Usefulness of Child HCAHPS Survey Data for Improving Inpatient Pediatric Care Experiences.
Quality improvement (QI) requires data, indicators, and national benchmarks. Knowledge about the usefulness of Child Hospital Consumer Assessment of Healthcare Providers and Systems (Child HCAHPS) data are lacking. We examined quality leader and frontline staff perceptions about patient experience measurement and use of Child HCAHPS data for QI. We surveyed children's hospital leaders and staff about their use of Child HCAHPS for QI, including measures from other studies. We compared scale and item means for leaders and staff and compared means to other studies. Almost all leaders, but only one-third of staff, received reports with Child HCAHPS data. Leaders found the data more useful for comparisons to other hospitals than did staff. Both agreed on the validity of Child HCAHPS scores and used these data for improving pediatric care experiences. They agreed the data accurately reflect their hospital's quality of care, provide specific information for QI, and can be used to improve pediatric care experiences. They also agreed on approaches to improve Child HCAHPS scores. Among staff, QI was reported as essential to their daily work and that Child HCAHPS data were integral to QI. As uptake of the Child HCAHPS survey increases, our study of one medium-sized, urban children's hospital revealed that leaders and staff believe Child HCAHPS provides actionable metrics for improvement. Our study fills a gap in research about the use of Child HCAHPS for pediatric QI. A multisite evaluation would provide further information about how the Child HCAHPS survey can improve care.


Silicon analogues of the retinoid agonists TTNPB and 3-methyl-TTNPB, disila-TTNPB and disila-3-methyl-TTNPB: chemistry and biology.
Twofold sila-substitution (C/Si exchange) in the saturated ring of the tetrahydronaphthalene skeleton of the retinoid agonists TTNPB (1 a) and 3-methyl-TTNPB (2 a) leads to disila-TTNPB (1 b) and disila-3-methyl-TTNPB (2 b), respectively. The silicon compounds 1 b and 2 b were synthesized in multiple steps, and their identities were established by elemental analyses, multinuclear NMR experiments, and single-crystal X-ray diffraction studies. Like TTNPB (1 a) and 3-methyl-TTNPB (2 a), the analogous silicon-based arotinoids 1 b and 2 b are strong pan-RAR agonists and display the same strong differentiation and apoptosis-inducing activity in NB4 promyelocytic leukemia cells as the parent carbon compounds. These results are in keeping with the nearly isomorphous structures of 1 a and 1 b bound to the complex of the RARbeta ligand-binding domain with the nuclear receptor (NR) box 2 peptide of the SRC-1 coactivator. The contacts within the ligand-binding pocket are identical except for helix H11, for which two turns are shifted in the disila-TTNPB (1 b) complex. This study represents the first comprehensive structure-function analysis of a carbon/silicon switch in a signaling molecule and demonstrates that silicon analogues can have the same biological functionalities and conserved structures as their parent carbon compounds, and it illustrates at the same time that silicon analogues of biologically active compounds have the potential to induce alternative allosteric effects, as in the case of helix H11, which might allow for novel options in drug design.


Investigation of Basophil Activation Test for Diagnosing Milk and Egg Allergy in Younger Children.
In children with concomitant food allergy and atopic dermatitis (AD), uncovering the causative food allergen is more arduous. We evaluated the basophil activation test (BAT) for its diagnostic value in children, including those with AD, for milk or egg allergy. We simultaneously measured serum-specific immunoglobulin E (sIgE) levels and performed BATs for cow's milk and egg white. We compared their overall diagnostic performance using the area under the receiver operating characteristic curve (AUC) with the Delong method and compared them in children with AD. Analyses were completed for 75 children for milk allergy and for 85 children for egg allergy. The sIgE and percentage of basophils with the expression of CD63 were correlated for both milk (r = 0.384, p < 0.001) and egg (r = 0.557, p < 0.001). The AUC of sIgE (0.701) for milk allergy was significantly increased when combined with the BAT (0.805; p = 0.029). In children with AD, the AUC of the BAT (0.924) for milk allergy was significantly larger than that of sIgE (0.701; p = 0.017). The BAT is a potentially useful diagnostic tool for milk allergy in children when combined with sIgE. Moreover, it may be a surrogate marker for milk allergy in children with AD.


Structural studies examining the substrate specificity profiles of PC-PLC(Bc) protein variants.
The phosphatidylcholine preferring phospholipase C from Bacillus cereus (PC-PLC(Bc)) catalyzes the hydrolysis of phospholipids in the following order of preference: phosphatidylcholine (PC)>phosphatidylethanolamine (PE)>phosphatidylserine (PS). In previous work, mutagenic, kinetic, and crystallographic experiments suggested that varying the amino acids at the 4th, 56th, and 66th positions had a significant influence upon the substrate specificity profile of PC-PLC(Bc). Here, we report the crystal structures of the native form of several PC-PLC(Bc) variants that exhibited altered substrate specificities for PC, PE, and PS at maximum resolutions of 1.90-2.05 Angstrom. Comparing the structures of these variants to the structure of the wild-type enzyme reveals only minor differences with respect to the number and location of active site water molecules and the side chain conformations of residues at the 4th and 56th positions. These results suggest that subtle changes in steric and electronic properties in the substrate binding site of PC-PLC(Bc) are responsible for the significant changes in substrate selectivity.


Three-year haemodynamic performance of the St Jude Trifecta bioprosthesis.
To examine the haemodynamic performance of the St Jude Trifecta valve for aortic valve replacement (AVR) at 3 years after implantation. In a single-centre, prospective, observational, independent study, we enrolled 122 patients who had AVR using a Trifecta bioprosthesis in the July 2010-June 2011 period. A clinical and echocardiographic in-house follow-up was scheduled. In our series, 14.7% of patients received a 19-mm, 28.7% had a 21-mm, 35.2% had a 23-mm and 21.3% had a greater-size prosthesis. There were no cases of operative mortality or of valve-related complications both early and at follow-up (except one sudden unexplained death). Completeness of the 3-year echocardiographic follow-up was 80% among survivors. The average mean transvalvular gradient (mTVG) at 3 years was 14.2, 10.8, 8.6, 7.1 and 6.8 mmHg (sizes 19 to 27/29, respectively). There was no statistically significant difference between average mTVGs measured immediately after implantation versus at the 3-year follow-up in the overall population. The average peak transvalvular gradient (pTVG) at 3 years was 25, 20, 16.8, 13.9 and 14.4 mmHg (sizes 19 to 27/29, respectively). The average indexed effective orifice area (iEOA) at 3 years was 0.8, 0.9, 1, 1.3 and 1.3 cm(2)/m(2) (sizes 19-27, respectively). The rate of moderate patient-prosthesis mismatch (PPM) at 3 years was 15.7%; there were two instances of severe PPM (2.2%). All cases of PPM occurred in the 19, 21 and 23 mm size subgroups. The Trifecta valve retains its excellent haemodynamic properties at the 3-year follow-up. The rate of PPM is considerably low.


[Epidemiology of childhood tumors in the Piedmont and Valle d'Aosta regions during the 1965-69 period].
Piemonte and Valle d'Aosta are in the NW part of Italy. In 1967 total population and population aged 0-14 were respectively 4.338.000 and 841.000. During the period 1965-69 a total of 688 cases of cancer (including leukemia) were diagnosed inchildren under 15 years of age resident in this area. The Cancer Registry of Piedmont and Valle d'Aosta (RTP) provided information on 465 children; the other 223 were collected through additional investigation in the files of 31 university of hospital departments of the region and 5 extraregional hospitals. Distribution through the 5 years covered by the investigation is shown in Table 1. Histological or hematological confirmation of the diagnosis was available in 499 cases (73%). The 688 cases included 216 leukemias, 131 tumors of the central nervous system, 40 neuroblastomas, 82 lymphomas (including 34 cases of Hodgkin's disease), 46 nephroblastomas, 32 soft-tissue sarcomas, 29 bone sarcomas (including 5 cases of Ewing's disease), 25 retinoblastomas, 12 thyroid tumors, 10 extragenital teratomas, 5 ovarian dysgerminomas, 4 tumours of the testes, 4 hepatoblastomas and 52 other tumours (Table 2). The number of children under 15 years of age dying of cancer during 1965-69 was 341 (Table 2). Incidence and mortality rates by age groups are given in Tables 3 and 4. The rates were of the same order as those observed in the U.S. and in other European cancer registries during the same period (Tables 4,5 and 6). The mortality rate for nephroblastomas at age 0-4 was 1,09/100.000/year, i.e. slightly higher than that observed in the U.S. in 1960 but about twice as high as that observed in the U.S. in 1967 (14). Incidence and mortality rates for both Hodgkin's and non-Hodgkin's lymphomas were about 3 times higher in males than in females (Table 3). The difference was less obvious during the first five years of life, in which the total number of diagnosed lymphomas was 16.


