Persistent hyperinsulinaemic hypoglycaemia in infancy.
Persistent hyperinsulinaemic hypoglycaemia in infancy (PHHI) is a heterogeneous condition characterised by unregulated insulin secretion in response to a low blood glucose level. It is the most common cause of severe and persistent hypoglycaemia in neonates. It is extremely important to recognise this condition early and institute appropriate management to prevent significant brain injury leading to complications like epilepsy, cerebral palsy and neurological impairment. Histologically, PHHI is divided mainly into three types-diffuse, focal and atypical disease. Fluorine-18-l-3,4-dihydroxyphenylalanine positron emission tomography (18F-DOPA-PET/CT) scan allows differentiation between diffuse and focal diseases. The diffuse form is inherited in an autosomal recessive (or dominant) manner whereas the focal form is sporadic in inheritance and is localised to a small region of the pancreas. The molecular basis of PHHI involves defects in key genes (ABCC8, KCNJ11, GCK, SLC16A1, HADH, UCP2, HNF4A and GLUD1) that regulate insulin secretion. Focal lesions are cured by lesionectomy whereas diffuse disease (unresponsive to medical therapy) will require a near-total pancreatectomy with a risk of developing diabetes mellitus and pancreatic exocrine insufficiency. Open surgery is the traditional approach to pancreatic resection. However, recent advances in laparoscopic surgery have led to laparoscopic near-total pancreatectomy for diffuse lesions and laparoscopic distal pancreatectomy for focal lesions distal to the head of the pancreas.


Diagnosis and management of infantile marfan syndrome.
Marfan syndrome is infrequently diagnosed early in infancy. The experience of the authors with 22 severely affected infants diagnosed as having Marfan syndrome in the first 3 months of life is described and the literature on 32 additional infants with Marfan syndrome is reviewed. It was found that serious cardiac pathology (82% of the patients described in the article, 94% of those described in the literature) may be present at birth, and that congenital contractures (64% of our cases, 47% of literature cases) are often an associated finding. Other useful clinical findings included arachnodactyly, dolichocephaly, a characteristic facies, a high-arched palate, micrognathia, hyperextensible joints, pes planus, anterior chest deformity, iridodenesis, megalocornea, and dislocated lenses. Echocardiography was useful as a noninvasive method for defining the extent of cardiovascular involvement and following its course. Characteristic cardiac findings in early life included mitral valve prolapse, valvular regurgitation, and aortic root dilation. Cardiac function ranged from normal to poor, with a tendency to worsen. Of the 22 cases 3 infants died during the first year of life. Morbidity and mortality may be high when Marfan syndrome is diagnosed during infancy, and prompt recognition of this phenotype can facilitate management and counseling. Most such severe cases appear to be due to a sporadic mutation in a single germ cell of one parent. Many familial cases may have milder manifestations, be more difficult to detect during infancy, and have a better prognosis.


Prospective evaluation of sedation-related adverse events in pediatric patients ventilated for acute respiratory failure.
Sedation-related adverse events in critically ill pediatric patients lack reproducible operational definitions and reference standards. Understanding these adverse events is essential to improving the quality of patient care and for developing prevention strategies in critically ill children. The purpose of this study was to test operational definitions and estimate the rate and site-to-site heterogeneity of sedation-related adverse events. Prospective cohort study. Twenty-two pediatric intensive care units in the United States enrolling baseline patients into a prerandomization phase of a multicenter trial on sedation management. Pediatric patients intubated and mechanically ventilated for acute respiratory failure. Analysis of adverse event data using consistent operational definitions from a Web-based data management system. There were 594 sedation-related adverse events reported in 308 subjects, for a rate of 1.9 adverse events per subject and 16.6 adverse events per 100 pediatric intensive care unit days. Fifty-four percent of subjects had at least one adverse event. Seven (1%) adverse events were classified as severe, 347 (58%) as moderate, and 240 (40%) as mild. Agitation (30% of subjects, 41% of events) and pain (27% of subjects, 29% of events) were the most frequently reported events. Eight percent of subjects (n = 24) experienced 54 episodes of clinically significant iatrogenic withdrawal. Unplanned endotracheal tube extubation occurred at a rate of 0.82 per 100 ventilator days, and 32 subjects experienced postextubation stridor. Adverse events with moderate intraclass correlation coefficients included: Inadequate sedation management (intraclass correlation coefficient = 0.130), clinically significant iatrogenic withdrawal (intraclass correlation coefficient = 0.088), inadequate pain management (intraclass correlation coefficient = 0.080), and postextubation stridor (intraclass correlation coefficient = 0.078). Operational definitions for sedation-related adverse events were consistently applied across multiple pediatric intensive care units. Adverse event rates were different from what has been previously reported in single-center studies. Many adverse events have moderate intraclass correlation coefficients, signaling site-to-site heterogeneity.


Stretch-dependent activation and desensitization of mitogen-activated protein kinase in carotid arteries.
Arterial smooth muscle stretch is an important physiological modulator of vascular function. To identify intracellular processes altered during muscle stretch, we found previously that extracellular signal-regulated kinase-mitogen-activated protein kinase (MAPK) activity increased in response to the application of mechanical loads. In the present study, stretch-dependent activation of MAPK in porcine carotid arteries was investigated as was the phosphorylation of the thin filament-binding protein caldesmon, which is known to be a substrate for the kinase in fully differentiated smooth muscle. MAPK activity was 67 pmol.min-1.mg protein-1 in unloaded muscle strips immediately after attachment to force transducers and 139 pmol.min-1.mg protein-1 within 30 s of muscle stretch. When muscle strips were continually stretched, MAPK activity remained elevated for approximately 2 h and then decreased over 16 h to 16 pmol.min-1.mg protein-1. When muscle strips were stretched and then unloaded, MAPK activity decreased within 1 h to the level present in the muscle before the stretch. These effects of muscle stretch on MAPK activity were additive to the effects of KCl or phorbol ester stimulation and were partially inhibited by reducing extracellular Ca2+. Eliminating extracellular Ca2+ had no effect on phorbol 12,13-dibutyrate (PDBu)-dependent contractions or MAPK activity; however, KCl-dependent contractions and MAPK activity were completely abolished by this procedure. An antibody specific for detecting caldesmon phosphorylated by MAPK, vs. protein kinase C (PKC), was developed and used to assess relative caldesmon phosphorylation in unstimulated and PDBu-stimulated muscle strips. In all cases investigated, the level of MAPK activity correlated with phosphocaldesmon immunoreactivity. Because arterial MAPK activity is regulated by PKC- and stretch-dependent mechanisms, these data are consistent with a role for MAPK and the subsequent phosphorylation of caldesmon as mediators in the stretch activation of vascular smooth muscle.


Application of microcurrents of bioresonance and transdermal delivery of active principles in lymphedema and lipedema of the lower limbs: a pilot study.
Application of microcurrents of bioresonance may allow protein aggregates lysis and a related enhancement of lymphatic drainage. Combining bioresonance with transcutaneous passage of active principles, by means of skin electroporation, microcirculation and clearance of connective tissues may be theoretically activated. A pilot study on an electro-medical device which includes these two technologies (Transponder(®)), has been performed on patients affected by lymphedema (LYM) and/or lipedema (LIP) of the lower limbs. Eight patients affected by primary or secondary unilateral LYM or LIP were submitted to six consecutive daily sessions with the medical device; the first two sessions were performed by a trained physiotherapist, whilst the following four sessions were self-administered by the patients themselves at home (who were educated about the technique). Magnesium silicate was delivered transcutaneously by means of the device at each session. Pre-post-treatment assessment included: 1) limb volumetry by means of tape measurement; 2) segmental multifrequency bioimpedance spectroscopy for fluid changes, with L-DEX measurement; 3) visual analogue scale (VAS) (0-10 score) questionnaire for related symptoms. All the patients completed the scheduled treatment. After the treatment the mean volume of the whole limb decreased from 9462.85 (±3407.02) to 9297.37 cc (±3393.20), which accounts for a 165.48 cc (2%) reduction after six days of treatment. The pre/post-treatment VAS mean score changes were: heaviness from 4.57±3.46 to 2.43±2.57 (-47%), dysesthesias from 1.71±2.63 to 0.71±1.50 (-58%), pain from 1.57±2.57 to 0.57±0.79 (-64%). Diuresis VAS measurement passed from 7.43±1.81 to 8.57±0.98 (15% increase). The average L-DEX percentage reduction was 21%. No side effects were reported and a good patients' compliance was recorded. The preliminary data of this pilot study show that the combination of microcurrents of bioresonance with transdermal delivery of active principles indicate that it could result in edema decrease and symptom improvement in patients affected by LYM and/or LIP of the lower limbs. Self-administered modality of the electrical device is possible and effective; no side effects have been reported.


MultiMAP: dimensionality reduction and integration of multimodal data.
Multimodal data is rapidly growing in many fields of science and engineering, including single-cell biology. We introduce MultiMAP, a novel algorithm for dimensionality reduction and integration. MultiMAP can integrate any number of datasets, leverages features not present in all datasets, is not restricted to a linear mapping, allows the user to specify the influence of each dataset, and is extremely scalable to large datasets. We apply MultiMAP to single-cell transcriptomics, chromatin accessibility, methylation, and spatial data and show that it outperforms current approaches. On a new thymus dataset, we use MultiMAP to integrate cells along a temporal trajectory. This enables quantitative comparison of transcription factor expression and binding site accessibility over the course of T cell differentiation, revealing patterns of expression versus binding site opening kinetics.


