential outcomes is given. In the present study, we used functional magnetic resonance imaging to measure blood-oxygenation-level-dependent (BOLD) responses in 12 subjects during a decision making task. This task provided explicit information about probabilities and associated potential incentives. The responses were compared to BOLD signals in a control condition without information about incentives. In contrast to previous decision making studies, we completely removed the outcome phase following a decision to exclude the potential influence of feedback previously received on current decisions. The results indicate that the integration of information about probabilities and incentives leads to activations within the dorsolateral prefrontal cortex, the posterior parietal lobe, the anterior cingulate and the right lingual gyrus. We assume that this pattern of activation is due to the involvement of executive functions, conflict detection mechanisms and arithmetic operations during the deliberation phase of decisional processes that are based on explicit information.


Association of automated data collection and data completeness with outcomes of intensive care. A new customised model for outcome prediction.
The Finnish Intensive Care Consortium coordinates a national intensive care benchmarking programme. Clinical information systems (CISs) that collect data automatically are widely used. The aim of this study was to explore whether the severity of illness-adjusted hospital mortality of Finnish intensive care unit (ICU) patients has changed in recent years and whether the changes reflect genuine improvements in the quality of care or are explained by changes in measuring severity of illness. We retrospectively analysed data collected prospectively to the database of the Consortium. During the years 2001-2008, there were 116,065 admissions to the participating ICUs. We excluded readmissions, cardiac surgery patients, patients under 18 years of age and those discharged from an ICU to another hospital's ICU. The study population comprised 85,547 patients. The Simplified Acute Physiology Score II (SAPS II) was used to measure severity of illness and to calculate standardised mortality ratios (SMRs, the number of observed deaths divided by the number of expected deaths). The overall hospital mortality rate was 18.4%. The SAPS II-based SMRs were 0.74 in 2001-2004 and 0.64 in 2005-2008. The severity of illness-adjusted odds of death were 24% lower in 2005-2008 than in 2001-2004. One fifth of this computational difference could be explained by differences in data completeness and the automation of data collection with a CIS. The use of a CIS and improving data completeness do decrease severity-adjusted mortality rates. However, this explains only one fifth of the improvement in measured outcomes of intensive care in Finland.


Detecting endogenous SUMO targets in mammalian cells and tissues.
SUMOylation is an essential modification that regulates hundreds of proteins in eukaryotic cells. Owing to its dynamic nature and low steady-state levels, endogenous SUMOylation is challenging to detect. Here, we present a method that allows efficient enrichment and identification of endogenous targets of SUMO1 and the nearly identical SUMO2 and 3 (SUMO 2/3) from vertebrate cells and complex organ tissue. Using monoclonal antibodies for which we mapped the epitope, we enriched SUMOylated proteins by immunoprecipitation and peptide elution. We used this approach in combination with MS to identify SUMOylated proteins, which resulted in the first direct comparison of the endogenous SUMO1- and SUMO2/3-modified proteome in mammalian cells, to our knowledge. This protocol provides an affordable and feasible tool to investigate endogenous SUMOylation in primary cells, tissues and organs, and it will facilitate understanding of SUMO's role in physiology and disease.


Individual Variability in Waist Circumference and Body Weight in Response to Exercise.
This study aimed to determine the magnitude of exercise-induced individual variability for waist circumference (WC) and body weight change after accounting for biological variability and measurement error. Determinants of response variability were also considered. Participants (53 ± 7.5 yr) were 181 adults (61% women) with abdominal obesity randomized to the following: control; low-amount, low-intensity exercise (LALI); high-amount, low-intensity exercise (HALI); or high-amount, high-intensity exercise (HAHI) for 24 wk. Unstructured physical activity was measured by accelerometer. The variability in response to exercise for WC and body weight (SDR) was isolated by subtracting the SD values for the change scores in the exercise group from that of the control group. The variability of response due to exercise (SDR) for change in WC was 3.1, -0.3, and 3.1 cm for LALI, HALI, and HAHI groups, respectively. Corresponding values for body weight were 3.8, 2.0, and 3.5 kg for LALI, HALI, and HAHI, respectively. The high-amount exercise groups yielded the highest proportion of individuals with a clinically meaningful response. No variables predicted the response to exercise (P > 0.05). Substantial variability in response to standardized exercise was observed for change in both WC and body weight after accounting for the variability not attributed to exercise. Potential determinants of the interindividual variability in response to exercise remain unclear.


Behavioral risk factors for obesity during health transition in Vanuatu, South Pacific.
The South Pacific archipelago of Vanuatu, like many developing countries, is currently experiencing a shift in disease burdens from infectious to chronic diseases with economic development. A rapid increase in obesity prevalence represents one component of this "health transition." To identify behaviors associated with measures of obesity in Vanuatu. Five hundred and thirty four adults from three islands varying in level of economic development were surveyed. Height, weight, waist, and hip circumferences; triceps, subscapular and suprailiac skinfolds; and percent body fat (%BF) by bioelectrical impedance were measured. Diet through 24-h dietary recall and physical activity patterns using a survey were assessed. We analyzed prevalence of obesity and central obesity based on multiple indicators (body mass index, %BF, waist circumference, and waist-to-height ratio), and analyzed differences among islands and associations with behavioral patterns. Obesity prevalence was lowest among rural and highest among suburban participants. Prevalence of central obesity was particularly high among women (up to 73.9%), even in rural areas (ranging from 14.7 to 41.2% depending on the measure used). Heavier reliance on animal protein and incorporation of Western foods in the diet-specifically, tinned fish and instant noodles-was significantly associated with increased obesity risk. Even in rural areas where diets and lifestyles remain largely traditional, modest incorporation of Western foods in the diet can contribute to increased risk of obesity. Early prevention efforts are thus particularly important during health transition. Where public health resources are limited, education about dietary change could be the best target for prevention.


Occupational injuries: is job security a factor?
Although a large number of contributing factors of occupational injury causation are explored meticulously to explain the phenomenon of higher occupational injury occurrence in some subjects, it has remained a matter of controversy. In this study, an effort is made to explore whether job security has any contribution in explaining higher susceptibility of some workers. This was a retrospective occupational injury record study conducted in an industry of eastern India. Along with the study of injury records of 5 years, an interview was also conducted involving 726 workers (including permanent and temporary workers both) of the factory. Comparison was made between permanent and temporary workers by using the Mann-Whitney U-test and the chi-square test. A theoretical model of Poisson's distribution was used to compare between expected and real occurrence. Although two worker groups were very similar in relation to age, level of education, habits, and nature of work, accident frequency and severity rates were found to be significantly higher in temporary workers. This study concluded that the higher accident risk of the temporary workers might have been due to the less effective experience as well as due to lack of job security inherent in such workers.


Extracorporeal membrane oxygenation with lepirudin anticoagulation for Wegener's granulomatosis with heparin-induced thrombocytopenia.
Venovenous extracorporeal membrane oxygenation with lepirudin anticoagulation was successfully used for a complicated case of Wegener's granulomatosis and heparin-induced thrombocytopenia. Interestingly, a linear correlation was found between activated partial thromboplastin time and activated clotting time during lepirudin anticoagulation.


Hypervalent Iodine-Mediated Fluorination of Styrene Derivatives: Stoichiometric and Catalytic Transformation to 2,2-Difluoroethylarenes.
Fluorination of styrene derivatives with a reagent system composed of μ-oxo-bis[trifluoroacetato(phenyl)iodine] and a pyridine·HF complex gave the corresponding (2,2-difluoroethyl)arenes in good yields. Similarly, the reagent of PhI(OCOCF3)2 and the pyridine·HF complex acted as a fluorinating agent for styrene derivatives. The fluorination of styrene derivatives with the pyridine·HF complex underwent under catalytic conditions using 4-iodotoluene as a catalyst and m-CPBA as a terminal oxidant.


Does history-taking affect learning of attitudes?
How can medical students adopt a patient-oriented approach? During the past 7 years approximately 60 preclinical and clinical students joined dynamically oriented group sessions on medical history-taking. An open-ended question technique was used. The student's expectations of the patient were monitored by the repertory grid technique using a self-developed dyad grid form which allowed the estimation of reciprocal expectations as seen by the student. A main component analysis of the ratings obtained was performed. The development in one group was taken as representative of the general development in the different groups. Two main components (MC I, II) were found to account for approximately 40 and 25% of the total variance (distance/empathy and dominance/dependence). The student's main concern is centered on the problem of dependence, MC II. He expects the patient to cling to him. Similarly he feels dependent on the psychosomatic lecturer. He feels as though he is the lecturer's patient. During group work the patient is seen to be less clinging. The student learns that he is not his lecturer's patient but his junior partner. He changes his professional ego-ideal as a future doctor. This is modelled according to his own relationship with the lecturer. It is not modelled according to the usual doctor-patient relationship as perceived by the student. The main characteristic of the change is a lessening of dependency needs as felt in the relationship to the patient. The findings are interpreted as an attitudinal change in favour of a more patient-oriented attitude. The change was affected through confrontation with the patient's needs. Conclusions were drawn: The student has to be trained how to cope with dependency needs. Special learning settings have to be provided which are staffed with patient-oriented physicians.