Participation of proteasome-ubiquitin protein degradation in autophagy and the activation of AMP-activated protein kinase.
Although activation of the AMP-activated protein kinase (AMPK) as well as of ubiquitin/proteasome degradative pathways play an essential role in the preservation of metabolic homeostasis, little is known concerning interactions between protein turnover and AMPK activity. In the present studies, we found that inhibition of the 26S proteasome resulted in rapid activation of AMPK in macrophages, epithelial and endothelial cells. This was associated with increased levels of non-degraded Ub-protein conjugates, in both cytosolic and mitochondrial fractions. Selective inhibitors of ubiquitination or siRNA-dependent knockdown of Ub-ligase E1 diminished AMPK activation in cells treated with MG132, a 26S proteasome inhibitor. In addition to inhibition of AMPK activation by Ub-ligase E1 inhibitors, deficiency in Park2 mitochondria-associated Ub-ligase E3 also reduced AMPK activation upon dissipation of mitochondrial membrane potential (Δψm). Accumulation of Ub-proteins was correlated with decreases in cellular bioenergetics, including mitochondria oxidative phosphorylation, and an increase in ROS formation. Antioxidants, such as N-acetyl-L-cysteine or mitochondria-targeted MitoTEMPO, effectively diminished MG132-induced AMPK activation. Glucose-dependent regulation of AMPK or AMPK-mediated autophagy was modulated by alterations in intracellular levels of Ub-protein conjugates. Our results indicate that accumulation of ubiquitinated proteins alter cellular bioenergetics and redox status, leading to AMPK activation.


Spreading depression and the clinical correlates of migraine.
Migraine is the most common neurologic condition. One-third of migraineurs experience transient neurologic symptoms, the so-called aura. There is strong evidence that spreading depression (SD) is the electrophysiologic substrate of migraine aura. SD is an intense pan-depolarization wave that slowly propagates in gray matter by way of contiguity and transiently disrupts neuronal function. When induced subcortically, striatal SD causes hemiparesis, hippocampal SD can trigger seizures and impact cognition, and bilateral thalamic SD can diminish consciousness. Recent data show that transgenic mice expressing familial hemiplegic migraine (FHM) type 1 mutations in voltage-gated Ca2+ channels (Cav2.1) develop mutation-specific aura-like signs after a cortical SD similar to patients with the respective mutation. These signs are associated with facilitated subcortical SD propagation. As in FHM, mice with the R192Q mutation develop pure hemiplegia associated with cortical SDs propagating into caudoputamen. S218L mice display additional signs such as seizures and coma when SD propagates into hippocampus and thalamus. In hyperexcitable FHM brains, SD may propagate between cortex and subcortical structures via permissive gray matter bridges, or originate de novo in subcortical structures, to explain unusual and severe aura signs and symptoms. Reciprocal spread and reverberating waves can explain protracted attacks.


Decreased cytokine-induced IgA subclass production by CD40-ligated circulating B cells in primary IgA nephropathy.
In IgA nephropathy (IgAN), the abnormalities in the IgA immune system are apparently restricted to the IgA1 subclass in the systemic compartment, as evidenced by the antigen-specific responses to recall antigens. Since precursors of IgA producing B cells in human peripheral blood belong predominantly to the mucosal compartment, we took the opportunity to assess the capacity of circulating B cells in peripheral blood (PBMC) of 20 IgAN patients and matched controls to produce IgA, IgA1, and IgA2. Supernatants from T cell- (immobilized anti-CD3) and B cell-specific (CD40 ligation) activated cultures were assessed for immunoglobulin isotypes by ELISA. In addition, we compared the sensitivity of T and B cells to various cytokines (IL-2, IL-10, TGF-beta) in both culture systems. In contrast to significantly higher plasma IgA1 levels (P < 0.01), no significant differences in salivary IgA1 (P = 0.73) and IgA2 (P = 0.96) levels or ratios (P = 0.91) were found. In the absence of exogenous cytokines, none of the different culture systems led to significant differences in IgA or IgA subclass synthesis by PBMCs of patients and controls. However, in IgAN patients, the addition of IL-2 did not enhance the production of the IgA subclasses as was found in controls. Furthermore IL-10 led to significantly (P < 0.05) lower IgA1 and IgA2 synthesis in patients than in controls. TGF-beta induced suppression of all isotypes in patients and controls. None of the different conditions resulted in a selectively enhanced production of any one of the IgA subclasses. When both IL-10 and TGF-beta were added to the cultures, IgM was the predominant immunoglobulin synthesized both in patients and controls with a significantly (P < 0.05) lower synthesis of IgM, IgG, IgA1, and IgA2 in patients. These in vitro data suggest that PBMCs from patients contain more mature and further differentiated B cells. However, there was no selective IgA or IgA1 dysregulation of circulating B cells in IgAN. These results do not confirm the widely believed paradigm that patients with IgAN are primary hyperresponders.


The Association Between MUC5B Mutations and Clinical Outcome in Patients with Rheumatoid Arthritis-Associated Interstitial Lung Disease: A Retrospective Exploratory Study in China.
BACKGROUND Patients with rheumatoid arthritis (RA) who develop interstitial lung disease (RA-ILD), show features of usual interstitial pneumonia (UIP) on high-resolution computed tomography (HRCT). This retrospective exploratory clinical study aimed to investigate the association between mutations in the MUC5B gene and clinical outcome in patients with RA, with or without RA-ILD, using whole-exome sequencing (WES). MATERIAL AND METHODS WES was performed using peripheral blood samples for mutations in the MUC5B gene in 51 patients diagnosed with RA without ILD, and 45 patients with RA-ILD. The cumulative incidence in acute exacerbations of RA-ILD and variables associated with acute exacerbations of RA-ILD were analyzed. RESULTS In patients with RA-ILD, the main genetic variants of MUC5B were identified, with an odds ratio (OR) of 3.410 (p=0.013). Nine patients with RA without ILD (17.6%) and 19 patients with RA-ILD (42.2%) expressed MUC5B variants. Patients with RA-ILD carrying MUC5B variants had a significantly increased duration of RA-ILD (p=0.03) and showed a UIP pattern on lung HRCT (p=0.01). Acute exacerbations of RA-ILD occurred in 25 patients during follow-up, including 13 patients with mutant MUC5B and 12 patients with wildtype MUC5B. Univariate analysis showed that MUC5B mutations (p=0.043), older age of onset of RA (p=0.041), increased serum anti-citrullinated protein antibodies (ACPAs) (p=0.033), and a UIP imaging pattern on HRCT (p=0.015) were significantly correlated with acute exacerbations of RA-ILD. However, these findings were not supported by multivariate analysis (p=0.065). CONCLUSIONS The carrier status of MUC5B variants was an indicator of reduced prognosis and increased exacerbations of RA-ILD.


The genetic aetiology of cannabis use initiation: a meta-analysis of genome-wide association studies and a SNP-based heritability estimation.
While initiation of cannabis use is around 40% heritable, not much is known about the underlying genetic aetiology. Here, we meta-analysed two genome-wide association studies of initiation of cannabis use with > 10 000 individuals. None of the genetic variants reached genome-wide significance. We also performed a gene-based association test, which also revealed no significant effects of individual genes. Finally, we estimated that only approximately 6% of the variation in cannabis initiation is due to common genetic variants. Future genetic studies using larger sample sizes and different methodologies (including sequencing) might provide more insight in the complex genetic aetiology of cannabis use.