Phase I study of dovitinib (TKI258), an oral FGFR, VEGFR, and PDGFR inhibitor, in advanced or metastatic renal cell carcinoma.
Signaling through the fibroblast growth factor (FGF) pathway may account for tumor resistance to antiangiogenic therapies targeting the VEGF pathway. Here, dovitinib (TKI258), a potent oral inhibitor of FGF receptor, VEGF receptor (VEGFR), and platelet-derived growth factor receptor tyrosine kinases, is studied in a dose escalation trial. Patients with advanced or metastatic renal cell carcinoma (RCC) with predominant clear cell histology were treated with oral dovitinib 500 or 600 mg/day (5-days-on/2-days-off schedule). Twenty heavily pretreated patients (median 3 prior regimens) were enrolled, with 16, 11, and 12 patients having previously received at least 1: VEGFR inhibitor, mTOR inhibitor, and immunotherapy, respectively. Fifteen and 5 patients were treated in 500- and 600-mg cohorts, respectively. Three patients experienced dose-limiting toxicities: grade 2 bradycardia (500 mg), grade 4 hypertensive crisis (600 mg), and grade 3 asthenia with grade 2 nausea and vomiting (600 mg). The most common adverse events related to dovitinib were nausea (75%), diarrhea (70%), vomiting (70%), and asthenia (50%), the majority of which were mild (grade 1 or 2), with grade 3 events 5% or less (except asthenia, 15%) and only one grade 4 event (hypertensive crisis). Two patients achieved a partial response (500 mg), and 12 patients had stable disease, including 2 patients with long lasting disease stabilizations (>1 year) in the 500-mg cohort. Dovitinib was tolerable and showed antitumor activity at a maximum tolerated dose of 500 mg on a 5-days-on/2-days-off schedule in heavily pretreated RCC patients.


Prevalence and genome characteristics of canine astrovirus in southwest China.
The aim of this study was to investigate canine astrovirus (CaAstV) infection in southwest China. We collected 107 faecal samples from domestic dogs with obvious diarrhoea. Forty-two diarrhoeic samples (39.3 %) were positive for CaAstV by RT-PCR, and 41/42 samples showed co-infection with canine coronavirus (CCoV), canine parvovirus-2 (CPV-2) and canine distemper virus (CDV). Phylogenetic analysis based on 26 CaAstV partial ORF1a and ORF1b sequences revealed that most CaAstV strains showed unique evolutionary features. Interestingly, putative recombination events were observed among four of the five complete ORF2 sequences cloned in this study, and three of the five complete ORF2 sequences formed a single unique group, suggesting that these strains could be a novel genotype. We successfully sequenced the complete genome of one CaAstV strain (designated 2017/44/CHN), which was 6628 nt in length. The features of this genome include putative recombination events in the ORF1a, ORF1b and ORF2 genes, while the ORF2 gene had a continuous insertion of 7 aa in region II compared with the other complete ORF2 sequences available in GenBank. Phylogenetic analysis showed that 2017/44/CHN formed a single group based on genome sequences, suggesting that this strain might be a novel genotype. The results of this study revealed that CaAstV circulates widely in diarrhoeic dogs in southwest China and exhibits unique evolutionary events. To the best of our knowledge, this is the first report of recombination events in CaAstV, and it contributes to further understanding of the genetic evolution of CaAstV.


Tai chi-muscle power training for children with developmental coordination disorder: a randomized controlled trial.
This study compared the effectiveness of tai chi (TC) muscle power training (MPT), TC alone, MPT alone, and no training for improving the limits of stability (LOS) and motor and leg muscular performance and decreasing falls in children with developmental coordination disorder (DCD). One hundred and twenty-one children with DCD were randomly assigned to the TC-MPT, TC, MPT, or control group. The three intervention groups received TC-MPT, TC, or MPT three times per week for 3 months. Measurements were taken before and after the intervention period. The primary outcomes were the LOS completion time and dynamic LOS scores. The secondary outcomes included the Movement Assessment Battery for Children-Second Edition total test score and percentile rank, knee muscle peak force and time to peak force, and the number of falls. None of the interventions affected the LOS test scores. Improvements in the peak forces of the knee extensors and flexors were demonstrated in the TC (p = 0.006) and MPT groups (p = 0.032), respectively. The number of falls also decreased in these two groups (p < 0.001). Thus, clinicians may prescribe TC or MPT for children with DCD to increase their knee muscle strength and reduce their risk of falls.


Gait analysis before and after gastrocnemius fascia lengthening in children with cerebral palsy.
Equinus deformity is a common problem in children with spastic cerebral palsy (CP). Persistent deformity that interferes with function is treated by surgically lengthening the triceps surae. Surgical approaches carry a recurrence risk of equinus deformity or over correction with the development of calcaneal deformity, crouch and diminished strength for push-off during gait. These aspects interfere with the basic function of the gastrocnemius/soleus complex. This study aimed to analyze kinematic and kinetic effects of gastrocnemius fascia lengthening on gait pattern in children with CP and, in particular, the evaluation of push-off ability before and after treatment. Twenty children with CP were evaluated by clinical examination and three-dimensional gait analysis (GA) before and after (12 months) gastrocnemius fascia lengthening surgery (modified Vulpius' technique) to improve equinus foot and walking. The results showed a significant reduction in equinus foot, represented by a re-duction in the â angle (the angle between the foot and the ground on the sagittal plane) at initial contact (IC), closer to healthy children, and increased ankle power generation during push-off. Even if this result was not of a statistically significant level, it is important because it means that the surgery did not produce a functional weakness. Kinetic results showed an improvement (ankle joint power absorbed and generated) related to a more functional walking behavior. Some improvements concerning the knee joint are significant, in particular, the value of the knee angle at IC and of peak during the swing phase.


When is adult hippocampal neurogenesis necessary for learning? evidence from animal research.
The hippocampus is a key brain structure involved in the short- and long-term processing of declarative memory. Since adult hippocampal neurogenesis was first found, numerous studies have tried to establish the contribution of newborn neurons to hippocampus-dependent cognitive functions. However, this large amount of research has generated contradictory results. In this paper, we review the body of evidence investigating the relationship between hippocampal neurogenesis and learning to conclude the functional role of adult-born hippocampal neurons. First, factors that could explain discrepancies among experiments are taken into account. Then, in addition to methodological differences, we emphasize the importance of the age of the newborn neurons studied, as to how their maturation influences both their properties and potential functionality. Next, we discuss which declarative memory components could require involvement of adult hippocampal neurogenesis, taking into consideration the representational demands of the task, its difficulty and the level of performance reached by the subject. Finally, other factors that could modulate neurogenesis and memory, such as stress levels or previous experience of the animal, should also be taken into consideration in interpreting experiments focused on neurogenesis. In conclusion, our analysis of published studies suggests that new adult-born neurons, under certain circumstances, have a crucial and irreplaceable role in hippocampal learning.


Evaluation of a labor and delivery videodisc simulation.
The purpose of this project was to determine the impact of an interactive videodisc (IVD) simulation in labor and delivery on the learning and clinical confidence of junior-level nursing students. Two clinical groups of students were created from the total 39 and both groups were pretested on knowledge and clinical confidence. Group 1 (n = 18) completed the IVD program before the first clinical experience in the labor and delivery setting. Group 2 (n = 21) received a traditional clinical experience first and then completed the IVD program. Students completing the IVD program plus the clinical experience had significantly greater clinical confidence and learning than those students completing only the clinical experience. Evaluation comments provided suggestions for improvements and were filled with positive comments about the program.


Recent contributions to the field of subjective cognitive decline in aging: A literature review.
Subjective cognitive decline (SCD) is defined as self-experienced, persistent concerns of decline in cognitive capacity in the context of normal performance on objective cognitive measures. Although SCD was initially thought to represent the "worried well," these concerns can be linked to subtle brain changes prior to changes in objective cognitive performance and, therefore, in some individuals, SCD may represent the early stages of an underlying neurodegenerative disease process (e.g., Alzheimer's disease). The field of SCD research has expanded rapidly over the years, and this review aims to provide an update on new advances in, and contributions to, the field of SCD in key areas and themes identified by researchers in this field as particularly important and impactful. First, we highlight recent studies examining sociodemographic and genetic risk factors for SCD, including explorations of SCD across racial and ethnic minoritized groups, and examinations of sex and gender considerations. Next, we review new findings on relationships between SCD and in vivo markers of pathophysiology, utilizing neuroimaging and biofluid data, as well as associations between SCD and objective cognitive tests and neuropsychiatric measures. Finally, we summarize recent work on interventions for SCD and areas of future growth in the field of SCD.


Splicing alterations in healthy aging and disease.
Alternative RNA splicing is a key step in gene expression that allows generation of numerous messenger RNA transcripts encoding proteins of varied functions from the same gene. It is thus a rich source of proteomic and functional diversity. Alterations in alternative RNA splicing are observed both during healthy aging and in a number of human diseases, several of which display premature aging phenotypes or increased incidence with age. Age-associated splicing alterations include differential splicing of genes associated with hallmarks of aging, as well as changes in the levels of core spliceosomal genes and regulatory splicing factors. Here, we review the current known links between alternative RNA splicing, its regulators, healthy biological aging, and diseases associated with aging or aging-like phenotypes. This article is categorized under: RNA in Disease and Development > RNA in Disease RNA Processing > Splicing Regulation/Alternative Splicing.


Expanding the toolbox for Trypanosoma cruzi: A parasite line incorporating a bioluminescence-fluorescence dual reporter and streamlined CRISPR/Cas9 functionality for rapid in vivo localisation and phenotyping.
Infection with Trypanosoma cruzi causes Chagas disease, a major public health problem throughout Latin America. There is no vaccine and the only drugs have severe side effects. Efforts to generate new therapies are hampered by limitations in our understanding of parasite biology and disease pathogenesis. Studies are compromised by the complexity of the disease, the long-term nature of the infection, and the fact that parasites are barely detectable during the chronic stage. In addition, functional dissection of T. cruzi biology has been restricted by the limited flexibility of the genetic manipulation technology applicable to this parasite. Here, we describe two technical innovations, which will allow the role of the parasite in disease progression to be better assessed. First, we generated a T. cruzi reporter strain that expresses a fusion protein comprising red-shifted luciferase and green fluorescent protein domains. Bioluminescence allows the kinetics of infection to be followed within a single animal, and specific foci of infection to be pinpointed in excised tissues. Fluorescence can then be used to visualise individual parasites in tissue sections to study host-parasite interactions at a cellular level. Using this strategy, we have been routinely able to find individual parasites within chronically infected murine tissues for the first time. The second advance is the incorporation of a streamlined CRISPR/Cas9 functionality into this reporter strain that can facilitate genome editing using a PCR-based approach that does not require DNA cloning. This system allows the rapid generation of null mutants and fluorescently tagged parasites in a background where the in vivo phenotype can be rapidly assessed. The techniques described here will have multiple applications for studying aspects of T. cruzi biology and Chagas disease pathogenesis previously inaccessible to conventional approaches. The reagents and cell lines have been generated as a community resource and are freely available on request.