Molecular and developmental effects of exposure to pyrene in the early life-stages of Cyprinodon variegatus.
Polycyclic aromatic hydrocarbons (PAHs) have been connected to developmental toxicity in the early life-stages of many species by their ability to bind to the aryl hydrocarbon receptor (AHR), which dimerizes with ARNT (AHR nuclear translocator) to induce transcription of genes such as CYP1A1. ARNT also dimerizes with HIF (hypoxia-inducible factor alpha) to induce transcription of genes such as VEGF (vascular endothelial growth factor), suggesting that PAHs may interfere with transcription of VEGF by competing for ARNT. Herein, we address the molecular and developmental effects of exposures to the weak AHR agonist pyrene on the early life-stages of the sheepshead minnow Cyprinodon variegatus. Embryos were exposed under flow-through conditions to 0, 20, 60, or 150 ppb pyrene up to 432 hours post-fertilization (hpf). RNA was extracted at 5 time points (12, 24, 48, 96, and 432 hpf) and changes in CYP1A1 and VEGF expression were assessed by real-time RT-PCR. Since few genes have been documented for the sheepshead minnow, we first cloned and sequenced CYP1A1, VEGF and internal standard 18S rRNA. Pyrene significantly induced the AHR-regulated gene, CYP1A1, in a time- and dose-dependent manner, while pyrene failed to alter the HIF-regulated gene, VEGF. However, VEGF was found to change during various stages of normal development in this study. Although a normal hatch time (5 dpf) was observed for all treatments, pyrene-treated embryos showed dose-dependent abnormalities such as severe dorsal body curvature, mild pericardial and yolk-sac edema, and increased mortality. Taken together, these data indicate that embryonic exposure of sheepshead minnows to pyrene disrupts normal development and alters expression of an AHR/ARNT-regulated gene. In addition, embryonic exposure to pyrene failed to provide evidence of possible AHR-HIF pathway cross-talk since developmental expression of VEGF was unaltered.


Interferon in nasal secretions from infants with viral respiratory tract infections.
Interferon levels in nasal secretions of infants under one year of age, and hospitalized with lower repiratory tract disease, were measured during two respiratory infection seasons. In the first year serial secretions from 50 infants with respiratory syncytial virus infection were examined. Undetectable or low levels of interferon were found in all samples, and mean levels did not fluctuate significantly in relation to disease and recovery. This was in contrast to anti-RSV IgA, which appeared and increased in concentration as virus shedding decreased and stopped. In the second year secretions were obtained from nine infants with influenza A virus infection as well as from 13 with RSV. All those with influenza developed measurable interferon in secretions (geometric mean titer 138 units/ml), which was acid and heat stable, and trypsin sensitive (type I interferon). RSV infection again stimulated very low levels (geometric mean 5 units/ml). The lack of correlation of interferon concentration with cessation of RSV shedding suggests either that it is not involved in recovery or that low levels are adequate. On the other hand, it appears that the young infant is fully capable of a brisk local interferon response, at least to infection by influenza A.


Oriented-aptamer encoded magnetic nanosensor with laser-induced fluorescence for ultrasensitive test of okadaic acid.
Okadaic acid (OA) biotoxin acts a well-established inhibitor of protein phosphatase even a tumor promoter of human being, arouse great attention in safety monitoring. However, the powerful and convenient nanosensing technologies for addressing the demands such as rapidity, high sensitivity, and stability in the in-field test of OA shellfish toxin is still scarce. Herein, a high-performance magnetic biometric nanosensor (MBNS) integrating oriented aptamers and ultrasensitive laser-induced fluorescence (LIF) was firstly proposed for the in-field detection of trace OA in seafoods. High-density aptamers hybridized with FAM-labeled cDNA were tethered to the surface of AuNPs on magnetic MIL-101@Fe3O4, and then finely regulated by mercaptohexyl alcohol (MCH) to be orderly assembled, as was successfully utilized to engineer an active biological nanosensor for highly specific recognition of OA. Aptamers anchored on magnetic Fe3O4@MOF@AuNPs activate a biometric microreactor of OA, in which the superior LIF properties, conformation regulation of aptamer, and the specific recognition using aptamer genes were adopted. The magnetic nanosensor with an excellent specificity and super sensitivity for OA analysis was achieved within 20 min. Moreover, the content of captured OA could facilely be recorded by measuring the fluorescence intensity, and the limit of detection (LOD) and limit of quantitation of OA (LOQ) reached 0.015 and 0.050 ng/mL respectively, which was far better than most aptamer-based biometric sensing methods. The feasibility for accurate test of trace OA toxin in the fortified shellfish samples was validated with the recovery yields of 88.2-107.5% and RSD of 0.5-7.6%, respectively. The result demonstrated that the oriented-aptamer encoded MNS had significant practical values in rapid and ultrasensitive detection of OA biotoxin and the related safety applications.


Safety evaluation of an IPP tripeptide-containing milk protein hydrolysate.
Tensguard is a milk protein hydrolysate containing the lactotripeptide IPP. It is derived from cow's milk, which is present in the human diet and has a safe history of consumption. The final Tensguard product, a supplement or a functional food ingredient, is intended for use by people who want to follow a healthy diet and lifestyle in order to manage their blood pressure. The safety-in-use of commercial lactotripeptide-containing products has been confirmed in several in vitro and in vivo toxicity studies and in studies with humans. To support the safety, Tensguard was examined in three in vitro genotoxicity tests (bacterial reverse mutation test, mammalian cell gene mutation test and mammalian chromosomal aberration test) and in a 90-day repeated-dose oral toxicity study in rats. The genotoxicity tests confirm that Tensguard is not mutagenic or clastogenic. The NOAEL from the 90-day study was at the highest dose tested, i.e. 4% in the diet. The NOAEL is equivalent to an overall mean intake of 2 g Tensguard/kg body weight/day and corresponds to 40 mg IPP/kg body weight/day. This is 141-fold higher than the maximal anticipated intake. In conclusion, Tensguard is safe under the conditions of intended use.


Nocardia infection in the acquired immunodeficiency syndrome.
A case of Nocardia asteroides pneumonia in a patient with the acquired immunodeficiency syndrome who was intolerant of sulfadiazine is described. On cefuroxime, the patient had a complete resolution of his Nocardia pneumonia. Disk-diffusion and broth microdilution antibiotic susceptibility testing (MIC less than or equal to 2 micrograms/ml) strongly supported the use of cefuroxime as treatment in this patient. Susceptibility testing with newer cephalosporins should be considered for all significant Nocardia isolates.


The biological basis of a comprehensive grading system for the adverse effects of cancer treatment.
As described in the previous article in this issue by Trotti et al, there have been major changes in the philosophy and scope of the new National Cancer Institute comprehensive grading system for treatment-related toxicities, Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0). The most prominent changes are the merging of early and late effects criteria into a single uniform document and the development of criteria that cover all treatment modalities. In this article, we briefly outline the biological support for the new grading system in the context of our current knowledge base. The clinical consequences of radiotherapy in normal tissue have been classically grouped temporally, into early and late effects, using a somewhat arbitrary dividing line, 90 days after commencement of radiotherapy. This definition was developed in an era of standard fractionation used alone or in simple sequential programs involving other modalities. However, most patients are now managed with multiple highly integrated modalities, often augmenting tissue injury and limiting our ability to ascribe any given effect to a particular modality. The use of complex concurrent or hybrid (concurrent/sequential) schedules also undermines the usefulness of a simplistic temporally defined early-late construct. Moreover, there is growing recognition that chemotherapy and surgery produce inherent long-term biologic and clinical effects as well. Our basic understanding of the roles that surgery, chemotherapy, and radiation play in normal tissue response has expanded over the last decade because of vastly improved molecular techniques. The original biologic paradigm viewing acute and late tissue injury as a continuum of response and repair has been strengthened by these additional laboratory investigations. The expression of toxicity over time has been shown to be caused by a variety of cellular, tissue, environmental, and host factors. We continue to elucidate the roles of DNA damage, cytokines, chemokines, and associated inflammation, which lead in some cases to perpetuation of the wound-healing response, progressive tissue fibrosis, and vascular compromise. The continuum model of tissue injury supports the recent changes in the common toxicity grading system. It also provides insights into potential targets and strategies for modulating response, which may in turn lead to effective interventions for altering the therapeutic ratio.