TCR alpha beta+ CD4- CD8- T cells differentiate extrathymically in an lck-independent manner and participate in early response against Listeria monocytogenes infection through interferon-gamma production.
T-cell receptor (TCR) alpha beta+ CD4- CD8- (double-negative; DN) T cells appear in the peritoneal cavity at an early stage of intraperitoneal (i.p.) infection with the intracellular pathogen Listeria monocytogenes. In the present report, we analysed the developmental pathway and functions of the TCR alpha beta+ DN T cells using the L. monocytogenes infection system. The TCR alpha beta+ DN T cells appeared in the peritoneal cavity after L. monocytogenes i.p. infection in adult-thymectomized lethally irradiated bone marrow chimeras and p56lck-deficient mice. The results demonstrated that the TCR alpha beta+ DN T cells can develop extrathymically in a p56lck-independent manner. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that the TCR alpha beta+ DN T cells expressed genes for interferon-gamma (IFN-gamma), the macrophage chemotactic factors MCP-1 and Eta-1, and granulocyte-macrophage colony-stimulating factor (GM-CSF) but lacked expression of genes for interleukin-2 (IL-2), IL-4 and IL-10. As expected from the RT-PCR analysis, the TCR alpha beta+ DN T cells produced IFN-gamma in response to anti-TCR beta monoclonal antibody (mAb), anti-CD3 mAb and L. monocytogenes-infected macrophages but IL-4 was undetectable after the stimulation. Furthermore, the intracellular cytokine staining analysis demonstrated that approximately half of the TCR alpha beta+ DN T cells detectable at the early stage of L. monocytogenes infection were IFN-gamma-producing cells. All of the results suggest that the TCR alpha beta+ DN T cells develop through a unique extrathymic p56lck-independent pathway and participate in early protection against bacterial infection through activation and accumulation of macrophages.


[Newcastle disease in southern Chad: peak epidemic periods and the impact of vaccination].
In spite of its universally acknowledged importance, backyard chicken production is still being hampered by Newcastle disease in some parts of the world. In Chad, the disease has been reported almost everywhere in the country and confirmed in several regions, but there are no control measures in place. A survey was conducted at three sites in south-eastern Chad in July and August 2001, based on face-to-face interviews with 20% of the peasant farmers keeping chickens at these sites. The aim was to collect information on peak epidemic periods and on ways in which the infection spreads. The survey revealed that the peak epidemic periods for Newcastle disease are April, during the mango harvesting and selling period, and December, when trade increases for the seasonal festivities. The survey also showed that peasant farmers attach great importance to chicken farming. The survey was followed by a vaccination trial in November 2001 and February 2002, using the La Sota strain administered ocularly. All of the birds vaccinated during the trial were successfully protected from the disease and both chicken production and the income of the villagers increased. The authors conclude that in order to sustain poultry farming and maximise production in the southern zone, vaccination programmes must be urgently introduced, campaigns to raise awareness of Newcastle disease should be carried out and financial support to pay for vaccines should be provided. Efforts to combat other causes of poultry mortality must also be undertaken.


Evidence for acquired pregenual anterior cingulate gray matter loss from a twin study of combat-related posttraumatic stress disorder.
Controversy exists over the nature and origin of reduced regional brain volumes in posttraumatic stress disorder (PTSD). At issue is whether these reductions represent preexisting vulnerability factors for developing PTSD upon traumatic exposure or acquired PTSD signs due to the traumatic stress that caused the PTSD or the chronic stress of having the disorder (or both). We employed a case-control design in monozygotic twin pairs discordant for combat exposure to address the preexisting versus acquired origin of brain morphometric abnormalities in PTSD. We used voxel-based morphometry to search for gray matter density reductions in magnetic resonance imaging (MRI) data obtained in a previous study of combat-exposed Vietnam veteran twins with (n = 18) versus without (n = 23) PTSD and their "high-risk" versus "low-risk" (respectively) identical combat-unexposed cotwins. Compared with the combat-exposed twins without PTSD, the combat-exposed twins with PTSD showed significant gray matter density reductions in four predicted brain regions: right hippocampus, pregenual anterior cingulate cortex (ACC), and left and right insulae. There was a significant PTSD Diagnosis x Combat Exposure interaction in pregenual ACC in which combat-exposed PTSD twins had lower gray matter density than their own combat-unexposed cotwins as well as than the combat-exposed twins without PTSD and their cotwins. The results point to gray matter volume diminutions in limbic and paralimbic structures in PTSD. The pattern of results obtained for pregenual ACC suggests that gray matter reduction in this region represents an acquired sign of PTSD consistent with stress-induced loss.


Identification and antibacterial resistance of bacteria isolated from poultry.
Food-borne infections are among the prominent health hazards. Antibacterial agents (ABA) are usually administered to poultry in Lebanon as antibiotic growth promoters (AGP), which might lead to the dissemination of resistant bacterial strains. The aims of this study were to isolate potential food borne pathogens from poultry and investigate an association between AGP usage and antibacterial resistance (ABR). Isolates were obtained from the culture of cloacae swabs and identified. Escherichia coli was the predominant isolate. There was a significant association between the use of tetracycline and gentamicin as AGP and the number of E. coli isolates resistant to these ABA.


Parent-reported feeding and swallowing difficulties of children with Autism Spectrum Disorders (aged 3 to 5 years) compared to typically developing peers: a South African study.
Research on aspects of neurodevelopment such as feeding and swallowing difficulties in children with Autism Spectrum Disorders (ASD) is limited in low and middle income countries such as South Africa. A descriptive comparative group design was used to investigate feeding and swallowing difficulties of young children with ASD in comparison to typically developing peers. The Brief Autism Mealtime Behavioural Inventory (BAMBI) was used. Findings indicated a significant difference in the severity of feeding and swallowing difficulties between the two groups. Difficulties such as food selectivity, sensory processing difficulties, oral-motor difficulties and symptoms of dysphagia were identified. The findings added to the existing global literature on feeding and swallowing difficulties in young children with ASD but provide a unique first perspective on these difficulties in South African children with ASD. Findings also highlighted the use of the BAMBI as an adjunct clinical tool to encourage comprehensive parental report during feeding assessment in this population. Cultural adaptation of the BAMBI for future use in African countries should be considered. A better local understanding of the parental perspective on the multidimensional nature of the feeding and swallowing difficulties displayed by young children with ASD was obtained.


Molecular insight into how the position of an abasic site modifies DNA duplex stability and dynamics.
Local perturbations to DNA base-pairing stability from lesions and chemical modifications can alter the stability and dynamics of an entire oligonucleotide. End effects may cause the position of a disruption within a short duplex to influence duplex stability and structural dynamics, yet this aspect of nucleic acid modifications is often overlooked. We investigate how the position of an abasic site (AP site) impacts the stability and dynamics of short DNA duplexes. Using a combination of steady-state and time-resolved spectroscopy and molecular dynamics simulations, we unravel an interplay between AP-site position and nucleobase sequence that controls energetic and dynamic disruption to the duplex. The duplex is disrupted into two segments by an entropic barrier for base-pairing on each side of the AP site. The barrier induces fraying of the short segment when an AP site is near the termini. Shifting the AP site inward promotes a transition from short-segment fraying to fully encompassing the barrier into the thermodynamics of hybridization, leading to further destabilization of the duplex. Nucleobase sequence determines the length scale for this transition by tuning the barrier height and base-pair stability of the short segment, and certain sequences enable out-of-register base-pairing to minimize the barrier height.