Placebo found equivalent to amoxicillin for treatment of acute bronchitis in Nairobi, Kenya: a triple blind, randomised, equivalence trial.
Antibiotic treatment is not recommended for acute bronchitis in immunocompetent patients in industrialised countries. Whether these recommendations are relevant to the developing world and to immunocompromised patients is unknown. Randomised, triple blind, placebo controlled equivalence trial of amoxicillin compared with placebo in 660 adults presenting to two outpatient clinics in Nairobi, Kenya, with acute bronchitis but without evidence of chronic lung disease. The primary study end point was clinical cure, as defined by a >or=75% reduction in a validated Acute Bronchitis Severity Score by 14 days; analysis was by intention to treat with equivalence defined as <or=8% difference between study arms. Clinical cure rates in the amoxicillin and placebo arms were 81.7% and 84.0%, respectively (difference 2.3%, 95% CI -8.6% to 4.0%). Of 131 HIV infected subjects (19.8%), cure rates for those randomised to amoxicillin (77.2%) and placebo (83.8%) differed by 6.6% (95% CI -21.7% to 8.6%). Among HIV uninfected subjects, the difference in cure rates was 1.6% (95% CI -8.5% to 5.3%). Potential drug side effects were similar in the two arms. No subjects required hospitalisation or died. Antibiotic treatment of acute bronchitis is unhelpful, even in populations with a high prevalence of HIV infection.


Physical fitness, academic achievement, and socioeconomic status in school-aged youth.
This study examined the association between physical fitness and academic achievement and determined the influence of socioeconomic status (SES) on the association between fitness and academic achievement in school-aged youth. Overall, 1,701 third-, sixth-, and ninth-grade students from 5 school districts participated in the assessments. Fitness was assessed using FITNESSGRAM (aerobic fitness, muscular strength, muscular endurance, flexibility, and body composition). Results were used to determine individual fitness scores. Academic achievement was measured by standardized tests for Math (all grades), English (all grades), and Social Studies (sixth and ninth grades only). The SES was determined using eligibility for free and reduced lunch program. There were no significant differences between fitness groups for Math and English in third-grade students. Sixth- and ninth-grade students with high fitness scored significantly better on Math and Social Studies tests compared with less fit students. Lower SES students scored significantly worse on all tests. Muscular strength and muscular endurance were significantly associated with academic achievement in all grades. Compared with all other variables, SES appears to have the strongest association with academic achievement. However, it also appears that high fitness levels are positively associated with academic achievement in school-aged youth.


[Effectiveness of combined administration of lithium carbonate and prednisolone in neutropenias].
Use was made of 3 schedules of the combined use of lithium carbonate and prednisolone in patients with neutropenias of different genesis. Prednisolone was used in a single dose on day 10 of lithium carbonate intake (1), prednisolone was included into lithium carbonate therapy (2), and lithium carbonate was included into prednisolone therapy (3). The effect attained with the combined use of prednisolone and lithium carbonate appeared higher as compared to that with the use of each drug alone. The data obtained point to the differences between lithium carbonate and prednisolone if viewed from the standpoint of the mechanism of the neutropoiesis-stimulating action. It is recommended that lithium carbonate (0.3 g thrice a day) may be combined with prednisolone (0.4 mg/kg bw a day). The latter drug should be included into the treatment schedule since the 4th day of lithium therapy for neutropenias of different genesis including those caused by cytostatic treatment and irradiation.


Increased gastric epithelial cell apoptosis associated with colonization with cagA + Helicobacter pylori strains.
Gastric colonization by Helicobacter pylori is a risk factor for noncardia gastric cancer. The association between H. pylori and cancer may be attributable to increased epithelial cell turnover, possibly related to antigastric antibodies. Two previous studies reported a disproportionate increase in proliferation relative to apoptosis in patients with H. pylori strains expressing the virulence-related cagA gene. This has led to the hypothesis that an abrogation of apoptosis by cagA-positive strains may promote neoplasia. We, therefore, examined the effect of H. pylori on gastric epithelial proliferation, apoptosis, and the presence of serum antiparietal cell antibodies in a large prospective study. Proliferation and apoptosis were evaluated "blindly" using validated immunohistochemical methods in two antral and two gastric corpus biopsies from 60 patients with nonulcer dyspepsia, and results were correlated with the presence of serum antiparietal cell antibodies. H. pylori colonization was assessed by histology, biopsy urease test, and serology. Proliferation was increased 2-fold in both antrum and corpus in H. pylori-positive patients, was not related to H. pylori cagA status, and was positively correlated with histological gastritis. Apoptosis was increased in the antrum and body only in patients with cagA-positive H. pylori strains. Antiparietal cell antibodies were not more prevalent in H. pylori colonization, and their presence was inversely related to epithelial apoptosis scores we therefore conclude that in patients with nonulcer dyspepsia, H. pylori carriage is associated with increased proliferation. Futhermore the cag pathogenicity island is associated with increased apoptosis. Our results do not support the hypothesis that there is a relative deficiency of gastric epithelial cell apoptosis associated with the carriage of cagA-positive strains. Host factors may be more important than bacterial products in determining the long-term outcome of H. pylori colonization.


Diverse pathways for salicin utilization in Shigella sonnei and Escherichia coli carrying an impaired bgl operon.
Utilization of the aryl-β-glucosides salicin or arbutin in most wild-type strains of E. coli is achieved by a single-step mutational activation of the bgl operon. Shigella sonnei, a branch of the diverse E. coli strain tree, requires two sequential mutational steps for achieving salicin utilization as the bglB gene, encoding the phospho-β-glucosidase B, harbors an inactivating insertion. We show that in a natural isolate of S. sonnei, transcriptional activation of the gene SSO1595, encoding a phospho-β-glucosidase, enables salicin utilization with the permease function being provided by the activated bgl operon. SSO1595 is absent in most commensal strains of E. coli, but is present in extra-intestinal pathogens as bgcA, a component of the bgc operon that enables β-glucoside utilization at low temperature. Salicin utilization in an E. coli bglB laboratory strain also requires a two-step activation process leading to expression of BglF, the PTS-associated permease encoded by the bgl operon and AscB, the phospho-β-glucosidase B encoded by the silent asc operon. BglF function is needed since AscF is unable to transport β-glucosides as it lacks the IIA domain involved in phopho-relay. Activation of the asc operon in the Sal(+) mutant is by a promoter-up mutation and the activated operon is subject to induction. The pathway to achieve salicin utilization is therefore diverse in these two evolutionarily related organisms; however, both show cooperation between two silent genetic systems to achieve a new metabolic capability under selection.


Isolation and characterization of soybean-associated bacteria and their potential for plant growth promotion.
Endophytic and epiphytic bacteria were isolated from two soybean cultivars (Foscarin and Cristalina). Significant differences were observed in bacterial population densities in relation to season of isolation, soybean growth phase and the tissues from which the isolates were obtained. The isolates were identified by partial 16S rDNA sequence analysis, with most of the isolates belonging to the Pseudomonaceae, Burkholderiacea and Enterobacteriaceae groups. The potential of the isolates for plant growth promotion was evaluated by screening for indoleacetic acid (IAA) production and mineral phosphate solubilization; 34% of endophytic bacteria produced IAA and 49% were able to solubilize mineral phosphate whereas only 21% of epiphytic bacteria produced IAA although 52% were able to solubilize mineral phosphate. A high frequency of IAA producing isolates occurred in the early ripening Foscarin cultivar whereas a high percentage of phosphate solubilizing isolates were obtained from plants in the initial development stage (V6). We also found that 60% of endophytic and 69% of epiphytic isolates that produced IAA and solubilized mineral phosphate were also able to fix nitrogen in vitro. The soybean-associated bacteria showing characteristics related to plant growth promotion were identified as belonging to the genera Pseudomonas, Ralstonia, Enterobacter, Pantoea and Acinetobacter.


Iron-binding fragments from the carboxyl-terminal region of hen ovotransferrin.
1. When iron-saturated hen ovotransferrin was treated with subtilisin the N-terminal half was digested at a faster rate than the C-terminal half, allowing the latter to be isolated as a single-chain fragment of mol.wt 35000. 2. In mildly acid conditions iron-ovotransferrin loses iron preferentially from its N-terminal binding site. Trypsin digestion of the resulting monoferric ovotransferrin also gave rise to a C-terminal fragment. 3. Comparison of the N-terminal fragment with the C-terminal fragments shows differences in composition, peptide 'maps', CNBr-cleavage patterns and antigenic structures. The C-terminal fragments carry the carbohydrate group of ovotransferrin. 4. Both N-terminal and C-terminal fragments donate their bound iron to rabbit reticulocytes.