Mechanisms whereby lytic granules from cytotoxic T lymphocytes damage guinea pig ventricular myocytes.
During immunological rejection of the transplanted heart, cytotoxic T lymphocytes (CTL) infiltrate the myocardium and by damaging the myocytes contribute to loss of function. To address one important aspect of heart transplant rejection, we investigated in guinea pig ventricular myocytes how CTL-derived lytic granules containing the pore-forming protein perforin reduce the membrane potential (VM) and cause cell damage. The reduction in VM was biphasic; within 8.4 +/- 1.9 min VM was reduced from a control value of -78.4 +/- 1.9 mV to -69.9 +/- 3.5 mV. Subsequently, within 6.7 +/- 2.1 min VM declined to -3.4 +/- 1.2 mV, associated with a progressive contracture. Under whole cell voltage clamp, in myocytes held at their resting potential (VM = -76.2 +/- 0.9 mV), granules induced discrete inward current steps (resembling 'single channel' activity), with a mean amplitude of -86.8 +/- 1.4 pA and open times lasting from seconds up to several minutes. The mean conductance and reversal potential calculated from the linear regression analysis of the I-V relations were 1390 pS and -6.8 mV, respectively. The probable non-selectivity of these 'channels' and the resultant loss of membrane K+ selectivity can account for the reduction in VM. At the same time, opening of these pores leads to Ca2+ overload, resulting in contracture and cell damage.


Contralateral suppression of otoacoustic emissions: input-output functions in neonates.
The literature suggests that contralateral acoustic stimulation (CAS) alters the amplitude of the distortion product otoacoustic emissions (DPOAEs), but it is still unknown whether the DPOAE Input/Output (I/O) functions are also affected. To elucidate this aspect of the DPOAEs, the present study assessed the effects of CAS on DPOAE I/O functions at the frequencies of 2 kHz and 4 kHz, in a sample of term neonatal subjects. Sixty randomly selected neonates were included in the study. The DPOAE I/O functions were obtained at 2 kHz and 4 kHz, in the presence of a 60 dB SPL broad band-contralateral white noise, using the TDH39 headphones contralaterally. DPOAEs were recorded up to a stimulus level of L2 = 35 dB peSPL. Significant DPOAE amplitude suppression effects were observed at various L2 stimulus levels for both tested frequencies at 2 and 4 kHz. In contrast, the corresponding DPOAE slopes showed various alterations that were not statistically significant. The data from the present study show that contralateral acoustic stimulation significantly affects only the amplitude of the DPOAE I/O functions; the slope is affected, but not significantly. This observation can shed light on the nature of CAS, suggesting that the latter is primarily a linear phenomenon without the cochlear compression and non-linear components seen in the healthy cochlea. From the available data it is not possible to infer whether the sample size has influenced the obtained results and the study should be repeated with a larger sample size and assessing more frequencies.


Trends of inorganic sulfur and nitrogen species at an urban site in western Canada (2004-2018).
A 15-year (2004-2018) record of measurement data of gaseous and particulate sulfur and nitrogen pollutants in air collected at an urban site in Burnaby in western Canada was analyzed for generating their decadal trends using three different methods, including linear regression, Mann-Kendall test and Theil-Sen trend estimator (MK-TS), and ensemble empirical mode decomposition (EEMD). Annual mean concentration of SO2 and SO42- decreased by about 59% and 42%, respectively, during the 15-year period. The slower decreases of SO42- than SO2 were mainly caused by the increased O3 concentration and temperature in spring and summer, which promoted conversion of SO2 to SO42- through gas-phase reaction, and by the increased aerosol pH value and availability of H2O2 in winter, which enhanced aqueous-phase SO42- formation. Accordingly, the sulfur oxidation ratio (SOR) increased by 23% or more in spring, summer, and winter during the 15-year period. Annual mean concentrations of NO2 and NO3- declined by 36% and 38%, respectively, during this period. On seasonal basis, NO3- decreased faster than NO2 in autumn and slower in winter. The non-linear responses of NO3- to NO2 concentration decreases were more evident in winter than the other seasons, partly due to the increased particulate NO3- fraction caused by decreased temperature, increased aerosol pH value, and enhanced NO3- formation caused by increased O3 concentrations. Annual mean concentration of NH3 showed small increases due to stable NH3 emission and reduced conversion of NH3 to NH4+. NH4+ concentration decreased by 51% during the 15-year period. These results suggest that reduced oxidants levels are likely responsible for weakened formation of secondary inorganic aerosols, besides emission reductions for SO2 and NO2.


Oral contraceptives and mood in women with and without premenstrual dysphoria: a theoretical model.
Despite numerous studies on the topic, there is no consensus to date on the effects of oral contraceptives on mood or the mechanism(s) by which they exert these effects. This review article presents a theoretical model to explain the way in which oral contraceptives may affect mood. Specifically, it is argued that progestins exert differential effects on endogenous levels of neurosteroids, thereby altering mood. After providing an overview of the effects of estrogen, progesterone, and progesterone's metabolites on cortical excitability and the role of neurosteroids in depression and premenstrual dysphoria, this article reviews the research that has been conducted on the relationship between oral contraceptives and neurosteroids. Finally, suggestions for future research are made with the dual aim of improving existing studies on the relationship between oral contraceptives and mood and further investigating the possibility that fluctuations in neurosteroid levels are responsible for the effects of oral contraceptives on mood.


Face templates for the Chicago Face Database.
Researchers often need to manipulate faces, such as developing a continuum between two faces or averaging a set of faces. In order to do so, researchers use morphing software, but they first need to fit a template to the idiosyncratic landmarks in each face. In this paper, we present a set of landmark templates for the Chicago Face Database (CFD; Ma, D. S., Correll, J., & Wittenbrink, B. (2015). The Chicago Face Database: A free stimulus set of faces and norming data. Behavior Research Methods, 47(4), 1122-1135). The CFD is a free online face database containing images of faces of people from various races and genders. We provide templates for each of 597 neutral (non-expressive) faces in version two of the CFD. Our templates are unique because the facial landmarks were hand placed by researchers. Hand placing facial landmarks allows for more accurate placement of landmarks than a computer-generated template. Historically, hand-placed templates were created by individual labs and not shared. In this paper, we describe how our templates were created, and some possible uses for the templates. We hope that our templates ease the burden for other researchers to manipulate faces.


Computational prediction of protein interfaces: A review of data driven methods.
Reliably pinpointing which specific amino acid residues form the interface(s) between a protein and its binding partner(s) is critical for understanding the structural and physicochemical determinants of protein recognition and binding affinity, and has wide applications in modeling and validating protein interactions predicted by high-throughput methods, in engineering proteins, and in prioritizing drug targets. Here, we review the basic concepts, principles and recent advances in computational approaches to the analysis and prediction of protein-protein interfaces. We point out caveats for objectively evaluating interface predictors, and discuss various applications of data-driven interface predictors for improving energy model-driven protein-protein docking. Finally, we stress the importance of exploiting binding partner information in reliably predicting interfaces and highlight recent advances in this emerging direction.


Comparative genetic diversity and structure of Rhus gall aphid Schlechtendalia chinensis and its host plant Rhus chinensis.
Investigating the population genetic structure of parasites and their host plants can provide valuable insights into their coevolutionary processes. In this study, we assessed and compared the population genetic diversity and structure of 12 Rhus gall aphid (Schlechtendalia chinensis) populations and their respective host plant (Rhus chinensis) using amplified fragment length polymorphism (AFLP) markers. Analysis of molecular variance (AMOVA) revealed that both the aphid and its host plant exhibited higher genetic variance within populations than among them, indicating that their coevolutionary history may have produced analogous patterns of population genetic structure. Additionally, we considered alternative factors that could contribute to this outcome, such as intraspecific gene flow, hybridization, or environmental influences. Our analysis did not reveal a significant correlation between genetic and geographic distances of either the aphid or host plant populations, leading us to reject the isolation-by-distance model as a plausible explanation for the demographic histories of these two species.