Cortisol kinetics and fluid distribution in brook trout (Salvelinus fontinalis).
Cortisol kinetics were examined in brook trout (Salvelinus fontinalis) to assess possible relationships with body fluid distribution during acclimation to sea water (SW). The disappearance curve of [3H]cortisol in plasma, after a bolus injection, was analysed by compartmental analysis using a three-pool mammillary model. The results indicated that only approximately 10% of the total exchangeable cortisol was located in the plasma pool. Over 75% of the total cortisol was associated with a large slowly exchanging pool and the remaining cortisol was located in a second extravascular tissue pool which was in rapid exchange with the plasma pool. Two days after transfer of trout from fresh water to SW, when plasma chloride concentration was at a new steady state, body weight, intracellular fluid volume, haematocrit and inulin clearance rate were lowered but plasma, blood and extracellular volumes were unaltered. Cortisol plasma clearance rate was unaltered but plasma cortisol concentration, cortisol secretion rate, total cortisol pool size and interpool transport rates were increased. These results are consistent with an acute role for cortisol in SW adaptation of brook trout. The fraction of the total cortisol cleared was smaller and the average time that cortisol spent in the tissue pools was slightly longer in trout after transfer to SW, possibly reflecting altered fluid dynamics. The fractional disappearance rate was larger at higher plasma cortisol concentrations in the SW trout. This relationship is compatible with the hypothesis that cortisol protein binding protects cortisol from metabolism.


On the cellular convexity of complexes.
In this paper we discuss cellular convexity of complexes. A new definition of cellular convexity is given in terms of a geometric property. Then it is proven that a regular complex is celiularly convex if and only if there is a convex plane figure of which it is the cellular image. Hence, the definition of cellular convexity by Sklansky [7] is equivalent to the new definition for the case of regular complexes. The definition of Minsky and Papert [4] is shown to be equivalent to our definition. Therefore, aU definitions are virtually equivalent. It is shown that a regular complex is cellularly convex if and only if its minimum-perimeter polygon does not meet the boundary of the complex. A 0(n) time algorithm is presented to determine the cellular convexity of a complex when it resides in n × m cells and is represented by the run length code.


Contemporary results after sapheno-popliteal bypass for chronic femoral vein occlusion.
Chronic occlusion of the femoral or the proximal popliteal vein responsible for venous obstruction and the constellation of clinical sequelae that ensue remains a surgical challenge that carries notable patient morbidity. Sapheno-popliteal bypass (SPB) remains a surgical reconstructive option for select patients that demonstrate patency of the popliteal vein, great saphenous vein, saphenofemoral junction, and iliac veins. We sought to analyze our single-institution experience with this technique. A retrospective review of a single-center experience with SPB was performed. Preoperative risk factors and indications for intervention (ie, venous claudication, ulceration) were identified. Duration of follow-up and endpoints, including clinical improvement, wound healing, patency, and limb loss were assessed. A Kaplan-Meier analysis for primary and secondary patency was performed. Seventeen patients underwent SPB for chronic lower extremity venous obstruction between July 1988 and August 2011. Median age at operation was 41 years (range, 23-69 years). There was a male predominance noted (n = 12; 71%). All patients had chronic edema and venous claudication. Five patients (29%) had evidence of venous ulceration preoperatively. Eight patients (47%) underwent a preceding venous intervention (ie, iliac stenting or venous thrombolysis). Three patients had a concomitant arteriovenous fistula, created at the time of bypass to enhance in-flow; three patients underwent concomitant femoral-femoral venous bypass. Four patients (24%) experienced hematoma postoperatively that required operative evacuation; in two patients, compression from this hematoma resulted in early graft occlusion. After a median follow-up of 103 months (range, 3-271 months), 82% of patients experienced near or complete resolution of venous claudication. Three of the five patients with venous ulceration healed their wounds (67%). Of the 16 patients that underwent Duplex scan follow-up, primary patency after a median follow-up of 103 months was 56%, primary-assisted patency was 69%, and secondary patency was 75%. One patient required amputation approximately 21 years after SPB and there were no deaths. This secondary patency rate exceeds previously published patency rates. SPB may be indicated for certain patients with chronic venous stasis disease secondary to femoral venous obstruction that have failed other standard therapies. SPB remains a satisfactory and reliable procedure that produces clinical improvement in a selected group of patients and should be considered in a contemporary venous surgical practice.


Percolation framework to describe El Niño conditions.
Complex networks have been used intensively to investigate the flow and dynamics of many natural systems including the climate system. Here, we develop a percolation based measure, the order parameter, to study and quantify climate networks. We find that abrupt transitions of the order parameter usually occur ∼1 year before El Niño events, suggesting that they can be used as early warning precursors of El Niño. Using this method, we analyze several reanalysis datasets and show the potential for good forecasting of El Niño. The percolation based order parameter exhibits discontinuous features, indicating a possible relation to the first order phase transition mechanism.


Current state of continuous ambulatory peritoneal dialysis in Egypt.
Patients with end-stage renal disease (ESRD) continue to increase in number worldwide, especially in developing countries. Although continuous ambulatory peritoneal dialysis (CAPD) has comparable survival advantages as hemodialysis (HD), it is greatly underutilized in many regions worldwide. The prevalence of use of CAPD in Egypt is 0.29/million population in 2017. The aim of this study is to describe the current state and practice of CAPD in Egypt and included 22 adult patients who were treated by CAPD. All the study patients were switched to CAPD after treatment with HD failed due to vascular access problems. Patients were mainly female (68.2 %) with the mean age of 49.77 ± 11.41 years. The average duration on CAPD was 1.76 ± 1.30 years. Hypertension was the main cause of end-stage renal disease (ESRD) constituting 36.4%, followed by diabetes (27.3 %), and toxic nephropathy (4.5%). Of importance is that about 31.8% of patients had ESRD of unknown etiology. The mean weekly Kt/V urea of patients on PD was 1.92 ± 0.18. The mean hemoglobin, serum calcium, phosphorus, parathormone, and albumin levels were 10.27 ± 1.98 g/dL, 8.36 ± 1.19 mg/dL, 5.70 ± 1.35 mg/dL, 541.18 ± 230.12 pg/mL, and 2.98 ± 0.73 g/dL, respectively. There was no significant difference between diabetic and nondiabetic CAPD patients regarding demographic and laboratory data. Our data indicate that there is continuing underutilization of CAPD in Egypt which may be related to nonavailability of CAPD fluid, patient factors (education and motivation), gradual decline of the efficiency of health-care professionals, and lack of a national program to start PD as the first modality for renal replacement therapy. It is advised to start an organized program to make CAPD widespread and encourage local production of PD fluids to reduce the cost of CAPD.


Improved InGaN/GaN light-emitting diodes with a p-GaN/n-GaN/p-GaN/n-GaN/p-GaN current-spreading layer.
This work reports both experimental and theoretical studies on the InGaN/GaN light-emitting diodes (LEDs) with optical output power and external quantum efficiency (EQE) levels substantially enhanced by incorporating p-GaN/n-GaN/p-GaN/n-GaN/p-GaN (PNPNP-GaN) current spreading layers in p-GaN. Each thin n-GaN layer sandwiched in the PNPNP-GaN structure is completely depleted due to the built-in electric field in the PNPNP-GaN junctions, and the ionized donors in these n-GaN layers serve as the hole spreaders. As a result, the electrical performance of the proposed device is improved and the optical output power and EQE are enhanced.


Nosocomial Outbreak of a Novel Extended-Spectrum β-Lactamase Salmonella enterica Serotype Isangi Among Surgical Patients.
OBJECTIVE Nosocomial outbreaks caused by Salmonella are rare. We describe the investigation and control of a cluster of novel extended-spectrum β-lactamase (ESBL) Salmonella enterica serotype Isangi in a hospital in southeastern Michigan. METHODS An epidemiologic investigation, including case-control study, assessment of infection control practices and environmental cultures, was performed to identify modes of transmission. Healthcare workers (HCWs) exposed to case patients were screened. Strain relatedness was determined using pulsed-field gel electrophoresis (PFGE); ESBL confirmation was conducted using real-time PCR. Control measures were implemented to prevent further transmission. RESULTS Between September 2 and October 22, 2015, 19 surgical patients, including 10 organ transplant recipients and 1 HCW, had positive S. Isangi cultures. Of these case patients and HCW, 13 had gastroenteritis, 2 had bacteremia, 1 had surgical-site infection, and 4 were asymptomatic. Pulsed-field gel electrophoresis (PFGE) showed 89.5% similarity among the isolates in these cases. Isolates with resistant-phenotypes possessed plasmid-mediated CTX-M15 ESBL. A total of 19 case patients were compared with 57 control participants. Case patients had significantly higher odds of exposure to an intraoperative transesophageal (TEE) probe (adjusted odds ratio 9.0; 95% confidence interval, 1.12-72.60; P=.02). Possible cross-transmission occurred in the HCW and 2 patients. Cultures of TEE probes and the environment were negative. The outbreak ended after removal of TEE probes, modification of reprocessing procedures, implementation of strict infection control practices, and enhanced environmental cleaning. CONCLUSIONS We report the first nosocomial ESBL S. Isangi outbreak in the United States. Multiple control measures were necessary to interrupt transmission of this gastrointestinal pathogen. Exposure to possibly contaminated TEE probes was associated with transmission. Periodic monitoring of reprocessing procedures of TEE probes may be required to ensure optimal disinfection. Infect Control Hosp Epidemiol 2016;37:954-961.