Lymphoid tissue- and inflammation-specific endothelial cell differentiation defined by monoclonal antibodies.
Endothelial cells play an essential role in immune responses by regulating the entry of leukocytes into lymphoid tissues and sites of inflammation. As an initial approach to analyzing endothelial cell specialization in relation to such immune function, we have produced monoclonal antibodies (MAB) against mouse lymph node endothelium. Three antibodies were selected: MECA-20, recognizing the endothelium of all blood vessels in lymphoid as well as non-lymphoid organs; MECA-217, which stains the endothelium lining large elastic arteries, but among small vessels is specific for post-capillary venules within lymphoid organs and tissues exposed to exogenous antigen, such as skin and uterus; and MECA-325, an antibody that demonstrates specificity for the specialized high endothelial venules (HEV) that control lymphocyte homing into lymph nodes and Peyer's patches. MECA-325 failed to stain vessels in any non-lymphoid organs tested. Immunoperoxidase studies of HEV in lymph node frozen sections, and of isolated high endothelial cells in suspensions, demonstrated that the antigens recognized by all three antibodies are expressed at the cell surface; those defined by MECA-20 and MECA-325 are also present in the cytoplasm. To study the regulation of the antigens defined by these MAB in relation to extra-lymphoid immune reactions, we assessed their expression in induced s.c. granulomas as a model for chronic inflammation. Small vessels in the granulomas were already stained by MECA-217 in the first days of development. In contrast MECA-325 detected postcapillary venules (which frequently displayed the morphologic characteristics of HEV) only from approximately 1 wk, in parallel with the development of a persistent mononuclear cell infiltrate including numerous lymphocytes. The selective appearance of the MECA-325 antigen on vascular endothelium supporting lymphocyte traffic in both lymphoid and extra-lymphoid sites suggests that this antigen may play an important role in the process of lymphocyte extravasation. The demonstration of lymphoid organ- and inflammation-specific microvascular antigens offers direct evidence for a complex specialization of endothelium in relation to immune stimuli, and supports the concept that microvascular differentiation may play an important role in local immune responses.


Ocular effects of hyoscine in double dose transdermal administration and its reversal by low dose pyridostigmine.
The potential of low dose (30 mg t.i.d) pyridostigmine to reduce the ocular side effects of double dose transdermal controlled release hyoscine was evaluated by the study of near visual acuity, accommodation amplitude and pupil diameter in a placebo controlled, double masked study. We studied 47 healthy men (age 18-21 yr) in 3 groups: 16 assigned to placebo hyoscine and placebo pyridostigmine, 15 assigned to double dose hyoscine and placebo pyridostigmine, and 16 to double dose hyoscine and pyridostigmine. Subjects were tested during 48 h of treatment and 48 h of washout period. Blood cholinesterase inhibition level and amount of hyoscine released from the patches were used as parameters of reliability. Difference between groups was assessed using change from baseline scores. Double dose hyoscine caused decrease in near visual acuity to a mean of 14/18. Accommodation amplitude was decreased in the double dose transdermal hyoscine group from 9.19 +/- 1.04 to 4.83 +/- 1.97 diopters of accommodation. This decrease was significant when compared to the placebo group (p < 0.05) and to the pyridostigmine-protected group (p < 0.05). Pyridostigmine, however, did not significantly change the hyoscine-induced mydriasis of 1.47 + 0.15 mm change from baseline (p < 0.05). These results suggest that pyridostigmine administration may be beneficial in shortening recovery time when near vision impairment is experienced following single and double dose transdermal hyoscine administration.


Inverse methods for design of soft materials.
Functional soft materials, comprising colloidal and molecular building blocks that self-organize into complex structures as a result of their tunable interactions, enable a wide array of technological applications. Inverse methods provide a systematic means for navigating their inherently high-dimensional design spaces to create materials with targeted properties. While multiple physically motivated inverse strategies have been successfully implemented in silico, their translation to guiding experimental materials discovery has thus far been limited to a handful of proof-of-concept studies. In this perspective, we discuss recent advances in inverse methods for design of soft materials that address two challenges: (1) methodological limitations that prevent such approaches from satisfying design constraints and (2) computational challenges that limit the size and complexity of systems that can be addressed. Strategies that leverage machine learning have proven particularly effective, including methods to discover order parameters that characterize complex structural motifs and schemes to efficiently compute macroscopic properties from the underlying structure. We also highlight promising opportunities to improve the experimental realizability of materials designed computationally, including discovery of materials with functionality at multiple thermodynamic states, design of externally directed assembly protocols that are simple to implement in experiments, and strategies to improve the accuracy and computational efficiency of experimentally relevant models.


Investigation of the threshold for allergic reactivity to chromium.
Allergy to chromium is relatively common, often in association with exposure to cement or in leather manufacture. However, in certain locations, there appears to be a relatively large cohort of chromium-sensitive individuals whose allergy cannot be explained by these common sources. In particular, this group include Israeli housewives with persistent hand eczema and concomitant patch test positivity to chromium. The causation of their allergy has been linked with relatively high levels of chromium contamination in household products. To provide further information in respect of the definition of safe levels for such products, we examined 17 chromium-allergic individuals to determine their threshold for reaction under closed patch test and repeated open application test (ROAT) conditions. The data derived indicated that, on normal skin, the patch test threshold was 10 ppm chromium; in the presence of an irritant (sodium lauryl sulfate) the threshold was closer to 1 ppm, 2/17 subjects giving 1+ reactions at this concentration. In the more realistic exposure conditions of the ROAT, 8/14 individuals failed to react to 50 ppm, whilst 3/15 reacted to 5 ppm. Interestingly, there was very poor correlation between patch test sensitivity and ROAT sensitivity. To ensure the large majority of chromium-allergic individuals do not suffer elicitation of their allergy, as well as to limit the development of new chromium-sensitive subjects, it is recommended that household products adhere to a previously published standard of a maximum limit of 5 ppm, with an ultimate target of 1 ppm contamination by chromium.


Quality of care in humanitarian surgery.
Humanitarian surgical programs are set up de novo, within days or hours in emergency or disaster settings. In such circumstances, insuring quality of care is extremely challenging. Basic structural inputs such as a safe structure, electricity, clean water, a blood bank, sterilization equipment, a post-anesthesia recovery unit, appropriate medications should be established. Currently, no specific credentials are needed for surgeons to operate in a humanitarian setting; the training of more humanitarian surgeons is desperately needed. Standard perioperative protocols for the humanitarian setting after common procedures such as Cesarean section, burn care, open fractures, and amputations and antibiotic prophylaxis, and post-operative pain management must be developed. Outcome data, especially long-term outcomes, are difficult to collect as patients often do not return for follow-up and may be difficult to trace; standard databases for post-operative infections and mortality rates should be established. Checklists have recently received significant attention as an instrument to support the improvement of surgical quality; knowing which items are most applicable to humanitarian settings remains unknown. In conclusion, the quality of surgical services in humanitarian settings must be regulated. Many other core medical activities of humanitarian organizations such as therapeutic feeding, mass vaccination, and the treatment of infectious diseases, such as tuberculosis and human immunodeficiency virus, are subject to rigorous reporting of quality indicators. There is no reason why surgery should be exempted from quality oversight. The surgical humanitarian community should pull together before the next disaster strikes.


Matrix metalloproteinases 2 and 9 in situ mRNA expression in colorectal tumors from Iraqi patients.
Matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) preferentially degrade the basement membrane, a key step in tumor invasion, metastases, and induction of vascularization of tumor tissue. To determine MMP-2 and MMP-9 in situ mRNA expressions in colorectal adenocarcinomas from Iraqi patients. Forty archived paraffin-embedded colorectal adenocarcinoma samples and their resection margins were enrolled in our study. Thin paraffin embedded sections (3-5 μm thick) of both tumor and resection margins were prepared for each respective biopsy and were used to detect MMP-2 and MMP-9 in situ mRNA expressions based on in situ hybridization technique. Statistical analyses were conducted to describe different variables and parameters in this research, and to describe relationships with each other as well. For the comparisons, the t test of significance was used. The associations were found by chi-square (χ2 ) and analysis of variance (ANOVA) tests, or as appropriate, as well as 95% confidence interval. The correlations were calculated using correlation coefficient (r). Statistical significance was defined as P < 0.05. Based on the current outcome, there were significant differences in MMP-2 and MMP-9 in situ mRNA expressions when each tumor sample were compared to its respective resection margin (P < 0.001 and P < 0.001, respectively). When tumor samples were analyzed based on their depth of invasion, means of in situ mRNA expressions of both MMP-2 and MMP-9 were significantly increased in the group in which tumor invaded submucosa into muscularis properia (SMP) compared to that of tumor in serosa (SE) group and tumor invading other organs (OR) group (P < 0.05 and P < 0.05, respectively). Furthermore, when tumor lymph node metastases were questioned, exclusively, MMP-2 in situ mRNA expression was significantly differentiated among N0, N1, and N2 groups (P < 0.05). Regarding the possible correlation between the two investigated parameters with respect to various histopathological variables, both MMP-2 and MMP-9 in situ mRNA expressions have significant positive correlation in tumor samples (r = 0.88), whereas in resection margins, this correlation was absent. Interestingly, MMP-2 and MMP-9 in situ mRNA expressions were found to correlate positively as well as significantly within tumor differentiation [well-differentiated (WD) adenocarcinoma: r = 0.78; moderately differentiated (MD) adenocarcinoma: r = 0.90; and poorly differentiated (PD) adenocarcinoma: r = 0.91], tumor stage (A-B: r = 0.70 and C-D: r = 0.95), depth of invasion (SMP: r = 0.77; SE: r = 0.87; and OR: r = 0.97), lymph node metastasis (N0: r = 0.82; N1: r = 0.92; and N2: r = 0.96), and tumor size (<3 mm 3 : r = 0.76 versus ≥3 mm3: r = 0.94). Overexpression of MMP-2 and MMP-9 are often associated with increased invasive metastatic potential of colorectal adenocarcinoma. However, their activities are essential during the early stages of tumor progression.