Exploratory study of macrophage polarization and spatial distribution in colorectal cancer liver metastasis: a pilot study.
The liver is the most typical site of metastatic disease for patients with colorectal cancer (CRC), and up to half the patients with CRC will develop colorectal liver metastasis (CLM). Studying the tumor microenvironment, particularly macrophages and their spatial distribution, can give us critical insight into treatment. Ten CLMs (five treatment-naïve and five post-neoadjuvant chemotherapy) were stained with multiplex immunofluorescence panels against cytokeratins, CD68, Arg1, CD206, CD86, CD163, PD-L1, and MRP8-14. Densities of cell phenotypes and their spatial distribution in the tumor center and the normal liver-tumor interface were correlated with clinicopathological variables. M2 macrophages were the predominant subtype in both the tumor center and the periphery, with a relatively higher density at the periphery. The larger tumors, more than 3.9 cm, were associated with higher densities of total CD68+ macrophages and CD68+CD163+ CD206neg and CD68+CD206+ CD163neg M2 macrophage subtypes. Total macrophages in the tumor periphery demonstrated significantly greater proximity to malignant cells than did those in the tumor center (p=0.0371). The presence of higher than median CD68+MRP8-14+CD86neg M1 macrophages in the tumor center was associated with poor overall survival (median 2.34 years) compared to cases with lower than median M1 macrophages at the tumor center (median 6.41 years) in univariate analysis. The dominant polarization of the M2 macrophage subtype could drive new therapeutic approaches in CLM patients.


New calix[4]arene derivatives as ionophores in polymeric membrane electrodes for Ag(I): comparative selectivity studies and detection of DNA hybridization.
Four calix[4]arene derivatives containing various donor atoms and different topology (L1-L4) have been synthesized and used as neutral ionophores to fabricate silver ion selective electrodes (Ag-ISEs) which were characterized in terms of their potentiometric selectivities and complex formation constants. The ionophore L2 having two nitrogen and two sulfur donors showed stronger interactions with Ag(+) and the highest selectivity coefficient towards Ag(+). The best membrane electrode was prepared from L2 and used to fabricate silver ion selective microelectrodes (Ag-ISμEs) which could detect silver ions in 1000 μL samples with detection limit around 1 μM using sodium ion microelectrodes as a pseudo reference electrode. Such potentiometric measurement was then applied to detect DNA hybridization on a gold substrate, employing immobilized lipoic acid-modified pyrrolidinyl PNA (Lip-acpcPNA) as a probe. The hybridization between the neutral Lip-acpcPNA probe and DNA target led to a negatively charged surface that could bind positively charged silver nanoparticles (AgNPs(+)) via electrostatic interactions. The hybridization signal was observed by dissolution of the electrostatically adsorbed AgNPs(+) with hydrogen peroxide. Excellent discrimination of complementary from single mismatched and non-complementary DNA targets was achieved under non-stringent conditions. The detection limit of DNA was 0.2 μM in 1000 μL samples.


Testing threshold and hormesis in a random effects dose-response model applied to developmental toxicity data.
Here we describe a random effects threshold dose-response model for clustered binary-response data from developmental toxicity studies. For our model we assume that a hormetic effect occurs in addition to a threshold effect. Therefore, the dose-response curve is based on two components: relationships below the threshold (hormetic u-shaped model) and those above the threshold (logistic model). In the absence of hormesis and threshold effects, the estimation procedure is straightforward. We introduce score tests that are derived from a random effects hormetic-threshold dose-response model. The model and tests are applied to clustered binary data from developmental toxicity studies of animals to test for hormesis and threshold effects. We also compare the score test and likelihood ratio test to test for hormesis and threshold effects in a simulated study.


Vital signs and early warning score monitoring: perceptions of clinical staff about current practices and introducing an electronic rapid response system.
This study investigated clinical staff perceptions of learning about current monitoring practices and the planned introduction of an electronic system for patient monitoring. The aim of this research was to evaluate the perceptions of clinical staff (nurses and doctors) about the perceived strengths and weaknesses of the current state of the rapid response system (RRS) and how those strengths and weakness would be affected by introducing an electronic RRS. This research applied a descriptive study methodology. Two detailed sessions on demonstration on the electronic RRS for measuring and recording vital signs and the electronic Early Warning System (EWS) were followed by two structured surveys administered through an online portal (SurveyMonkey) for nurses and doctors working at Taranaki District Health Board. The study was planned and conducted between October 2020 and May 2021 at Taranaki Base Hospital, New Plymouth, New Zealand. We found that the perceptions of clinical staff were a combination of key practice issues with current manual monitoring, expectations of improved visibility of vital sign charts, better communication between staff and thus improved patient care with the introduction of an electronic system. A majority (24, 60%) of nurses reported that, when called to assess deteriorating patients, the responders arrive at bedside within 5-30 min and an additional 11 (27%) said the responders arrive within 5 min. That is a collective 87% responder arrival within 30 min. Staff believe that an electronic RRS could improve communication, speed up decision making and have a positive impact on patient outcomes.


Slitlamp stretching of the corneal flap after laser in situ keratomileusis to reduce corneal striae.
To examine the efficacy of treating immediate postoperative corneal striae and poor flap alignment by stretching the corneal flap at the slitlamp with a cotton-tip applicator and compare the results using this technique with those using the conventional technique of refloating the flap with balanced salt solution (BSS(R)). TLC Laser Eye Center, Garden City, New York, USA. Charts of 7154 eyes having laser in situ keratomileusis (LASIK) were reviewed retrospectively. During the 11 months prior to January 1, 2000, 3516 eyes had LASIK. Patients with flap striae or a malpositioned flap at the immediate slitlamp evaluation were treated by refloating the flap (Group A). During the 11 months subsequent to January 1, 2000, 3638 eyes had LASIK. Patients with flap striae or a malpositioned flap at the immediate slitlamp evaluation were treated by flap stretching with a cotton-tip applicator (Group B). The number of eyes that required retreatment for flap striae was analyzed. Twenty-nine eyes in Group A (0.82%) required retreatment for visually significant flap striae after day 1, and 11 eyes in Group B (0.30%) required retreatment. A loss of best corrected visual acuity occurred in 3 Group A eyes and 2 Group B eyes. During the immediate postoperative period, stretching the flap with a cotton-tip applicator was a simple, safe, and effective technique for reducing visually significant flap striae. Unlike refloating the flap with BSS, flap stretching at the slitlamp does not require additional anesthesia, exposure time, or dehydration of the ocular surface.


Peripheral blood markers predict immunotherapeutic efficacy in patients with advanced non-small cell lung cancer: A multicenter study.
This study aims to investigate the prognostic impact of peripheral blood markers in patients with advanced non-small cell lung cancer (NSCLC) undergoing immunotherapy. In the current multicenter study, 157 advanced NSCLC cases treated by immunotherapy at three institutions were included. Biochemical parameters in baseline peripheral blood were collected. The associations between biochemical parameters and prognosis were investigated by the Kaplan-Meier survival analyses and Cox regression, and the predictive performances of biomarkers were evaluated via receiver operating characteristic analysis. The neutrophil-to-lymphocyte ratio (NLR) (progression-free survival [PFS]: hazard ratio [HR], 1.766; 95% confidence interval [CI], 1.311-2.380; p < 0.001; overall survival [OS]: HR, 1.283; 95% CI, 1.120-1.469; p < 0.001) and red blood cell distribution width (RDW) (PFS: HR, 1.052; 95% CI, 1.005-1.102; p = 0.031; OS: HR, 1.044; 95% CI, 1.001-1.091; p = 0.042) were revealed as independent predictors for both PFS and OS. In addition, NLR ≥3.79 (1-year PFS, 24.2% [95% CI, 15.2%-38.4%] versus 27.3% [95% CI, 18.2%-41.1%], p = 0.041; 1-year OS, 44.2% [95% CI, 32.5%-60.1%] versus 71.8% [95% CI, 60.6%-85.2%], p < 0.001) or RDW ≥44.8 g/L (1-year PFS, 19.2% [95% CI, 11.4%-32.3%] versus 31.7% [95% CI, 21.9%-46.0%], p = 0.049; 1-year OS, 54.0% [95% CI, 42.7%-68.3%] versus 63.1% [95% CI, 50.6%-78.6%], p = 0.014) was significantly correlated to poorer PFS and OS than NLR < 3.79 or RDW <44.8 g/L. Moreover, NLR and RDW achieved areas under the curve with 0.651 (95% CI, 0.559-0.743) and 0.626 (95% CI, 0.520-0.732) for predicting PFS, and 0.660 (95% CI, 0.567-0.754) and 0.645 (95% CI, 0.552-0.739), for OS. Therefore, PLR and RDW could help predict the immunotherapeutic efficacy of advanced NSCLC.