Polyphosphoinositides are enriched in plant membrane rafts and form microdomains in the plasma membrane.
In this article, we analyzed the lipid composition of detergent-insoluble membranes (DIMs) purified from tobacco (Nicotiana tabacum) plasma membrane (PM), focusing on polyphosphoinositides, lipids known to be involved in various signal transduction events. Polyphosphoinositides were enriched in DIMs compared with whole PM, whereas all structural phospholipids were largely depleted from this fraction. Fatty acid composition analyses suggest that enrichment of polyphosphoinositides in DIMs is accompanied by their association with more saturated fatty acids. Using an immunogold-electron microscopy strategy, we were able to visualize domains of phosphatidylinositol 4,5-bisphosphate in the plane of the PM, with 60% of the epitope found in clusters of approximately 25 nm in diameter and 40% randomly distributed at the surface of the PM. Interestingly, the phosphatidylinositol 4,5-bisphosphate cluster formation was not significantly sensitive to sterol depletion induced by methyl-beta-cyclodextrin. Finally, we measured the activities of various enzymes of polyphosphoinositide metabolism in DIMs and PM and showed that these activities are present in the DIM fraction but not enriched. The putative role of plant membrane rafts as signaling membrane domains or membrane-docking platforms is discussed.


Physician practices in the prevention of deep vein thrombosis: the MassPRO DVT Study.
Numerous well-designed clinical trials have demonstrated that prophylaxis reduces the incidence of acute deep vein thrombosis (DVT) in high-risk surgical patients by two-thirds, with a corresponding reduction in mortality from pulmonary embolism. However, studies of clinical practices suggest that DVT prophylaxis is underused-for example, only 39% of high-risk surgical patients in 16 central Massachusetts hospitals were administered DVT prophylaxis in 1986. Subsequently, an intensive educational initiative was launched to improve utilization of DVT prophylaxis. Although some improvement was reported, the level of use was not optimal. The Massachusetts Peer Review Organization (MassPRO) DVT study was designed to gather data on recent practice patterns among Massachusetts surgeons and determine the need for additional educational and quality assurance efforts. The results indicate that there is broad compliance among orthopedic surgeons with consensus recommendations for the use of DVT prophylaxis. Nearly all patients who undergo total hip replacement in Massachusetts are protected from DVT by one or more methods of prophylaxis. These data suggest that the ongoing efforts to improve the use of DVT prophylaxis in Massachusetts since 1986 have come to fruition, at least with respect to total hip replacement.


[A novel method of cystoplasty after cystectomy in cancer].
A new method of cystoplasty with free musculocutaneous graft on vascular crus was developed and introduced into clinical practice. This method satisfies the requirements necessary for artificial urinary bladder that are created from the segment of small intestine and considered as a "gold standard" in the treatment of such pathology. Good anatomic-and-functional results (urination way usual for the patient is remained, the volume of reservoir being created is sufficient, low urine pressure, anti-reflux mechanism and preservation of upper urinary tracts) permit to recommend the method for clinical study and use.


Central obesity in asymptomatic volunteers is associated with increased intrasphincteric acid reflux and lengthening of the cardiac mucosa.
In the West, a substantial proportion of subjects with adenocarcinoma of the gastric cardia and gastroesophageal junction have no history of reflux. We studied the gastroesophageal junction in asymptomatic volunteers with normal and large waist circumferences (WCs) to determine if central obesity is associated with abnormalities that might predispose individuals to adenocarcinoma. We performed a study of 24 healthy, Helicobacter pylori-negative volunteers with a small WC and 27 with a large WC. Abdominal fat was quantified by magnetic resonance imaging. Jumbo biopsy specimens were taken across the squamocolumnar junction (SCJ). High-resolution pH-metry (12 sensors) and manometry (36 sensors) were performed in upright and supine subjects before and after a meal; the SCJ was visualized fluoroscopically. The cardiac mucosa was significantly longer in the large WC group (2.5 vs 1.75 mm; P = .008); its length correlated with intra-abdominal (R = 0.35; P = .045) and total abdominal (R = 0.37; P = .034) fat. The SCJ was closer to the upper border of the lower esophageal sphincter (LES) in subjects with a large WC (2.77 vs 3.54 cm; P = .02). There was no evidence of excessive reflux 5 cm above the LES in either group. Gastric acidity extended more proximally within the LES in the large WC group, compared with the upper border (2.65 vs 4.1 cm; P = .027) and peak LES pressure (0.1 cm proximal vs 2.1 cm distal; P = .007). The large WC group had shortening of the LES, attributable to loss of the distal component (total LES length, 3 vs 4.5 cm; P = .043). Central obesity is associated with intrasphincteric extension of gastric acid and cardiac mucosal lengthening. The latter might arise through metaplasia of the most distal esophageal squamous epithelium and this process might predispose individuals to adenocarcinoma.


[Characteristics of medical use of Korvazan® for restorative treatment of patients with myocardial infarction, counting the risk factors].
The largest contribution to mortality from cardiovascular diseases belongs risk factors for cardiovascular events. In order to determine the effectiveness of rehabilitation patients undergoing examined 240 patients with myocardial infarction with concomitant risk factors. The study found that the inclusion in the standard therapy of beta-blocker carvedilol in individually selected dose and depending on the risk factor of cardiovascular events helps increase myocardial functional reserves and increasing tolerance to physical exertion.


Crystal structure of the vitamin B12 biosynthetic cobaltochelatase, CbiXS, from Archaeoglobus fulgidus.
The Archaeoglobus fulgidus gene af0721 encodes CbiX(S), a small cobaltochelatase associated with the anaerobic biosynthesis of vitamin B12 (cobalamin). The protein was shown to have activity both in vivo and in vitro, catalyzing the insertion of Co2+ into sirohydrochlorin. The structure of CbiX(S) was determined in two different crystal forms and was shown to consist of a central mixed beta-sheet flanked by four alpha-helices, one of which originates in the C-terminus of a neighboring molecule. CbiX(S) is about half the size of other Class II tetrapyrrole chelatases. The overall topography of CbiX(S) exhibits substantial resemblance to both the N- and C-terminal regions of several members of the Class II metal chelatases involved in tetrapyrrole biosynthesis. Two histidines (His10 and His74), are in similar positions as the catalytic histidine residues in the anaerobic cobaltochelatase CbiK (His145 and His207). In light of the hypothesis that suggests the larger chelatases evolved via gene duplication and fusion from a CbiX(S)-like enzyme, the structure of AF0721 may represent that of an "ancestral" precursor of class II metal chelatases.


American Society of Clinical Oncology guidelines for the use of hematopoietic colony-stimulating factors.
The hematopoietic colony-stimulating factors have been introduced into clinical practice as additional supportive measures that can reduce the likelihood of neutropenic complications due to chemotherapy. Clinical benefit has been shown, but the high cost of colony-stimulating factors has led to concern about their appropriate use. The American Society of Clinical Oncology has established evidence-based, clinical practice guidelines for the use of colony-stimulating factors in patients who are not enrolled in clinical trials. An expert multidisciplinary panel reviewed the clinical data documenting the activity of colony-stimulating factors. For each common clinical situation, the panel formulated a guideline to encourage reasonable use of colony-stimulating factors to preserve effectiveness but discourage excess use when little marginal benefit is anticipated. Outcomes considered in evaluating colony stimulating factor benefit included duration of neutropenia, incidence of febrile neutropenia, incidence and duration of antibiotic use, frequency and duration of hospitalization, infectious mortality, chemotherapy dose intensity, chemotherapy efficacy, quality of life, colony-stimulating factor toxicity, and economic impact. To the extent that these data were available, the panel placed greatest value on survival benefit, reduction in rates of febrile neutropenia, decreased hospitalization, and reduced costs. Lesser value was placed on alterations in absolute neutrophil counts.