Cognitive Interviews of Vietnamese Americans on Healthy Eating and Physical Activity Health Educational Materials.
The purpose of this study was to better understand if a health educational presentation using culturally adapted materials was understandable and culturally appropriate, and that the content was retained, in an older Vietnamese American population. This study used cognitive interviewing. A convenient sampling was used to recruit eight participants by staff of a community-based organization from its client base. This is the first study to document that family eating style poses a challenge for estimating food intake among Vietnamese Americans. Participants who ate in a family eating style were not able to recall or estimate the number of servings of protein and vegetables. Some older Vietnamese Americans used food for healing and self-adjusted portion sizes from dietary recommendations. Cognitive interviewing is a useful method to improve comprehension, retention, and cultural appropriateness of health educational materials. Further nutrition research concerning intake measurement in ethnic groups that practice a family eating style is warranted.


Coexpressed Class B G Protein-Coupled Secretin and GLP-1 Receptors Self- and Cross-Associate: Impact on Pancreatic Islets.
Class B guanine nucleotide-binding protein (G protein)-coupled receptors form symmetrical homodimeric complexes along the lipid face of transmembrane segment 4 (TM4) and can form heterodimeric complexes, although their structure is unknown. The current study demonstrates that the lipid face of TM4 is also the predominant determinant for formation of heteroreceptor complexes between two class B receptors, secretin receptor (SecR) and glucagonlike peptide-1 receptor (GLP-1R), which are expressed on pancreatic islet cells. Because these receptors use the same interface for formation of homo- and heteroreceptor complexes, competitive forces may affect expression of different complexes. Assessment of SecR and GLP-1R dimeric complexes via recombinant expression in Chinese hamster ovary cells revealed that homodimeric receptor complexes were more stable than the heterodimeric complexes, and the homodimeric SecR/SecR is more stable than the GLP-1R/GLP-1R complex. Given the greater tendency for homodimeric compared with heterodimeric complex formation, the heteroreceptor complexes lacked the expression that might have been predicted by geometry alone. Nevertheless, cells coexpressing these receptors formed heterodimeric complexes that correlated with reduced intracellular calcium responses to secretin, but no change in the cyclic adenosine monophosphate responses to each natural agonist. This functional effect was confirmed in pancreatic islets isolated from wild-type and GLP-1R knockout mice. In these cells, the increased calcium response mediated by secretin in the absence of GLP-1R was paralleled by an increased glucose-dependent insulin response, indicating that the heterodimeric receptor complexes modulate secretin responses. Furthermore, the heterodimeric receptor complexes also mediated agonist-induced cross-receptor internalization, a process that could have broad functional significance in sites of natural receptor coexpression.


Adding effect sizes to a systematic review on interventions for promoting physical activity among European teenagers.
This commentary adds effect sizes to the recently published systematic review by De Meester and colleagues and provides a more detailed insight into the effectiveness of interventions to promote physical activity among European teenagers. The main findings based on this evidence were: (1) school-based interventions generally lead to short term improvement in physical activity levels, but there were large differences between interventions with regard to effect sizes; (2) a multi-component approach (including environmental components) generally resulted in larger effect sizes, thereby providing evidence for the assumption that a multi-component approach should produce synergistic results; and (3) if an intervention aimed to affect more health behaviours besides physical activity, then the intervention appeared to be less effective in favour of physical activity.


Biana: a software framework for compiling biological interactions and analyzing networks.
The analysis and usage of biological data is hindered by the spread of information across multiple repositories and the difficulties posed by different nomenclature systems and storage formats. In particular, there is an important need for data unification in the study and use of protein-protein interactions. Without good integration strategies, it is difficult to analyze the whole set of available data and its properties. We introduce BIANA (Biologic Interactions and Network Analysis), a tool for biological information integration and network management. BIANA is a Python framework designed to achieve two major goals: i) the integration of multiple sources of biological information, including biological entities and their relationships, and ii) the management of biological information as a network where entities are nodes and relationships are edges. Moreover, BIANA uses properties of proteins and genes to infer latent biomolecular relationships by transferring edges to entities sharing similar properties. BIANA is also provided as a plugin for Cytoscape, which allows users to visualize and interactively manage the data. A web interface to BIANA providing basic functionalities is also available. The software can be downloaded under GNU GPL license from http://sbi.imim.es/web/BIANA.php. BIANA's approach to data unification solves many of the nomenclature issues common to systems dealing with biological data. BIANA can easily be extended to handle new specific data repositories and new specific data types. The unification protocol allows BIANA to be a flexible tool suitable for different user requirements: non-expert users can use a suggested unification protocol while expert users can define their own specific unification rules.


Confounding factors and genetic polymorphism in the evaluation of individual steroid profiling.
In the fight against doping, steroid profiling is a powerful tool to detect drug misuse with endogenous anabolic androgenic steroids. To establish sensitive and reliable models, the factors influencing profiling should be recognised. We performed an extensive literature review of the multiple factors that could influence the quantitative levels and ratios of endogenous steroids in urine matrix. For a comprehensive and scientific evaluation of the urinary steroid profile, it is necessary to define the target analytes as well as testosterone metabolism. The two main confounding factors, that is, endogenous and exogenous factors, are detailed to show the complex process of quantifying the steroid profile within WADA-accredited laboratories. Technical aspects are also discussed as they could have a significant impact on the steroid profile, and thus the steroid module of the athlete biological passport (ABP). The different factors impacting the major components of the steroid profile must be understood to ensure scientifically sound interpretation through the Bayesian model of the ABP. Not only should the statistical data be considered but also the experts in the field must be consulted for successful implementation of the steroidal module.


Tunable Tesla-Scale Magnetic Attosecond Pulses through Ring-Current Gating.
Coherent control over electron dynamics in atoms and molecules using high-intensity circularly polarized laser pulses gives rise to current loops, resulting in the emission of magnetic fields. We propose, and demonstrate with ab initio calculations, "current-gating" schemes to generate direct or alternating-current magnetic pulses in the infrared spectral region, with highly tunable waveform and frequency, and showing femtosecond-to-attosecond pulse duration. In optimal conditions, the magnetic pulse can be highly isolated from the driving laser and exhibits a high flux density (∼1 T at a few hundred nanometers from the source, with a pulse duration of 787 attoseconds) for application in forefront experiments of ultrafast spectroscopy. Our work paves the way toward the generation of attosecond magnetic fields to probe ultrafast magnetization, chiral responses, and spin dynamics.


The 3-minute all-out cycling test is sensitive to changes in cadence using the Lode Excalibur Sport ergometer.
This study investigated the effect cadence has on the estimation of critical power (CP) and the finite work capacity (W') during the 3-minute all-out cycling test. Ten participants completed 8 tests: 1) an incremental test to calculate gas exchange threshold (GET), maximal aerobic power (MAP) and peak oxygen uptake (V̇O2peak), 2-4) three time-to-exhaustion tests at 80, 100 and 105% MAP to calculate CP and W', 5-7) four 3-minute all-out tests to calculate end power (EP) and work done above EP (WEP) using cadences ranging from preferred -5 to preferred +10 rev·min-1 to set the fixed resistance. Significant differences were seen between CP and EP-preferred (267.5 ± 22.6 W vs. 296.6 ± 26.1 W, P < 0.001), CP and EP-5 (267.5 ± 22.6 W vs. 303.6 ± 24.0 W, P < 0.001) and between CP and EP+5 (267.5 ± 22.6 W vs. 290.0 ± 28.0 W, P = 0.002). No significant differences were seen between CP and EP+10 (267.5 ± 22.6 W vs. 278.1 ± 30.9 W, P = 0.331). Significant differences were seen between W' and WEP at all tested fixed resistances. EP is reduced when cycling at higher than preferred cadences, providing better estimates of CP.


Effects of weight changes produced by exercise, food restriction, or overeating on body composition.
The body weight of rats was reduced by exercise or by restriction of food intake over a period of 18 wk. Body composition was studied to determine if exercise protects against the loss of lean tissue that can occur as a result of a negative caloric balance. Rats weighing 706 +/-14 g were divided into four groups matched for weight. A baseline group was killed at the beginning of the study. An exercising group, fed ad lib., was subjected to a program of swimming. A sedentary, free-eating group was provided with food ad lib. Two sedentary, paired-weight subgroups were calorie restricted so that they lost weight at the same rate as the exercisers. The protein intake of one paired-weight subgroup was matched with that of the exercising group. The other sedentary, paired-weight animals ate the standard diet. There was no significant difference in body composition between the two sedentary, paired-weight subgroups which were, therefore, pooled for comparison with the other groups. The exercisers lost 182+/-19 g as a result of both an increase in caloric expenditure and a decrease in appetite. The sedentary, food-restricted animals lost an average of 182+/-18 g. The sedentary, free-eating animals gained 118+/-13 g. The carcasses of the exercised animals contained significantly less fat and more lean tissue than those of the sedentary, paired-weight animals, providing evidence for a fat mobilizing and protein conserving effect of exercise. The composition of the body substance lost by the exercising animals was 78% fat, 5% protein, 1% minerals, and 16% water, compared to 62% fat, 11% protein, 1% minerals, and 26% water for the sedentary, food-restricted rats. Fat accounted for 87% and water for 10% of the weight gained by the sedentary, free-eating animals.