Pulsed Microwave Liver Ablation: An Additional Tool to Treat Hepatocellular Carcinoma.
This study aimed to analyze the outcomes of HCC patients treated with a novel technique-pulsed microwave ablation (MWA)-in terms of safety, local tumor progression (LTP), intrahepatic recurrence (IHR), and overall survival (OS). A total of 126 pulsed microwave procedures have been performed in our center. We included patients with mono- or multifocal HCC (BCLC 0 to D). The LTP at 12 months was 9.9%, with an IHR rate of 27.8% at one year. Survival was 92.0% at 12 months with 29.4% experiencing post-operative complications (28.6% Clavien-Dindo 1-2, 0.8% Clavien-Dindo 3-4). Stratifying patients by BCLC, we achieved BCLC 0, A, B, C, and D survival rates of 100%, 93.2%, 93.3%, 50%, and 100%, respectively, at one year, which was generally superior to or in line with the expected survival rates among patients who are started on standard treatment. The pulsed MWA technique is safe and effective. The technique can be proposed not only in patients with BCLC A staging but also in the highly selected cases of BCLC B, C, and D, confirming the importance of the concept of stage migration. This procedure, especially if performed with a minimally invasive technique (laparoscopic or percutaneous), is repeatable with a short postoperative hospital stay.


Identification of molecules associated with the development of metastasis in human malignant melanoma.
Differential antibody reactivity has been used to identify molecules which change in expression or which are modified during tumor progression in human malignant melanoma. Such molecules may play a role in the development of the metastatic capacity of this tumor. Two of these molecules (ICAM-1 and MUC18) have been identified as cell adhesion molecules which are potentially involved in tumor-leukocyte-endothelial interactions.


Effect of intestinal microflora suppression on liver carcinogenicity of dimethylnitrosamine in Syrian hamsters.
Liver tumors induced by dimethylnitrosamine showed an increased incidence in Syrian hamsters with intestinal microflora suppressed by antibiotics, as compared with the incidence in animals not treated with antibiotics. The possible mechanisms, including metabolic alterations caused by changes in the normal microflora population, were discussed.


Spontaneous involution of two sinus pericranii - a unique case and review of the literature.
Sinus pericranii is a rare vascular anomaly in which an abnormal communication exists between the extracranial venous system and the dural venous sinuses. The natural history is of increasing size and potential life-threatening complications, including thrombosis and haemorrhage. Thus surgical management is the mainstay of treatment. We present a unique case of spontaneous involution of two sinus pericranii in a 1-year-old patient, the second reported case of spontaneous involution in the literature, and the first in which regression occurred at such a young age. The clinical, diagnostic and management options are discussed.


CD15+ Bone Marrow-derived Cells Are Regulators of Immune Response in ARG1-producing Colorectal Cancer Cells.
Bone marrow-derived cells regulate the antitumor functions of tumor infiltrating lymphocytes (TILs) through arginase 1 (ARG1)-dependent metabolism. This study examines which ARG1-producing lineage is responsible for the inhibitory function of TILs. Multiplexed immunohistochemistry was performed for CD11b, CD163, CD68, and CD15, together with ARG1 expression and CD3+ TIL infiltration estimation in human colorectal cancer specimens. Stratified survival analyses demonstrated that a large number of CD3+ TILs is a favorable prognostic factor in subgroups with a high level of ARG1+ infiltration and in the subgroup with a low level of ARG1- CD15+ infiltration. Calculation of the ARG1+/ARG1- ratio demonstrated that CD3+ TIL infiltration was prognostic in the subgroup with a low ARG1+/ARG1- ratio for CD15+ cells, contrary to other lineages. Tumor infiltrating CD15+ cells, the majority of which show polymorphonuclear features, are responsible for the ARG1-dependent T-cell dysfunction in human colorectal cancer.


A single-molecule RNA electrical biosensor for COVID-19.
The COVID-19 pandemic shows a critical need for rapid, inexpensive, and ultrasensitive early detection methods based on biomarker analysis to reduce mortality rates by containing the spread of epidemics. This can be achieved through the electrical detection of nucleic acids at the single-molecule level. In particular, the scanning tunneling microscopic-assisted break junction (STM-BJ) method can be utilized to detect individual nucleic acid molecules with high specificity and sensitivity in liquid samples. Here, we demonstrate single-molecule electrical detection of RNA coronavirus biomarkers, including those of SARS-CoV-2 as well as those of different variants and subvariants. Our target sequences include a conserved sequence in the human coronavirus family, a conserved target specific for the SARS-CoV-2 family, and specific targets at the variant and subvariant levels. Our results demonstrate that it is possible to distinguish between different variants of the COVID-19 virus using electrical conductance signals, as recently suggested by theoretical approaches. Our results pave the way for future miniaturized single-molecule electrical biosensors that could be game changers for infectious diseases and other public health applications.


Insulin Sensitivity Determines Effects of Insulin and Meal Ingestion on Systemic Vascular Resistance in Healthy Subjects.
In addition to insulin's metabolic actions, insulin can dilate arterioles which increase blood flow to metabolically active tissues. This effect is blunted in insulin-resistant subjects. Insulin's effect on SVR, determined by resistance arterioles, has, however, rarely been examined directly. We determined the effects of both hyperinsulinemia and a mixed meal on SVR and its relationship with insulin sensitivity. Thirty-seven lean and obese women underwent a hyperinsulinemic-euglycemic clamp, and 24 obese volunteers underwent a mixed-meal test. SVR was assessed using CPP before and during hyperinsulinemia as well as before and 60 and 120 minutes after a meal. SVR decreased significantly during hyperinsulinemia (-13%; p < 0.001) and after the meal (-11%; p < 0.001). Insulin decreased SVR more strongly in insulin-sensitive individuals (standardized β: -0.44; p = 0.01). In addition, SVR at 60 minutes after meal ingestion was inversely related to the Matsuda index (β: -0.39; p = 0.04) and the change in postprandial SVR was directly related to postprandial glycemia (β: 0.53; p < 0.01). Hyperinsulinemia and meal ingestion decrease SVR, which is directly associated with metabolic insulin resistance. This suggests that resistance to insulin-induced vasodilatation contributes to regulation of vascular resistance.


Correction: Solid-state electrical applications of protein and peptide based nanomaterials.
Correction for 'Solid-state electrical applications of protein and peptide based nanomaterials' by Sayak Subhra Panda et al., Chem. Soc. Rev., 2018, 47, 3640-3658.


Successful medical group integration: it's about more than the numbers.
Key aspects of integrating a medical group into a health system include: Performing due diligence. Developing a culture of trust. Onboarding new physicians and groups. Dealing with underperforming physicians.


Plasma vasoactive intestinal polypeptide (VIP) levels and intestinal ischaemia.
Vasoactive intestinal polypeptide (VIP) is released into the portal circulation in large quantities by ischaemic bowel. In view of its known high concentration in the gut and potent vasoactive properties it may well be implicated in the pathogenesis of the serious haemodynamic changes produced by gut ischaemia.


A novel coiled-coil domain containing-related gene signature for predicting prognosis and treatment effect of breast cancer.
Breast cancer (BRCA) is a prevalent tumor worldwide. The association between the coiled-coil domain-containing (CCDC) protein family and different tumors has been established. However, the prognostic significance of this protein family in breast cancer remains uncertain. Gene expression and clinical data were obtained from the TCGA, METABRIC, and GEO databases. Prognosis genes were identified using univariate Cox and LASSO Cox regression, leading to the establishment of a prognostic signature. Subsequently, the risk model was conducted based on survival and clinical feature analyses, and a nomogram for prognosis prediction was developed. Furthermore, analyses of biological function, immune characteristics, and drug sensitivity were performed. Finally, single-cell sequencing data were utilized to uncover the expression patterns of genes in the risk model. Five genes were identified and utilized for risk modeling. The model demonstrated excellent prognostic value as indicated by ROC and Kaplan-Meier analysis. The high-risk group exhibited shorter survival time and higher likelihood of recurrence. Functional annotation indicated a correlation between the risk score and immune pathways. Conversely, the low-risk group displayed a greater enrichment in immune pathways and exhibited more active immune microenvironment characteristics. Additionally, drug sensitivity analysis using both public and our sequencing data revealed that the risk model possessed a broad range of predictive values. We have developed a gene signature and have verified that patients with low-risk are more likely to have better prognosis and respond positively to therapy. This finding offers a valuable point of reference for BRCA individualized treatment.


Tissue inhibitor of metalloproteinases. Identification of precursor forms synthesized by human fibroblasts in culture.
Precursor forms of the glycoprotein tissue inhibitor of metalloproteinases (TIMP) synthesized by human fibroblasts in culture have been identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of specific immunoprecipitates. Translation of mRNA extracted from fibroblasts in the cell-free rabbit reticulocyte lysate system yielded a single immunoprecipitable precursor of tissue inhibitor of metalloproteinases, Mr 22000. Intact fibroblasts cultured in the presence of tunicamycin synthesized an Mr 20 000 form of tissue inhibitor of metalloproteinases, detectable intracellularly and extracellularly. This is in contrast to the predominantly intracellular Mr 24 000 form synthesized during monensin treatment of cells and the normal secreted form of tissue inhibitor of metalloproteinases, Mr 29 000. Isoelectric focusing of the various immunoprecipitable precursor forms showed a progressive increase in positive charge and microheterogeneity of the protein during cellular processing. The data suggest that the inhibitor protein core, of basic pI, is glycosylated initially by the addition of mostly neutral sugars and subsequently by acidic sugars, prior to secretion.