Anaplasia and grading in medulloblastomas.
The variable clinical outcomes of medulloblastoma patients have prompted a search for markers with which to tailor therapies to individuals. In this review, we discuss clinical, histological and molecular features that can be used in such treatment customization, focusing on how histopathological grading can impact both patient care and research on the molecular basis of CNS embryonal tumors. Medulloblastomas span a histological spectrum ending in overtly malignant large cell/anaplastic lesions characterized by increased nuclear size, marked cytological anaplasia, and increased mitotic and apoptotic rates. These "high-grade" lesions make up approximately one quarter of medulloblastomas, and recur and metastasize more frequently than tumors lacking anaplasia. We believe anaplastic change represents a type of malignant progression common to many medulloblastoma subtypes and to other CNS embryonal lesions as well. Correlation of these histological changes with the accumulation of genetic events suggests a model for the histological and molecular progression of medulloblastoma.


The Reading Signatures of Agreement Attraction.
The comprehension of subject-verb agreement shows "attraction effects," which reveal that number computations can be derailed by nouns that are grammatically unlicensed to control agreement with a verb. However, previous results are mixed regarding whether attraction affects the processing of grammatical and ungrammatical sentences alike. In a large-sample eye-tracking replication of Lago et al. (2015), we support this "grammaticality asymmetry" by showing that the reading profiles associated with attraction depend on sentence grammaticality. In ungrammatical sentences, attraction affected both fixation durations and regressive eye-movements at the critical disagreeing verb. Meanwhile, both grammatical and ungrammatical sentences showed effects of the attractor noun number prior to the verb, in the first- and second-pass reading of the subject phrase. This contrast suggests that attraction effects in comprehension have at least two different sources: the first reflects verb-triggered processes that operate mainly in ungrammatical sentences. The second source reflects difficulties in the encoding of the subject phrase, which disturb comprehension in both grammatical and ungrammatical sentences.


Recognising air embolism as a complication of vascular access.
The insertion and maintenance of advanced vascular access devices is increasingly becoming the remit of advanced nurses. Understanding the potential for air embolism as a complication of this procedure, recognising and managing the signs and symptoms, and being able to apply preventative measures, are imperative to enhance patient safety. A range of outcomes can present from air embolism depending on the rate and volume of air entrained, from sub-clinical to death, so the application of expert knowledge and vigilance is essential to minimise risk. According the the available literature, supplemental oxygen administration appears to be the most effective treatment.


Discovery of a (19)F MRI sensitive salinomycin derivative with high cytotoxicity towards cancer cells.
Salinomycin is a promising anti-cancer agent which selectively targets cancer stem cells. To improve its potency and selectivity, an analog library of salinomycin was generated by site-specific modification and CuAAc derivatization. Through a cytotoxicity analysis of the library, a fluorinated analog with high potency, selectivity, and (19)F MRI sensitivity was discovered as a novel theranostic agent.


Clinical utility of patiromer, sodium zirconium cyclosilicate, and sodium polystyrene sulfonate for the treatment of hyperkalemia: an evidence-based review.
Hyperkalemia is a serious medical condition that often manifests in patients with chronic kidney disease and heart failure. Renin-angiotensin-aldosterone system inhibitors are known to improve outcomes in these disease states but can also cause drug-induced hyperkalemia. New therapeutic options exist for managing hyperkalemia in these patients which warrant evidence-based evaluation. The objective of this article was to review the efficacy and safety evidence for patiromer, sodium zirconium cyclosilicate (ZS9), and sodium polystyrene sulfonate (SPS) for the treatment of hyperkalemia. Current treatment options to enhance potassium excretion are SPS and loop diuretics, which are complicated by ambiguous efficacy and known toxicities. Patiromer and ZS9 are new agents designed to address this treatment gap. Both unabsorbable compounds bind potassium in the gastrointestinal (GI) tract to facilitate fecal excretion. The capacity to bind other medications in the GI tract infers high drug-drug interaction potential, which has been demonstrated with patiromer but not yet investigated with ZS9 or SPS. Phase II and III clinical trials of patiromer and ZS9 demonstrated clear evidence of a dose-dependent potassium-lowering effect and the ability to initiate, maintain, or titrate renin-angiotensin-aldosterone system inhibitors. There is limited evidence base for SPS: two small clinical trials indicated potassium reduction in chronic hyperkalemia. All agents may cause adverse GI effects, although they are less frequent with ZS9. Concerns remain for SPS to cause rare GI damage. Electrolyte abnormalities occurred with patiromer and SPS, whereas urinary tract infections, edema, and corrected QT-interval prolongations were reported with ZS9. Patiromer and ZS9 have improved upon the age-old standard SPS for the treatment of hyperkalemia. Additional research should focus on drug-drug interactions in patients on multiple medications, incidence of rare adverse events, and use in high-risk populations.


Screening Estrogen Receptor Modulators in a Paper-Based Breast Cancer Model.
The health risks associated with acute and prolonged exposure to estrogen receptor (ER) modulators has led to a concerted effort to identify and prioritize potential disruptors present in the environment. ER agonists and antagonists are identified with end-point assays, quantifying changes in cellular proliferation or gene transactivation in monolayers of estrogen receptor alpha expressing (ER+) cells upon exposure. While these monolayer cultures can be prepared, dosed, and analyzed in a highly parallelized manner, they are unable to predict the potencies of ER modulators in vivo accurately. Physiologically relevant model systems that better predict tissue- or organ-level responses are needed. To address this need, we describe here a screening platform capable of quantitatively assessing ER modulators in 96 chemically isolated 3D cultures. These cultures are supported in wax-patterned paper scaffolds whose design has improved performance and throughput over previously described paper-based setups. To highlight the potential of paper-based cultures for toxicity screens, we measured the potency of known ER modulators with a luciferase-based reporter assay. We also quantified the proliferation and invasion of two ER+ cell lines in the presence of estradiol. Despite the inability of the current setup to better predict in vivo potencies of ER modulators than monolayer cultures, the results demonstrate the potential of this platform to support increasingly complex and physiologically relevant tissue-like structures for environmental chemical risk assessment.


Phosphorylation of fibrinogen by casein kinase 2.
Casein kinase 2 from rat liver cytosol phosphorylated human fibrinogen in a reaction that was not stimulated by Ca2+ or cyclic AMP, but was markedly inhibited by heparin, and proceeded at a similar rate when either ATP or GTP was used as phosphate donor. Analysis of casein kinase 2 by glycerol-density-gradient centrifugation showed that the activities towards fibrinogen, casein, phosvitin, high-mobility-group protein 14 and glycogen synthase coincided. Maximal incorporation into fibrinogen by casein kinase 2 averaged 1 mol of phosphate/mol of protein substrate, most of it in the alpha-chain, although some phosphorylation of the beta-chain was also detected. Analysis of phosphorylated alpha-chain revealed that most of the phosphate was incorporated on serine. Phosphorylation of human fibrinogen was also performed by casein kinase 2 from human polymorphonuclear leucocytes, lymphocytes and platelets.