Comparison of head impact exposure in practice drills among multiple youth football teams.
Limiting contact in football practice can reduce the number of head impacts a player receives, but further research is needed to inform the modification of optimal drills that mitigate head impact exposure (HIE) while the player develops the skills needed to safely play the game. This study aimed to compare HIE in practice drills among 6 youth football teams and to evaluate the effect of a team on HIE. On-field head impact data were collected from athletes (ages 10–13 years) playing on 6 local youth football teams (teams A–F) during all practices using the Head Impact Telemetry System. Video was recorded and analyzed to verify and assign impacts to a specific drill. Drills were identified as follows: dummy/sled tackling, half install, install, install walk through, multiplayer tackle, Oklahoma, one-on-one, open field tackling, other, passing, position skill work, scrimmage, special teams, tackling drill stations, and technique. HIE was quantified in terms of impacts per player per minute (ppm) and peak linear and rotational head acceleration. Generalized linear models were used to assess differences in head impact magnitude and frequency among drills as well as among teams within the most common drills. Among 67 athlete-seasons, a total of 14,718 impacts during contact practices were collected and evaluated in this study. Among all 6 teams, the mean linear (p < 0.0001) and rotational (p < 0.0001) acceleration varied significantly among all drills. Open field tackling had significantly (p < 0.001) higher mean linear acceleration than all other drills. Multiplayer tackle had the highest mean impact rate (0.35 ppm). Significant variations in linear acceleration and impact rate were observed among teams within specific drills. Team A had the highest mean linear acceleration in install, one-on-one, and open field tackling and the highest mean impact rate in Oklahoma and position skill work. Although team A spent the greatest proportion of their practice on minimal- or no-player versus player contact drills (27%) compared to other teams, they had the highest median (20.2g) and 95th percentile (56.4g) linear acceleration in practice. Full-speed tackling and blocking drills resulted in the highest HIE. Reducing time spent on contact drills relative to minimal or no contact drills may not lower overall HIE. Instead, interventions such as reducing the speed of players engaged in contact, correcting tackling technique, and progressing to contact may reduce HIE more effectively.


A novel statistical model for mandibular helical axis analysis.
The purpose of this study was to establish a new statistical method for the analysis of noisy mandibular helical axis parameters, especially the position vector of the finite helical axis (FHA). The subjects were children with anterior cross-bite who had received orthodontic treatment. Maximum mouth-opening was measured by means of an opto-electronic motion analysis system. These movements were compared with similar movement in the same group after treatment of their anterior cross-bite. Each curve of FHA position vectors was modelled as a spline function with random coefficients. To determine the optimal number of knots, two criteria were used: deviance information criteria (DIC) and mean squared prediction error (MSE). We were interested in estimating a typical curve for a population. Self-modelling regression (SEMOR) was extended to three dimensions to model groups of three-dimensional curves. Each curve was modelled as a spline function using nine knots. Population average curves were created using SEMOR. This study provided detailed information about jaw movement for comparing cross-bite to normal occlusion by calculating the population mean curves of the position vector of the FHA. Our results suggested that the two population mean curves for the position vector of the FHA were significantly different in the closing phase. The combination of a spline function with random coefficients and SEMOR extended to three dimensions can be used not only for FHA analysis but also for the analysis of other jaw movements.


Digestion of bamboo compared to grass and lucerne in a small hindgut fermenting herbivore, the guinea pig (Cavia porcellus).
Bamboo is an enigmatic forage, representing a niche food for pandas and bamboo lemurs. Bamboo might not represent a suitable forage for herbivores relying on fermentative digestion, potentially due to its low fermentability. To test this hypothesis, guinea pigs (n = 36) were used as model species and fed ad libitum with one of three forages (bamboo, lucerne, or timothy grass) in a fresh or dried state, with six individuals per group, for 3 weeks. The nutrient composition and in vitro fermentation profile of bamboo displayed low fermentation potential, i.e. high lignin and silica levels together with a gas production (Hohenheim gas test) at 12 h of only 36% of that of lucerne and grass. Although silica levels were more abundant in the leftovers of (almost) all groups, guinea pigs did not select against lignin on bamboo. Dry matter (DM) intake was highest and DM digestibility lowest on the bamboo forage. Total short-chain fatty acid levels in caecal content were highest for lucerne and lowest for grass and bamboo. Bamboo-fed guinea pigs had a lower body weight gain than the grass and lucerne group. The forage hydration state did not substantially affect digestion, but dry forage led to a numerically higher total wet gut fill. Although guinea pigs increased DM intake on the bamboo diet, the negative effects on fermentation of lignin and silica in bamboo seemed overriding. For herbivores that did not evolutionary adapt, bamboo as an exclusive food resource can be considered as inadequate.


Effective synthesis of kynurenine-containing peptides via on-resin ozonolysis of tryptophan residues: synthesis of cyclomontanin B.
The preparation of Kyn-containing peptides is difficult, owing to the low reactivity of Kyn in the coupling reaction. In this report, Kyn-containing peptides were efficiently obtained via on-resin ozonolysis of the corresponding Trp-containing peptide. In addition, a Kyn-containing cyclic peptide, cyclomontanin B, has been synthesized by this strategy in the combination with serine/threonine ligation (STL)-mediated cyclization.


Biological monitoring of low-dose interleukin 2 in humans: soluble interleukin 2 receptors, cytokines, and cell surface phenotypes.
Different immunotherapy regimens using s.c. recombinant interleukin-2 (rIL-2) were studied in 76 patients with progressive metastatic renal carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, or Hodgkin's disease. To assess the immunomodulatory capacity of rIL-2, we measured serum levels of soluble interleukin-2 (sIL-2) receptors, gamma-interferon, tumor necrosis factor-alpha, and various lymphocyte subsets expressing the CD25 Tac IL-2 receptor and the CD56 natural killer (NK) associated antigen. Additionally, we measured serum antibodies specific to rIL-2 in order to evaluate immunogenicity of rIL-2. In all patients, a significant increase in sIL-2 receptor levels could be observed when comparing values on day 0 and after one treatment course. Patients developing a neutralizing anti-rIL-2 antibody exhibited significantly lower serum sIL-2 receptor levels than patients without antibody. Soluble IL-2 receptors correlated with the percentage of CD25 IL-2 receptor-positive peripheral blood lymphocytes. Both soluble and cell surface IL-2 receptors exhibited a significant increase during rIL-2 therapy but did not correlate with the percentage of CD56-positive peripheral blood lymphocytes. Measurement of treatment-induced secondary cytokines showed significant increases in gamma-interferon serum levels in a proportion of patients tested, although with considerable interindividual variability. No significant increase in mean tumor necrosis factor-alpha levels was observed during rIL-2 treatment in vivo. The percentage of CD56-positive NK cells correlated with the clinical outcome of rIL-2 therapy. Thus, partial or complete responders had an increase from a mean of 20% NK cells prior to therapy up to a mean of 40% after the first treatment course. In contrast, patients with progressive disease had a mean of 22 and 24% NK cells before and after treatment, respectively.


Overview in the clinical management of patients with seronegative villous atrophy.
Differential diagnosis and management of enteropathies found in the context of seronegative villous atrophy (VA) are still a clinical challenge. Although seronegative coeliac disease may be the most frequent cause of serology-negative VA, other conditions must be taken into account in the differential diagnosis of seronegative VA. The rarity of these enteropathies with frequent overlapping of histological features may result in misclassification of such patients as affected by a seronegative or a refractory form of coeliac disease with consequent inappropriate treatments and long-term morbidity. The aim of this review is to summarize the current knowledge and to provide an evidence base and practical algorithmic approach for the investigation and management of seronegative VA.


Qualitative study of decisions about infant feeding among women in east end of London.
To improve understanding of how first time mothers who belong to a socioeconomic group with particularly low rates of breast feeding decide whether or not to initiate breast feeding. Qualitative semistructured interviews early in pregnancy and 6-10 weeks after birth. Women's homes in east end of London. 21 white, low income women expecting their first baby were interviewed mostly at home, often with their partner or a relative. Two focus groups were conducted. Women who had regularly seen a relative or friend successfully breast feed and described this experience positively were more confident about and committed to breast feeding. They were also more likely to succeed. Exposure to breast feeding, however, could be either a positive or a negative influence on the decision to breast feed, depending on the context. Women who had seen breast feeding only by a stranger often described this as a negative influence, particularly if other people were present. All women knew that breast feeding has health benefits. Ownership of this knowledge, however, varied according to the woman's experience of seeing breast feeding. The decision to initiate breast feeding is influenced more by embodied knowledge gained from seeing breast feeding than by theoretical knowledge about its benefits. Breast feeding involves performing a practical skill, often with others present. The knowledge, confidence, and commitment necessary to breast feed may be more effectively gained through antenatal apprenticeship to a breastfeeding mother than from advice given in consultations or from books.


Performance evaluation of SBR treatment for nitrogen removal from tannery wastewater.
Performance of SBR treatment for nitrogen removal from tannery is evaluated for a wide range of wastewater temperature between 7 and 30 degrees C. A pilot-scale SBR unit fed with plain-settled wastewater is operated on site for this purpose. Effective nitrogen removal is sustained by adjustment of the sludge age from 28 to 5 days. Concentration profiles of nitrogen compounds within a selected complete SBR cycle during the steady state operation at different wastewater temperatures and sludge ages are evaluated by model simulation. System performance is also interpreted in terms of modeling and stoichiometric calculation. Additional nitrate loss was observed during aerobic period when the aeration intensity was reduced by the factor of 50%.


Comparison of the evolutional process of children with autism spectrum disorders in different language therapeutic interventions.
To analyze and compare the extension and the speed of the evolutional process of children with Autism Spectrum Disorders in direct and indirect interventions as opposed to only indirect intervention. The design of this study is a clinical trial. The sample was composed of 11 children diagnosed with Autism (n=6) and Asperger syndrome (n=5) by a multidisciplinary team, that attended specialized speech-language pathology therapy at the institution were the study was carried out. These children were randomly divided into two groups: Therapy Group (TG) - composed by six subjects receiving both direct and indirect intervention; and Orientation Group (OG) - constituted by five subjects receiving exclusively indirect intervention. It was used the Autism Behavior Checklist (ABC) to interview the mothers, and the Sample of Vocal Behavior (SVB), in three occasions: at the beginning of the intervention process (time 0), six months later (time 1) and 12 months later (time 2). It was observed greater speed and extension in the evolutional process of the TG Group, both in the analysis of the Autism Behavior Checklist (total and partial scores) and the Sample of Vocal Behavior, especially in the item Full Language. The performance of children with Asperger syndrome was considered more positive when compared to that of children with autism. There was greater evolution in younger children and with normal, mild, and moderate adaptive functioning. The tendency towards better performance of the children attending direct and indirect intervention showed that this association is fundamental in the therapeutic process of children with Autism Spectrum Disorders.