Rice life cycle-based global mercury biotransport and human methylmercury exposure.
Protecting the environment and enhancing food security are among the world's greatest challenges. Fish consumption is widely considered to be the single significant dietary source of methylmercury. Nevertheless, by synthesizing data from the past six decades and using a variety of models, we find that rice could be a significant global dietary source of human methylmercury exposure, especially in South and Southeast Asia. In 2013, globalization caused 9.9% of human methylmercury exposure via the international rice trade and significantly aggravated rice-derived exposure in Africa (62%), Central Asia (98%) and Europe (42%). In 2016, 180 metric tons of mercury were generated in rice plants, 14-fold greater than that exported from oceans via global fisheries. We suggest that future research should consider both the joint ingestion of rice with fish and the food trade in methylmercury exposure assessments, and anthropogenic biovectors such as crops should be considered in the global mercury cycle.


Discordance between patient-reported and actual emergency department pain management.
To determine patient knowledge of the nature of their pain management in the ED. This was a planned sub-study of data collected during a randomised, controlled trial of the nature of the informed consent process in a single ED. Patients aged ≥18 years, with a triage pain score of ≥4, were enrolled. Forty-eight hours post-ED discharge, patients were asked if they had declined analgesia or if a range of pain management options had been administered. The primary outcome was discordance between the patient report and the ED report (proportion of cases where these reports differed). Outcome data were collected on 655 patients. There was significant discordance for all variables examined (P < 0.001). Discordance for patients declining analgesia was lowest at 8.9% (95% confidence interval [CI] 6.8-11.4). Discordance for administration of pain management 'other' than analgesia was highest at 32.6% (95% CI 29.0-36.4). Discordance for the administration of oral analgesia or 'any' analgesia was 17.1% (95% CI 14.3-20.3) and 14.4% (95% CI 11.8-17.3), respectively. For both of these outcomes, patients with chest pain and lower triage pain scores were more likely to report discordant responses. With the exception of 'other' pain management, smaller proportions of patients incorrectly reported not receiving management than incorrectly reporting that they did receive it. Patients are often unaware of the nature of their pain management. They are most often unaware of management other than analgesia. Patients with chest pain and lower triage pain scores had the least knowledge of their pain management.


High efficiency Cu2MnSnS4 thin film solar cells with SnS BSF and CdS ETL layers: A numerical simulation.
The quaternary compound copper manganese tin sulfide Cu2MnSnS4 is a potential absorber semiconductor material for fabricating thin film solar cells (TFSC) thanks to their promising optoelectronic parameters. This article numerically investigated the performance of Cu2MnSnS4 (CMTS)-based TFSC without and with tin sulphide (SnS) back surface field (BSF) thin-film layer. First, the impact of several major influential parameters such as the active material's thickness, doping concentration of photoactive materials, density of bulk and interface defect, working temperature, and metal contact, were studied systematically without a BSF layer. Thereafter, the photovoltaic performance of the optimized pristine cell was further investigated with an SnS as BSF inserted between the absorber (CMTS) with a Platinum back metal of an optimized heterostructure of Cu/ZnO:Al/i-ZnO/n-CdS/p-Cu2MnSnS4/Pt. Thus, the photoconversion efficiency (PCE) of 25.43% with a J SC of 34.41nullmA/cm2 and V OC of 0.883 V was achieved under AM1.5G solar spectrum without SnS BSF layer. Furthermore, an improved PCE of 31.4% with a J SC of 36.21nullmA/cm2 and V OC of 1.07 V was achieved with a quantum efficiency of over 85% in the wavelengths of 450-1000 nm by the addition of SnS BSF layer. Thus, this obtained systematic and consistent outcomes reveal immense potential of CMTS with SnS as absorber and BSF, respectively and provide imperious guidance for fabricating highly a massive potential efficient solar cell.


Effect of hypobaric hypoxia on slow- and fast-growing chickens fed diets with high and low protein levels.
The occurrence of pulmonary hypertension syndrome in fast-growing broiler chickens and slow-growing leghorns was studied. In two similar trials, broiler chickens and white leghorns were placed either at low altitude (295 m) or in hypobaric chambers (simulated high altitude of 2054 m) and fed either a high- (22%) or low-protein (17%) ration. Right ventricular hypertrophy as measured by right-ventricle:total-ventricle (RV:TV) weight ratio was used as an indicator of pulmonary hypertension. The leghorns did not develop pulmonary hypertension as the result of polycythemia induced by simulated high altitude. Compared with low-altitude broilers and leghorns, broilers reared at high altitude responded with significantly higher hematological values and 56% ascites mortality because of right ventricular failure from pulmonary hypertension, as measured by an increased RV:TV ratio.


Observation of curative effect on meridian theory-based extracorporeal shock wave therapy for non-specific low back pain: study protocol for a randomized controlled trial.
Non-specific low back pain (NLBP) is a major global socioeconomic burden, and the prevalence of NLBP is still on the rise. At present, there is no ideal drug to cure this disease. This may be the reason why patients often use complementary therapies. Among them, extracorporeal shock wave therapy (ESWT) has gradually received more attention and has become the main treatment method for NLBP. The purpose of this study is to provide scientific evidence for the effect and safety of meridian theory-based ESWT on NLBP. This study aims to evaluate the effect and safety of meridian theory-based ESWT on NLBP. This study will also provide more high-quality experimental evidence for the clinical application of meridian theory-based ESWT for the treatment of NLBP in future. The study design is a single-blind, multi-center, randomized controlled trial. 66 patients with NLBP, aged 18 to 60 years, will be randomly divided into two groups: the experimental group (N = 33), which will receive meridian theory-based ESWT application, and the control group (N = 33) which will receive conventional ESWT treatment. These two applications will be carried out twice a week for two weeks. The primary outcome will be the Visual Analog Scale (VAS), and the secondary outcomes will be Oswestry Disability Index (ODI), Surface Electromyography (sEMG), and Patient Health Questionnaire-15 (PHQ-15). All outcomes will be evaluated at baseline and after the intervention (7 days, 14 days). Results of this trial will contribute to providing rigorous clinical evidence for the efficacy and security of meridian theory-based ESWT for NLBP. Chinese Clinical Trial Registry, ChiCTR2100051049. Registered on 10 September 2021, http://www.chictr.org.cn/showproj.aspx?proj=46316 .


Approaches for Effective Clinical Application of Stem Cell Transplantation.
This review highlights problems related to translation of advanced therapy medicinal products (ATMPs) from bench to bedsite. Regenerative medicine within the current regulatory frame reveals common hitches in the course of development, translation, and clinical application. This paper suggests outlining a path from the few examples of successfully approved vs unsuccessful advanced therapies. In the multitude of ongoing studies, few of them achieved positive results with a final treatment available to patients; this result was possible due to multidisciplinary teams working together from the beginning of the development and during the hard route to standardization and clinical application. The root of success of an advanced therapy requires not only the inescapable scientific and biological knowledge but also requires several contributions as regulatory, ethical, medical, and bio-engineering expertise, from the real beginning. A strong scientific rationale and an integrated network of expertises would contribute to a successful investment of available resources in advanced therapy medicinal products and to a greater confidence in future medicine.


Joint effects of enzymatic and high-intensity ultrasonic on the emulsifying propertiesof egg yolk.
This study investigated the joint effect of the enzymatic and high-intensity ultrasonic (HIU) treatments on the emulsifying and structural properties of egg yolk (EY). The evaluation was performed under different HIU powers (i.e., 0, 240, and 480 W) and for different durations (10, 20, and 30 min). Results reveal that the emulsification activity and emulsification capacity at 240 W for 10 min significantly increase than that of the samples without HIU treatment (P < 0.05). The thermal stability reached a maximum of 90.33% in 480 W + 30 min. The HIU treatment under low power and for a short time (240 W + 10 min) reduced the average particle size of the EY to 224.77 nm. The combined treatment produced high zeta potential and total sulfhydryl contents. The highest hydrophobicity was 111.49 μg at 240 W for 20 min. The joint treatment enhanced the hardness and cohesiveness of the EY. Moreover, the α-helix content significantly decreased from 37.13% to 25.02% after the enzymatic treatment, while the β-sheet content increased with time in the 240 W treatment. The G' and G″ curves show an increasing tendency, and the highest G' and G″ were obtained in the 240 W + 30 min group, which is consistent with the dense microstructure. These results reveal that the combined treatment can improve the emulsifying characteristics, which could influence the structural properties of EY, expanding its application in the food industry.