The role of toll-like receptor 2 in the recognition of Aggregatibacter actinomycetemcomitans.
Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) is a Gram-negative bacterium present in the oral cavity and is usually associated with localized aggressive periodontitis. Isolated antigens from A. actinomycetemcomitans can activate innate immune cells through Toll-like receptors (TLRs), which are molecules that recognize structural components conserved among microorganisms. In this study, we evaluate the role of TLR2 in the recognition of A. actinomycetemcomitans. Macrophages and neutrophils from knockout mice with targeted disruption of TLR2 (TLR2(-/-) mice) and wild-type mice were collected and used for the subsequent assays. The production of cytokines and chemokines was evaluated by enzyme-linked immunosorbent assay (ELISA), and the presence of apoptotic cells was determined by flow cytometry. In addition, the mechanisms that modulate the outcome of A. actinomycetemcomitans-induced periodontal disease in TLR2(-/-) mice were examined. The results show that TLR2-deficient mice developed more severe periodontitis after A. actinomycetemcomitans infection, characterized by significantly higher bone loss and inflammatory cell migration to periodontal tissues. The inflammatory cell influx into the peritoneal cavities of TLR2(-/-) mice was three-fold lower than that observed for the littermate controls. A significantly diminished production of the cytokines tumor necrosis factor-alpha and interleukin-1beta as well as the chemokine CC-ligand-5 in the peritoneal cavities of TLR2(-/-) mice was observed. In addition, a high frequency of apoptotic cells in the inflammatory exudates from TLR2(-/-) mice was observed. Phagocytosis and nitric oxide production was diminished in cells from TLR2(-/-) mice, facilitating the dissemination of the pathogen to the spleen. The results of this study highlight the involvement of TLR2 in recognizing A. actinomycetemcomitans and its essential role in controlling A. actinomycetemcomitans infection.


Interferon gamma and granulocyte/macrophage colony-stimulating factor inhibit growth and induce antigens characteristic of myeloid differentiation in small-cell lung cancer cell lines.
The expression of several macrophage and hemopoietic cell surface markers recently described on small-cell lung cancer (SCLC) cell lines was studied by use of flow cytometry. The antigens Leu-M3, Leu-7, and HLA-DR were examined for their modulation by human interferon gamma and granulocyte/macrophage colony-stimulating factor (GM-CSF). Both of these lymphokines generally induced enhanced expression of hemopoietic markers in several SCLC lines. A differential response to these two hormones was observed, in that qualitative and quantitative differences in marker modulation among the tested cell lines were apparent. In addition to regulating the antigenic phenotype of these cells, both interferon gamma and GM-CSF had antiproliferative effects on SCLC lines as determined by [3H]thymidine incorporation and clonal growth in agar. These results suggest that interferon gamma and GM-CSF promote a differentiation process in SCLC cell lines that has characteristics in common with myeloid differentiation. These findings support the theory that SCLC tumors are hemopoietic cells that arise from macrophages or their precursors and suggest new therapeutic modalities for the treatment of lung cancer.


OCT4/POU5F1 is indispensable for the lineage differentiation of the inner cell mass in bovine embryos.
The mammalian blastocyst undergoes two lineage segregations, that is, formation of the trophectoderm and subsequently differentiation of the hypoblast (HB) from the inner cell mass, leaving the epiblast (EPI) as the remaining pluripotent lineage. To clarify the expression patterns of markers specific for these lineages in bovine embryos, we analyzed day 7, 9, and 12 blastocysts completely produced in vivo by staining for OCT4, NANOG, SOX2 (EPI), and GATA6, SOX17 (HB) and identified genes specific for these developmental stages in a global transcriptomics approach. To study the role of OCT4, we generated OCT4-deficient (OCT4 KO) embryos via somatic cell nuclear transfer or in vitro fertilization. OCT4 KO embryos reached the expanded blastocyst stage by day 8 but lost NANOG and SOX17 expression, while SOX2 and GATA6 were unaffected. Blastocysts transferred to recipient cows from day 6 to 9 expanded, but the OCT4 KO phenotype was not rescued by the uterine environment. Exposure of OCT4 KO embryos to exogenous FGF4 or chimeric complementation with OCT4 intact embryos did not restore NANOG or SOX17 in OCT4-deficient cells. Our data show that OCT4 is required cell autonomously for the maintenance of pluripotency of the EPI and differentiation of the HB in bovine embryos.


Mitochondrial lactate dehydrogenase is involved in oxidative-energy metabolism in human astrocytoma cells (CCF-STTG1).
Lactate has long been regarded as an end product of anaerobic energy production and its fate in cerebral metabolism has not been precisely delineated. In this report, we demonstrate, for the first time, the ability of a human astrocytic cell line (CCF-STTG1) to consume lactate and to generate ATP via oxidative phosphorylation. (13)C-NMR and HPLC analyses aided in the identification of tricarboxylic acid (TCA) cyle metabolites and ATP in the astrocytic mitochondria incubated with lactate. Oxamate, an inhibitor of lactate dehydrogenase (LDH), abolished mitochondrial lactate consumption. Electrophoretic and fluorescence microscopic analyses helped localize LDH in the mitochondria. Taken together, this study implicates lactate as an important contributor to ATP metabolism in the brain, a finding that may significantly change our notion of how this important organ manipulates its energy budget.


Effect of two preclinical curricula on NBME Part I examination performance.
The Michigan State University College of Human Medicine conducts two preclinical medical education programs. In Track I (lecture-based), students attend classes 24 hours per week, and lecture time totals 908 hours over a 50-week period. In Track II (problem-based), students attend classes only 12 hours per week, and lecture time totals 112 hours over the same 50-week period. Institution of the Part I examination of the National Board of Medical Examiners (NBME) as a graduation requirement provided an opportunity to compare the performances of students in both tracks. When students from each track with similar Science Problems subtest scores on the Medical College Admission Test were compared, no significant differences were observed in the students' total scores or pass rate on the NBME examination. However, there were significant differences in scores on the microbiology subtest of the NBME examination, with the Track I students achieving higher scores. The 1984 report of the Project Panel on the General Professional Education of the Physician and College Preparation for Medicine of the Association of American Medical Colleges stressed the need to examine critically and consider reducing the scheduled instructional and lecture hours in preclinical medical education programs. In the study reported here, the authors demonstrated that reduction of scheduled instructional time, when replaced by a guided problem-solving program, is not detrimental to students' performance on the NBME Part I examination.


Serum neopterin levels in lung and breast cancer patients undergoing radiotherapy and/or chemotherapy.
The elevated neopterin levels observed in numerous haemotological diseases and parenchymatous malignomas suggested neopterin might be useful as a tumor marker. In a group of 60 patients suffering from advanced lung (18) or breast (42) cancer, serial determinations of serum neopterin were made before, during and after radiation and/or chemotherapy, during an observation period of 18 months, to check the potential value of neopterin in the therapeutic management of these tumor types. The neopterin profiles were compared with the clinical course and analysed with regard to response to therapy. Numbers of pathologically elevated serum neopterin levels were low. In only few cases was any agreement detected between changes in neopterin levels and therapeutic effects. Even chemotherapeutically induced depression in white blood counts generally did not increase serum neopterin levels. Thus the clinical suitability of neopterin as an adjuvant parameter in assessing therapeutic effects in lung or breast cancer could not be documented.


Food-Dependent Plasticity in Caenorhabditis elegans Stress-Induced Sleep Is Mediated by TOR-FOXA and TGF-β Signaling.
Behavioral plasticity allows for context-dependent prioritization of competing drives, such as sleep and foraging. Despite the identification of neuropeptides and hormones implicated in dual control of sleep drive and appetite, our understanding of the mechanism underlying the conserved sleep-suppressing effect of food deprivation is limited. Caenorhabditis elegans provides an intriguing model for the dissection of sleep function and regulation as these nematodes engage a quiescence program following exposure to noxious conditions, a phenomenon known as stress-induced sleep (SIS). Here we show that food deprivation potently suppresses SIS, an effect enhanced at high population density. We present evidence that food deprivation reduces the need to sleep, protecting against the lethality associated with defective SIS. Additionally, we find that SIS is regulated by both target of rapamycin and transforming growth factor-β nutrient signaling pathways, thus identifying mechanisms coordinating sleep drive with internal and external indicators of food availability.