Use of technology in endodontics by undergraduate dental students in a south-eastern state of Brazil.
This study aimed to determine the level of incorporation of current technologies for endodontic treatment in undergraduate dentistry courses in a south-eastern state of Brazil. For data collection, a self-assessment-based online questionnaire was created using the "Google Forms" platform, consisting of 12 multiple-choice and a few open-ended questions. The questions were related to the use of current technologies for diagnosis, imaging, use of ultrasonics in endodontics, instrumentation, use of apex locator, microscopy, photodynamic therapy and thermoplastic techniques during endodontic treatment. The questionnaire was sent to 54 dental schools in Minas Gerais. The results show low technological incorporation during the various stages of endodontic treatment by undergraduate students in dentistry courses in Minas Gerais. Despite the availability of several technologies to help perform different stages of endodontic treatment, it was observed that most universities do not teach the use of these technologies. Additional studies are needed to correlate how the lack of incorporation of these technologies could impact on the quality of the endodontic learning for undergraduate students.


Plk2 Loss Commonly Occurs in Colorectal Carcinomas but not Adenomas: Relationship to mTOR Signaling.
Plk2 is a target of p53. Our previous studies demonstrated that with wild-type p53, Plk2 impacts mTOR signaling in the same manner as TSC1, and Plk2-deficient tumors grew larger than control. Other investigators have demonstrated that Plk2 phosphorylates mutant p53 in a positive feedback loop. We investigated Plk2's tumor suppressor functions in relationship to mTOR signaling. Archival specimens from 12 colorectal adenocarcinomas were stained for markers including Plk2, phosphorylated mTOR (serine 2448) and ribosomal S6 (Serine 235/236). We show that Plk2 is expressed in normal colon, with a punctate staining pattern in supranuclear cytoplasm. In colorectal adenocarcinoma, Plk2 demonstrates complete or partial loss of expression. Strong expression of phosphorylated mTOR is observed in the invasive front. Phosphorylated S6 expression partially correlates with phosphorylated mTOR expression but appears more diffuse in some cases. p53 and Ki67 expression is diffuse, in the subset of cases examined. In order to determine whether Plk2 is lost prior to the development of invasive cancer, 8 colon polyps from 6 patients were evaluated for Plk2 expression. All polyps are positive for Plk2. A Cancer Genome Atlas search identified Plk2 mutations to be infrequent in colorectal adenocarcinomas. Neither Plk2 methylation (in the gene body) nor copy number variations correlated with changes in mRNA expression levels. Loss of Plk2 expression along with accentuated expression of phosphorylated mTOR and phosphorylated S6 at the invasive front in some colorectal carcinomas is consistent with previous findings that an interaction between Plk2 and TSC1 / mTOR signaling molecules plays a role in tumor suppression. Plk2 protein expression is lost at the same stage in colorectal carcinogenesis as p53. The p53 dependence of Plk2 loss and tumor suppressor function in relationship to mTOR signaling may have therapeutic implications.


[Analysis of bronchoscope-guided tracheal intubation in 12 cases with coronavirus disease 2019 under the personal protective equipment with positive pressure protective hood].
Endotracheal intubation is an independent risk factor for respiratory infectious diseases. We conducted a retrospective study in 12 cases with COVID-19 who underwent endotracheal intubation at ICU of the Guangzhou eighth hospital from January 20 to February 10, 2020. The intubation procedure, anesthetic regimen, and complication were collected and analyzed. The 9 healthcare workers who involved in intubation received virus nucleic acid test and 14 days temperature monitoring. All 12 patients were successfully intubated under the guidance of bronchoscope, without any complications. Midazolam, Propofol and Morphine or fentanyl were used for sedation and analgesia, avoiding patients cough and agitated during the procedure. The 9 healthcare workers were protected under the Personal Protective Equipment(PPE) with positive pressure protective hood. The detection of oropharyngeal swab virus nucleic acid were negative in all 9 healthcare workers, none of them had fever or any respiratory symptoms. The PPE with positive pressure protective hood should be needed to perform bronchoscope-guided endotracheal intubation in patients with COVID-19, it could strengthen to protect healthcare workers from virus exposure.


Factors associated with hospital arrival time for stroke patients.
Patients who experience a sudden ischemic stroke can benefit from administration of intravenous tissue plasminogen activator (tPA) to reduce the resulting disability, yet few arrive in time to be eligible for tPA administration. The purpose of this study was to determine (a) the stroke warning signs that most commonly result in the decision to seek hospital care, (b) who makes the decision to seek hospital care, (c) the most common mode of transportation to the hospital, (d) hospital arrival time in relation to the onset of the first warning sign, and (e) factors most associated with hospital arrival time for stroke survivors. Using a descriptive, cross-sectional design, data from a convenience sample of 50 stroke survivors and/or their companions (family, friends, or others seeking hospital care for the patient) were obtained by face-to-face interview during the patient's hospital stay using a structured interview guide developed by the investigator. The most common stroke warning sign resulting in the decision to seek medical care was sudden confusion and trouble speaking or understanding speech, followed by sudden numbness or weakness on one side of the body. Patients themselves were the most common initiators of care, followed by spouses, other relatives, and others. A majority of patients arrived by ambulance, followed by private car or taxi. Only 28.9% of patients arrived at the hospital within 3 hours of the first warning sign, with the mean arrival time for the group being 330.4 minutes (5.5 hours). Mode of transportation and perceived adequacy of income were the only significant factors associated with hospital arrival time, with no significant interaction effects. Patients arriving by private car or taxi and those perceiving their incomes as comfortable had the longest arrival times, suggesting public education efforts also should target people from higher socioeconomic groups. The nonsignificant associations between hospital arrival time, warning signs, and other demographic characteristics of initiators suggest there may be other unmeasured behavioral factors that play a more important role in reducing hospital arrival time for stroke patients. Further study of additional factors associated with early hospital arrival time is recommended to support educational efforts for early stroke treatment and prevention.


Induction of systemic inflammation and thickening of subepicardiac arteries in an animal model of uremia.
Although renal dysfunction is a known risk factor for cardiovascular disease (CVD), there are few experimental studies investigating the cardiovascular consequences of this condition. To analyze the impact of the induction of renal dysfunction on biomarkers of cardiovascular risk and on the histology of subepicardial vessels. This experimental study involved thirty Wistar male rats, which were divided into two groups. One (chronic kidney disease - CKD group) underwent renal ablation, and the other (SHAM group) was submitted to kidney manipulation only. Both groups were followed up for eight weeks. During follow-up, serum levels of urea, phosphorus and TNF-α were measured. Heart tissue was processed for histological analysis. The CKD group had increased levels of urea and phosphorus, in comparison with the SHAM group. The levels of TNF-α were increased in the CKD group and undetectable in the SHAM group (p < 0.05). Thickness of the middle layer of the subepicardial vessels of the CKD group was significantly higher than that of the SHAM group (p = 0.011). Induction of renal dysfunction in rats increased the biomarkers of cardiovascular risk and led to a thickening of the subepicardial vessels when compared with normal controls.


Low-Income Mothers' Descriptions of Children's Injury-Related Events: A Discourse Analysis.
The purpose of this study was to examine how mothers with young children who were living in low-income households used discursive strategies to explain their children's injury and near-miss events. In-person interviews were conducted with 17 mothers and a discourse analytic approach was used to analyze the data. Mothers used a variety of discursive strategies to explain injury events including minimizing the nature of events and expressing tensions between responsibility and resistance. Mothers also described challenges related to predicting children's behavior and dealing with competing demands. These discursive strategies reflected how societal expectations that mothers are held to in terms of keeping children safe conflicted at times with the constraints experienced by mothers living in economically challenging situations. The findings can be used to inform the design of injury prevention strategies that are sensitive to experiences of mothers of young children who are living with economic challenges.


[Biological cycles in the egg-layering by aquatic cave-dwelling crustacea].
In the populations of aquatic troglobitic Crustacea, breeding females are found all year round, with an annual peak. Data about their biological cycle suggest four phases of reproduction per year. Synchronisation of egg-laying (for the fraction of females actually reproducing) seems to happen for several species of Crustacea both in nature and at the laboratory. The onset of reproduction is sharpest either late winter or mid-spring, and its amplitude decreases along the annual cycle. The existence of a seasonal trigger is probable.


Pregnancy-dependent growth of mammary tumors is associated with overexpression of insulin-like growth factor II.
We demonstrate that although IGF-II gene expression is approximately 3-fold higher in 9,10-dimethyl-1,2-benzanthracine (DMBA)-induced rat mammary tumors (MTs) than in nonneoplastic breast tissue, IGF-II mRNA abundance in DMBA-induced MTs is approximately 130-fold higher in pregnant as compared to nonpregnant hosts. This correlated with accelerated tumor growth in pregnant hosts. Immunohistochemical studies of DMBA-induced MTs with an anti-IGF-II antibody showed an intense staining of tumor cells for IGF-II, whereas a very low staining signal was observed for normal epithelial cells in the lobules. A similar immunostaining pattern was observed in three of three human ductal cancers and adjacent normal breast tissue obtained during pregnancy. DMBA-induced MTs expressed high levels of type I receptor for IGFs as determined by Northern blots. In vitro studies confirmed that IGF-II is a mitogen for neoplastic epithelial cells derived from DMBA-induced MTs. These results demonstrate that hormonal changes associated with pregnancy accelerate breast cancer cell proliferation in the DMBA-induced MT model and suggest that this acceleration is mediated by up-regulation of IGF-II expression within neoplasms.


Testing equivalence of mediating models of income, parenting, and school readiness for white, black, and Hispanic children in a national sample.
This paper examines complex models of the associations between family income, material hardship, parenting, and school readiness among White, Black, and Hispanic 6-year-olds, using the Early Childhood Longitudinal Study-Kindergarten Cohort (ECLS-K). It is critical to test the universality of such complex models, particularly given their implications for intervention, prevention, and public policy. Therefore this study asks: Do measures and models of low income and early school readiness indicators fit differently or similarly for White, Black, and Hispanic children? Measurement equivalence of material hardship, parent stress, parenting behaviors, child cognitive skills, and child social competence is first tested. Model equivalence is then tested by examining whether category membership in a race/ethnic group moderates associations between predictors and young children's school readiness.