Decreases in the numbers of peripheral blood regulatory T cells, and increases in the levels of memory and activated B cells, in patients with active eosinophilic granulomatosis and polyangiitis.
Eosinophilic granulomatosis with polyangiitis (EGPA), a rare disease characterized by the presence of allergic granulomatosis and necrotizing vasculitis, is often effectively treated with corticosteroids. However, relapse rates are high and, for unknown reasons, some EGPA patients suffer frequent relapses after entry into initial remission. Regulatory T (Treg) cells and B cells are implicated in the development and progression of EGPA. Here, we explored the influence of Treg cells and a co-stimulatory factor present on B cells on the development and course of EGPA. We studied 45 EGPA patients (19 of whom experienced frequent relapses and 26 of whom seldom relapsed) and 67 (control) patients with general asthma. We determined the counts or percentages of whole-blood cells exhibiting the following characteristics: FOXP3(+) cells among CD4(+) Treg cells; CTLA-4(+) cells among CD4(+)/CD25(+) Treg cells; and CD27(+), CD80(+), CD86(+), or CD95(+) cells among CD19(+) B cells. We also measured serum IgG concentrations. Compared with patients with asthma or seldom-relapsing EGPA, frequently relapsing EGPA patients with active disease exhibited decreased counts of Treg cells and increased percentages of B cells that scored as CD80(+), CD27(+), or CD95(+). Patients with frequently relapsing EGPA had increased percentages of CD27(+) and CD95(+) B cells, and fewer CD19(+) B cells, than did patients in the other two groups. Lower CD19(+) B cell counts were associated with reduced Treg cell counts and a lower serum IgG concentration. In patients with frequently relapsing EGPA, decreases in Treg cell numbers and increased percentages of activated B cells may induce apoptosis of B cells.


Persistent shunt dependency in children treated with CSF diversion for idiopathic intracranial hypertension (IIH).
Long-term shunt dependency rates in children treated for IIH with CSF diversion have not been established. We therefore present our experience with 4 children shunted for Idiopathic Intracranial Hypertension (IIH) during the years 1988-2000 with very long-time follow-up. Two out of these patients have experienced late or very late episodes of severe shunt failure during the second or third decade after initial shunt treatment. They were all boys and may not be representative for IIH patients as a whole. Two of them appear, however, to be permanently shunt dependent, indicating that long-term shunt dependency in children treated for IIH with CSF diversion may be more common than previously expected.


Efficient, single-step access to imidazo[1,5-a]pyridine n-heterocyclic carbene precursors.
The three-component coupling reaction of substituted picolinaldehydes, amines, and formaldehyde to produce imidazo[1,5-a]pyridinium ions is reported, providing an efficient method for the preparation of N-heterocyclic carbenes (NHCs). Reactions proceed in high yields under mild conditions, allowing the incorporation of diverse functionality and chiral substituents. Higher order condensations are also described that provide access to multidentate NHC ligands useful for a variety of applications.


Developmental treatment with difluoromethylornithine has few effects on behavior or body weight in Sprague-Dawley rats.
Developmental difluoromethylornithine (DFMO) treatment reduces cerebellar weight [Neuroscience 17 (1986) 399, Neurotoxicol. Teratol. 22 (2000) 415, Behav. Brain Res. 126 (2001) 135], but the functional alterations resulting from this have been little investigated. Here, Sprague-Dawley rats were subcutaneously injected with 500 mg/kg DFMO on postnatal days (PNDs) 5-12 and a comprehensive set of behavioral assessments measured early developmental behaviors (righting reflex, negative geotaxis), motor coordination, acoustic startle, short- and long-term activity, social behaviors, anxiety, and spatial learning and memory. DFMO treatment appeared to cause a decreased latency to perform the negative geotaxis behavior on PNDs 8-10 and increased latency to hang by the forelimbs on PNDs 12-14. Our previous study did not indicate similar effects, but age at testing differed between the two studies. DFMO treatment caused a decreased latency to maximum acoustic startle response in both the acoustic startle paradigm and in the pulse-alone trials of the prepulse inhibition test. This DFMO treatment paradigm induced a 10% decrease in adult cerebellar weight [Behav. Brain Res. 126 (2001) 135], but the results here imply that such developmental stunting has few functional alterations.


(E)-1-[2-(Methyl-sulfan-yl)phen-yl]-2-({(E)-2-[2-(methyl-sulfan-yl)phen-yl]hydrazinyl-idene}(nitro)-meth-yl)diazene.
In the title compound, C(15)H(15)N(5)O(2)S(2), the phenyl rings make dihedral angles of 4.03 (4) and 9.77 (5)° with the plane defined by the central N-N-C-N-N atoms (r.m.s. deviation = 0.010 Å). The C-S-C-C torsion angles of the methyl-sulfanyl groups with their respective phenyl rings are -7.47 (13) and -72.07 (13)°. The shortest centroid-centroid distance of 3.707 Å occurs between the two π-systems N-N-C-N-N and the benzene ring in the diazene 1-position. The H atom bound to the N atom is involved in intra-molecular N-H⋯N and N-H⋯S contacts, while the nitro O atoms are involved in inter-molecular C-H⋯O contacts.


Identification of the 5' regulatory elements of avian lipoprotein lipase gene: synergistic effect of multiple factors.
The organization of cis-acting regulatory elements of the chicken lipoprotein lipase gene was investigated in 5.4 kb of 5' flanking sequences. Various lengths of 5' flanking sequence were linked to the bacterial chloramphenicol acyltransferase (CAT) gene and transfected into primary cultures of chicken adipocytes by DEAE-dextran transfection method. Negative elements are present between -1947 and -139 of the 5' flanking sequence. Removal of these sequences revealed the presence of positive elements located within 138 bp upstream of the major transcription start site. Sequence analysis showed that the region from the major transcription start site to -138 contains an inverted GC box (ACCACGCCCC), a CCAAT element and two direct repeats of the octamer motif, ATTTGCAT. DNase I footprinting assays using a probe extending from -175 to +191, identified three sites protected by nuclear factors. Site I (-126 to -123), a C-rich sequence, GCCC, was identified only on the coding strand. Site II covered the sequence from -95 to -68 and includes the GC box. Site III, from -53 to -26, contained two octamer repeats. Site I is the 5' portion of a 10 bp sequence (CCCTCCCCCC; -126/-116) which is perfectly conserved in the avian and the human promoter. Single or multiple copies of a 37 bp DNA fragment (-138/-102) containing the 10 bp conserved sequence were cloned into LPLCAT-51, upstream or downstream of the major transcription start site and in both orientations; transfection and CAT activity assays with these constructs indicate that the -138/-102 fragment has an enhancer like activity. Additional 5' and internal deletions of LPLCAT-138 suggest that the factors binding to the C-rich element, the GC box and the two octamer repeats have a synergistic effect on promoter activity.


Estimation of the proton affinity values of fifteen matrix-assisted laser desorption/ionization matrices under electrospray ionization conditions using the kinetic method.
The kinetic method, which is known to be simple, fast and precise, is used for the measurement of proton affinity values of fifteen selected matrix-assisted laser desorption/ionization matrices under electrospray ionization conditions. The stabilization of [M - H](-)/[M + Matrix - H](-) ions for beta-cyclodextrin in negative ion mode has been rationalized based on the proton affinity values of the matrices.


Epoxidation of 1,7-octadiene by Pseudomonas oleovorans: fermentation in the presence of cyclohexane.
A very efficient conversion of 1,7-octadiene to 7,8-epoxy-1-octene and 1,2-7,8-diepoxyoctane was achieved by incorporating a high concentration of cyclohexane into the conventional fermentation medium. In the presence of cyclohexane, a 90-ml% conversion of substrate to product was accomplished within 72 h, compared with an 18,5-mol% conversion in the absence of cyclohexane. Furthermore, the products were simultaneously separated and concentrated in the organic phase.