Co-operative effect of glutathione depletion and selenium induced oxidative stress on API and NFkB expression in testicular cells in vitro: insights to regulation of spermatogenesis.
Previous studies have shown that transcription factors, API and NFkB exert important roles in the process by which selenium regulates spermatogenesis. Glutathione, an intracellular thiol, acts as a source of reducing power and aids in maintenance of the cellular redox status. The activities of selenium are closely related to the availability of glutathione. Presently, mouse testicular cells were cultured in the presence of BSO, a known glutathione depletor, to generate oxidative stress. Selenium (Se) was added as sodium selenite to these cells at concentrations of 0.5 microM and 1.5 microM. It was observed that at 1.5 microM, Se acted as a pro-oxidant and significantly decreased the redox ratio. RT PCR analysis revealed that cjun, cfos expression increased in testicular cells cultured with Se compared to control. However, the major outcome was that the combined effect of Se supplementation and GSH depletion resulted in reduced expression of cjun and cfos while p65 expression increased. This suggests that selenium affects both these transcription factors differently. Our study indicates that though low levels of oxidative stress generated by moderate doses of selenium augments the expression of cjun and cfos, a robust increase in the ROS generation caused by the dual effect high levels of selenium and glutathione depletion leads to decrease in the expression of these genes. The present work substantiates our in vivo experiments and indicates the detrimental effect of excess selenium supplementation on male fertility.


Youth masculinities: compelling male heterosexuality.
This article seeks to extend understandings of heterosexual masculine identities through an examination of young men's constructions of what motivates young men to engage in heterosexual practices and relationships, and what not having sex might mean for them. Using the masculinity literature and work on heterosexuality to frame the discussion and to contextualize the findings, it explores the complex dynamics that frame the relationship between masculinity and heterosexuality. Specifically, how dominant or 'hegemonic' discourses of heterosexuality shape young men's identities, beliefs and behaviour. It considers these questions using empirical data from a qualitative study of young people living in close-knit working-class communities in the North East of England, with a specific focus on cultural and social attitudes towards sexuality and sexual practices. Peer group networks are a key site for the construction and (re)production of masculinity and, therefore, an important arena within which gendered social approval and acceptance is both sought and gained. In this article, I explore the reasons why young men engage in specific types of heterosexual practice in order to gain social approval. A central question is the extent to which heterosexuality is compelling for young men. That young men do feel compelled to behave in certain ways sexually, behaviours that they may be uncomfortable with and/or dislike, and the fact that they feel they are restricted in terms of how they can talk about their experiences within their peer group networks, demonstrates the power of dominant discourses of masculinity in everyday life. This is addressed through an examination of the restrictive effects of normative discourses about male heterosexuality, including their privatizing effects, which suggest that youth masculinities are often experienced in ways that are highly contradictory requiring young men to adopt a range of strategies to deal with this.


Health, disability & parental interests: adopting a contextual approach in the reproductive torts.
Illustrating the limitations of the notion that caring for a disabled child is harmful and sufficiently distinctive from the (judicially viewed harmless) experience of caring for non-disabled children, this article takes issue with the differential outcomes of the reproductive torts where success pivots upon the presence or absence of disability. Since caring for any child must be seen as bringing about a significant caring responsibility, if there is a difference in the burden that results, this will be a matter of extent, not kind. Also taking a critical view of the House of Lords recent determination of Rees v Darlington Memorial Hospital, this article notes that nor can a "common approach" to all claims of wrongful conception and birth offer an equitable alternative. Ignoring context and treating all reproductive outcomes equally for the purposes of compensation is certain to result in manifest unfairness. The thrust of the argument is that it is essential that the law embrace a more contemporary and contextual approach, based on the value of reproductive autonomy.


Effects of cognate status on word comprehension in second language learners: an ERP investigation.
ERPs were used to explore the different patterns of processing of cognate and noncognate words in the first (L1) and second (L2) language of a population of second language learners. L1 English students of French were presented with blocked lists of L1 and L2 words, and ERPs to cognates and noncognates were compared within each language block. For both languages, cognates had smaller amplitudes in the N400 component when compared with noncognates. L1 items that were cognates showed early differences in amplitude in the N400 epoch when compared with noncognates. L2 items showed later differences between cognates and noncognates than L1 items. The results are discussed in terms of how cognate status affects word recognition in second language learners.


Whole genome amplification of single epithelial cells dissociated from snap-frozen tissue samples in microfluidic platform.
Single cell sequencing is a technology capable of analyzing the genome of a single cell within a population. This technology is mostly integrated with microfluidics for precise cell manipulation and fluid handling. So far, most of the microfluidic-based single cell genomic studies have been focused on lab-cultured species or cell lines that are relatively easy to handle following standard microfluidic-based protocols without additional adjustments. The major challenges for performing single cell sequencing on clinical samples is the complex nature of the samples which requires additional sample processing steps to obtain intact single cells of interest without using amplification-inhibitive agents. Fluorescent-activated cell sorting is a common option to obtain single cells from clinical samples for single cell applications but requires >100 000 viable cells in suspension and the need for specialized laboratory and personnel. In this work, we present a protocol that can be used to obtain intact epithelial cells from snap-frozen postsurgical human endometrial tissues for single cell whole genome amplification. Our protocol includes sample thawing, cell dissociation, and labeling for genome amplification of targeted cells. Between 80% and 100% of single cell replicates lead to >25 ng of DNA after amplification with no measurable contamination, sufficient for downstream sequencing.


Lung nodule classification using deep Local-Global networks.
Lung nodules have very diverse shapes and sizes, which makes classifying them as benign/malignant a challenging problem. In this paper, we propose a novel method to predict the malignancy of nodules that have the capability to analyze the shape and size of a nodule using a global feature extractor, as well as the density and structure of the nodule using a local feature extractor. We propose to use Residual Blocks with a 3 × 3 kernel size for local feature extraction and Non-Local Blocks to extract the global features. The Non-Local Block has the ability to extract global features without using a huge number of parameters. The key idea behind the Non-Local Block is to apply matrix multiplications between features on the same feature maps. We trained and validated the proposed method on the LIDC-IDRI dataset which contains 1018 computed tomography scans. We followed a rigorous procedure for experimental setup, namely tenfold cross-validation, and ignored the nodules that had been annotated by < 3 radiologists. The proposed method achieved state-of-the-art results with AUC = 95.62%, while significantly outperforming other baseline methods. Our proposed deep Local-Global network has the capability to accurately extract both local and global features. Our new method outperforms state-of-the-art architecture including Densenet and Resnet with transfer learning.


Psychometric properties of the Food Environment Assessment Survey Tool (FEAST) in people with mobility impairment.
Approximately one in ten adults under the age of 65 in the USA has a mobility impairing disability. People with mobility impairment generally have poorer dietary habits contributing to obesity and related negative health outcomes. This article presents the psychometric properties of the Food Environment Assessment Survey Tool (FEAST) instrument that measures barriers to accessing healthy food from the perspective of people with mobility impairment (PMI). The current study presents cross-sectional data from two sequential independent surveys. Surveys were administered online to a national sample of PMI. Participants represented PMI living throughout the USA. The pilot FEAST survey involved 681 participants and was used to shape the final instrument; 25 % completed a retest survey. After following empirically and theoretically guided item reduction strategies, the final FEAST instrument was administered to a separate sample of 304 PMI. The final twenty-seven-item FEAST instrument includes items measuring Neighbourhood Environment, Home Environment, Personal Control and Access to Support (Having Help, Food Delivery Services, Parking/Transportation). The final four scales had acceptable intra-class correlations, indicating that the scales could be used as reliable measures of the hypothesised constructs in future studies. The FEAST instrument is the first of its kind developed to assess the food environment from the perspective of PMI themselves. Future studies would benefit from using this measure in research and practice to help guide the development of policy aimed at improving access to healthy food and promoting healthy eating in community-dwelling PMI.


A photoswitchable fluorescent protein for hours-time-lapse and sub-second-resolved super-resolution imaging.
Reversibly photoswitchable fluorescent proteins (RSFPs) are a class of fluorescent proteins whose fluorescence can be turned on and off by light irradiation. RSFPs have become essential tools for super-resolution (SR) imaging. Because most SR imaging techniques require high-power-density illumination, mitigating phototoxicity in cells due to intense light irradiation has been a challenge. Although we previously developed an RSFP named Kohinoor to achieve SR imaging with low phototoxicity, the photoproperties were insufficient to move a step further to explore the cellular dynamics by SR imaging. Here, we show an improved version of RSFP, Kohinoor2.0, which is suitable for SR imaging of cellular processes. Kohinoor2.0 shows a 2.6-fold higher fluorescence intensity, 2.5-fold faster chromophore maturation and 1.5-fold faster off-switching than Kohinoor. The analysis of the pH dependence of the visible absorption band revealed that Kohinoor2.0 and Kohinoor were in equilibria among multiple fluorescently bright and dark states, with the mutations introduced into Kohinoor2.0 bringing about a higher stabilization of the fluorescently bright states compared to Kohinoor. Using Kohinoor2.0 with our SR imaging technique, super-resolution polarization demodulation/on-state polarization angle narrowing, we conducted 4-h time-lapse SR imaging of an actin filament network in mammalian cells with a total acquisition time of 480 s without a noticeable indication of phototoxicity. Furthermore, we demonstrated the SR imaging of mitochondria dynamics at a time resolution of 0.5 s, in which the fusion and fission processes were clearly visualized. Thus, Kohinoor2.0 is shown to be an invaluable RSFP for the SR imaging of cellular dynamics.