String analysis and energy minimization in the partition of DNA sequences.
Two approaches to the understanding of biological sequences are confronted. While the recognition of particular signals in sequences relies on complex physical interactions, the problem is often analysed in terms of the presence or absence of literal motifs (strings) in the sequence. We present here a test-case for evaluating the potential of this approach. We classify DNA sequences as positive or negative depending on whether they contain a single melted domain in the middle of the sequence, which is a global physical property. Two sets of positive "biological" sequences were generated by a computer simulation of evolutionary divergence along the branches of a phylogenetic tree, under the constraint that each intermediate sequence be positive. These two sets and a set of random positive sequences were subjected to pattern analysis. The observed local patterns were used to construct expert systems to discriminate positive from negative sequences. The experts achieved 79% to 90% success on random positive sequences and up to 99% on the biological sets, while making less than 2% errors on negative sequences. Thus, the global constraints imposed on sequences by a physical process may generate local patterns that are sufficient to predict, with a reasonable probability, the behaviour of the sequences. However, rather large sets of biological sequences are required to generate patterns free of illegitimate constraints. Furthermore, depending upon the initial sequence, the sets of sequences generated on a phylogenetic tree may be amenable or refractory to string analysis, while obeying identical physical constraints. Our study clarifies the relationship between experts' errors on positive and negative sequences, and the contributions of legitimate and illegitimate patterns to these errors. The test-case appears suitable both for further investigations of problems in the theory of sequence evolution and for further testing of pattern analysis techniques.


Directed forgetting in high-functioning adults with autism spectrum disorders.
Rehearsal strategies of adults with autism spectrum disorders (ASDs) and demographically matched typically developed (TD) adults were strategically manipulated by cueing participants to either learn, or forget each list word prior to a recognition task. Participants were also asked to distinguish between autonoetic and noetic states of awareness using the Remember/Know paradigm. The ASD group recognised a similar number of to-be-forgotten words as the TD group, but significantly fewer to-be-learned words. This deficit was only evident in Remember responses that reflect autonoetic awareness, or episodic memory, and not Know responses. These findings support the elaborative encoding deficit hypothesis and provide a link between the previously established mild episodic memory impairments in adults with high functioning autism and the encoding strategies employed.


Enhancing the developmental appropriateness of treatment for depression in youth: integrating the family in treatment.
Treatment models for youth depression that emphasize interpersonal functioning, particularly family relationships, may be particularly promising. This article first reviews the current state of knowledge on the efficacy of psychosocial treatments for depression in youth, with an emphasis on family involvement in treatment. It then discusses developmental factors that may impact the applicability and structure of family-focused treatment models for preadolescent and adolescent youth. Finally, two family-based treatment models that are currently being evaluated in randomized clinical trials are described: one focusing on preadolescent depressed youth and the other on adolescents who have made a recent suicide attempt.


Influence of suspending media upon the susceptibility of Pseudomonas aeruginosa NCTC 6750 and its spheroplasts to polymyxin B.
The lytic and bactericidal actions of polymyxin B on whole cells and spheroplasts of Pseudomonas aeruginosa varied markedly with the suspending media, and there was little correlation between them. Relative rates of lysis of these preparations and also of Bacillus megaterium protoplasts suggested that polymyxin causes progressive damage to the cytoplasmic membrane, such that membrane permeability towards various ions increased as follows: K(+) > Na(+) > NO(3) (-) > Cl(-), Ca(2+), H(2)PO(4) (-)/HPO(4) (2-). Impermeant compounds, such as NaCl and sucrose, protected whole cells against lysis but not against death. It is suggested that lysis of whole cells by polymyxin is a secondary effect, resulting from entry of solutes normally excluded by the cytoplasmic membrane and the fragility of the damaged outer membrane. Because the degree of lysis varies with the external solutes, it should be treated with caution as a descriptor of polymyxin activity.


Growth During Infancy After Extremely Preterm Birth: Associations with Later Neurodevelopmental and Health Outcomes.
To evaluate associations between changes in weight, length, and weight/length ratio during infancy and outcomes later in life among individuals born extremely preterm. Among participants in the Extremely Low Gestational Age Newborn (ELGAN) study, we measured weight and length at discharge from the neonatal intensive care unit (NICU) and at age 2 years and evaluated neurocognitive, psychiatric, and health outcomes at age 10 years and 15 years. Using multivariable logistic regression, we estimated associations between gains in weight, length, and weight/length ratio z-scores between discharge and 2 years and outcomes at 10 and 15 years. High gain was defined as the top quintile of change; low gain, as the bottom quintile of change. High gains in weight and weight/length were associated with greater odds of obesity at 10 years, but not at 15 years. These associations were found only for females. High gain in length z-score was associated with lower odds of obesity at 15 years. The only association found between high gains in growth measures and more favorable neurocognitive or psychiatric outcomes was between high gain in weight/length and lower odds of cognitive impairment at age 10 years. During the 2 years after NICU discharge, females born extremely preterm with high gains in weight/length or weight have greater odds of obesity at 10 years, but not at 15 years. Infants with high growth gains in the 2 years after NICU discharge have neurocognitive and psychiatric outcomes in middle childhood and adolescence similar to those of infants with lower gains in weight and weight/length.


Role of microtubules in the cytoplasmic compartmentation of neurons.
We have examined the role of microtubules (MTs) in the development and maintenance of the cytoplasmic compartmentation of ribosomes in cultured embryonic chick sensory neurons. Control neurons show a sharp cytoplasmic demarcation between the ribosome-rich/MT-deficient 'translational' cytoplasm of the perikaryon and the ribosome-deficient/MT-rich 'expressional' cytoplasm of the axon-like neurites. Neurites treated with 1.0 microgram/ml nocodazole for 15-20 min show in addition to the depolymerization of MTs a clear loss of the cytoplasmic demarcation between the soma and neurite. We found a decreasing density of ribosomes with increasing distance from the soma in the nocodazole treated neurites. Ribosomes, as confirmed by their diameter and sensitivity to ribonuclease treatment, populated the first 100 microns of neurites at roughly the same density as found in the soma (150-300 ribosomes per microns2 in 50 mm longitudinal thin sections). The second 100 microns contained a lower density of ribosomes than the first, 20-60 per microns2, but still higher than controls. Distances past 200 microns were devoid of unambiguous ribosomes. Neurites amputated between 50 and 150 microns from the soma then treated with nocodazole contained a dense population of ribosomes in the proximal segment still attached to the soma, but few or none in the distal segment. We interpret these findings as evidence that ribosomes are able to move from the soma down the neurite after MT disassembly.(ABSTRACT TRUNCATED AT 250 WORDS)


Burden of unmet health-related social needs in an academic adult primary care practice in San Francisco California.
Unmet health-related social needs can influence health outcomes and increase healthcare utilization. There is growing interest in integrating social needs care into healthcare delivery. We conducted an assessment of health-related social needs in an academic adult primary care practice in San Francisco, California. We recruited a random convenience sample of adult English-, Chinese- or Spanish-speaking patients from clinic waiting rooms at the study sites to complete a self-administered, anonymous survey. We used the Accountable Health Communities Health-Related Social Needs Screening Tool for these domains: housing instability, food insecurity, transportation problems, utility help needs, interpersonal safety, financial strain, and family/community support. We conducted univariate and multivariate analyses adjusting for age, sex and survey language. 679 patients completed the survey. Respondents were 57% female and mean age of 58 ± 18 years old. 54% of patients had at least one unmet health-related social need. The most prevalent health-related social needs were financial strain (35%), at least one issue with housing conditions (27%), and food insecurity (23%). Respondents completing the survey in Spanish had significantly higher odds of reporting food insecurity (AOR 3.97, 95%CI 1.86, 8.46), transportation problems (AOR 3.13, 95%CI 1.32, 7.43), and need for support with activities of daily living (AOR 4.58, 95%CI 2.04, 10.25) than respondents completing the survey in English. The burden of unmet health-related social needs was considerable in this adult primary care practice. These findings can support a case for integrating health-related social need screening and social care in the delivery of primary care in the United States to advance health equity.


On the effects of iron ore tailings micro/nanoparticles in embryonic and larval zebrafish (Danio rerio).
Iron ore tailings (IOT) represent a major problem in the mining industry worldwide due to large volumes of waste disposed in mine sites. IOT are exposed to the environment and subjected to wind and water dispersion, even under non-catastrophic scenarios as dam collapses, and the effects of these particles to the biota are still mostly unknown. This work aimed to prepare and to characterize a suspension containing the finest (micro/nano range) particles of IOT and to evaluate its effects on development and behavior of zebrafish (Danio rerio), at both embryonic and larval stages. IOT suspension comprised 37 mg L-1 of a multi-mineral material mainly composed by hematite and quartz, in a size-range of 33-1400 nm. Regarding in vivo toxicological assays, no robust alterations were recorded in functional, morphological and behavioral end-points analyzed, although a significant adhesion of IOT particles on zebrafish chorion was observed, without a prejudice of embryo hatching. Under applied conditions, iron ore particles did not present harmful effects to the initial stages of zebrafish development, and the particle size range and potential interactions with SiO2 content might be behind such effect.