Renewable Sources of Plant Biostimulation: Microalgae as a Sustainable Means to Improve Crop Performance.
Plant biostimulants (PBs) attract interest in modern agriculture as a tool to enhance crop performance, resilience to environmental stress, and nutrient use efficiency. PBs encompass diverse organic and inorganic substances (humic acids and protein hydrolysates) as well as prokaryotes (e.g., plant growth promoting bacteria) and eukaryotes such as mycorrhiza and macroalgae (seaweed). Microalgae, which comprise eukaryotic and prokaryotic cyanobacteria (blue-green algae), are attracting growing interest from scientists, extension specialists, private industry and plant growers because of their versatile nature: simple unicellular structure, high photosynthetic efficiency, ability for heterotrophic growth, adaptability to domestic and industrial wastewater, amenability to metabolic engineering, and possibility to yield valuable co-products. On the other hand, large-scale biomass production and harvesting still represent a bottleneck for some applications. Although it is long known that microalgae produce several complex macromolecules that are active on higher plants, their targeted applications in crop science is still in its infancy. This paper presents an overview of the main extraction methods from microalgae, their bioactive compounds, and application methods in agriculture. Mechanisms of biostimulation that influence plant performance, physiology, resilience to abiotic stress as well as the plant microbiome are also outlined. Considering current state-of-the-art, perspectives for future research on microalgae-based biostimulants are discussed, ranging from the development of crop-tailored, highly effective products to their application for increasing sustainability in agriculture.


ICU team composition and its association with ABCDE implementation in a quality collaborative.
Awakening, Breathing Coordination, Delirium, and Early Mobility bundle (ABCDE) should involve an interprofessional team, yet no studies describe what team composition supports implementation. We administered a survey at MHA Keystone Center ICU 2015 workshop. We measured team composition by the frequency of nurse, respiratory therapist, physician, physical therapist, nurse practitioner/physician assistant or nursing assistant involvement in 1) spontaneous awakening trials (SATs), 2) spontaneous breathing trials, 3) delirium and 4) early mobility. We assessed ABCDE implementation using a 5-point Likert ("routine part of every patient's care" - "no plans to implement"). We used ordinal logistic regression to examine team composition and ABCDE implementation, adjusting for confounders and clustering. From 293 surveys (75% response rate), we found that frequent nurse [OR 6.1 (1.1-34.9)] and physician involvement [OR 4.2 (1.3-13.4)] in SATs, nurse [OR 4.7 (1.6-13.4)] and nursing assistant's involvement [OR 3.9 (1.2-13.5)] in delirium and nurse [OR 2.8 (1.2-6.7)], physician [OR (3.6 (1.2-10.3)], and nursing assistants' involvement [OR 2.3 (1.1-4.8)] in early mobility were significantly associated with higher odds of routine ABCDE implementation. ABCDE implementation was associated with frequent involvement of team members, suggesting a need for role articulation and coordination.


The progressive nature of peripheral arterial disease in young adults: a prospective analysis of white men referred to a vascular surgery service.
The onset of symptomatic peripheral arterial disease at a young age (premature PAD) has been associated with rapid progression, bypass graft failure, and amputation. This study was performed to document the incidence of these complications and to determine the risk factors for poor outcome in patients with premature PAD. This study was designed as a prospective longitudinal analysis, with patients who were ambulatory or hospitalized at a single vascular referral institution. The subjects were 51 white men with onset of PAD symptoms before the age of 45 years (mean age of onset, 41 +/- 0.5 years) and represented consecutive patients who were seen at the vascular surgery service during a 4-year period. Thirty of the study subjects (58%) were recruited during the first 2 years. The main outcome measures were number and type of lower extremity revascularization procedures or amputations that were necessitated during the follow-up period. During a mean follow-up period of 73 +/- 6 months, 15 patients (29%) had PAD that remained stable without interventions and 15 (29%) had PAD that remained stable for a mean of 76 +/- 13 months after a single intervention. Twenty-one patients (41%) required multiple operations or major amputations. In a comparison of the 30 PAD patients whose conditions were stable with or without a single intervention with the 21 PAD patients who required multiple interventions (REDO), there were no differences in smoking, hypertension, diabetes, or dyslipidemias. The REDO group had a younger mean age at the onset of symptoms (39 +/- 1 years vs 43 +/- 2 years; P <.001). At entry, the REDO patients had a higher prevalence of infrainguinal or multilevel disease (57% vs 20%; P =.03), a lower mean ankle brachial index (0. 44 +/- 0.04 vs 0.56 +/- 0.03; P =.02), and more frequent tissue loss (24% vs 0; P =.005). The REDO patients had a higher mean lipoprotein (a) level than did the patients with stable conditions (51 +/- 11 mg/dL vs 27 +/- 5 mg/dL; P =.03), but there were no significant differences in the mean plasma homocysteine levels (19 +/- 2 micromol/L vs 16 +/- 1 micromol/L) or in the proportion of patients with hypercoagulable states (33% vs 30%). The only predictive variables that were selected with stepwise logistic regression analysis were age at onset (P <.002; odds ratio, 1.4; 95% confidence interval, 1.11 to 1.81) and ankle brachial index of less than 0.5 (P <.008; odds ratio, 6.4; 95% confidence interval, 1.5 to 27.3). Although 60% of the white men with premature PAD who were referred to a vascular surgery service had conditions that appeared to remain stable, these data show that approximately 40% of the patients will require multiple interventions because of disease progression or bypass graft failure. Clinical indicators, not serum markers, are predictors of poor outcome in patients with premature PAD. The results of this study suggest that patients with onset of PAD before the age of 43 years who have objective evidence of advanced disease are predisposed to multiple interventions.


Smooth and slipless walking mechanism inspired by the open-close cycle of a beetle claw.
This study investigated the function of the beetle's claw for its smooth and slipless walking and designed an artificial claw open-close cycle mechanism to mimic the beetle's walking. First, the effects of claw opening and closing on beetles' ability to attach to surfaces were examined. A beetle does not have an attachment pad, and only its claws work to grip the ground; its claw opens and closes and attaches with two sharp hooks. With their claws, beetles can smoothly walk, neither slipping on nor having their claws stuck in the surface. How do they perform smooth walking with sharp claws? In this study, we observed that beetles close their claws when they raise and swung their legs forward, while they open their claws when they lowered their legs to the ground. We then conducted non-destructive tests: their claws were forced open or closed. There was a significant difference in the trajectories of forced-closed claws compared to intact claws and forced-open claws. When their claws were forced-closed, this caused slippage in walking. On the other hand, when a claw was forced-open and its rotation was also inhibited, the claw stuck heavily in the surface, and the beetle could not walk. Based on these findings, we designed an artificial claw to open and close in the same cyclic manner as in the case of natural beetles. The performance of the artificial claw was consistent with the conclusions drawn from natural beetles: the locomotive robot with the artificial claw smoothly moved without slippage. Through these observations, non-destructive tests and performance of the bio-inspired artificial claws, this study confirmed the function of the open-close cycle of beetle claws and demonstrated and successfully adopted it for a locomotive robot.


Development and Evaluation of a Proficiency-based and Simulation-based Surgical Skills Training for Technical Medicine Students.
This article was migrated. The article was marked as recommended. Objective Surgical graduate training to achieve practice-ready students is needed, yet is often lacking. This study developed and evaluated a proficiency-based, simulation-based course for basic surgical skills at graduate level. Learning outcomes were measured at the level of knowledge and skills and evaluated with a post-course questionnaire after students' clinical rotations. Methods The surgical skills course was anchored to surgical patient flow and covered topics and skills related to pre-, intra-, and post-operative care, including case-based medical reasoning, patient safety, infection management, operating theatre etiquette, scrubbing and donning, instrument handling, local anaesthesia, excision of tissue, and suturing. Students were assessed on knowledge and procedural skills. Results 155 graduate Technical Medicine students from academic years 2015-2016 and 2016-2017 entered this 10-week, 3 ECTS credits graduate Surgical Skills course. Pass rates of the knowledge test were 78%, and 87% for the procedural skill assessment. Graduate students reached proficiency level in a simulation-based basic surgical skills course. Students stated to go with confidence to the operating room and felt competent in performing four basic surgical skills. Conclusion Based on this study, we recommend that proficiency-based training using simulation should be standard in surgical curricula before students are allowed to practice on patients.


Evaluation of Immediate and Delayed Microleakage of Class V Cavities Restored with Chitosan-incorporated Composite Resins: An In Vitro Study.
To evaluate and compare the microleakage of unmodified microhybrid composite and 0.2% chitosan-incorporated composite in class V cavities restored immediately and after 3 months of storage in artificial saliva. Sixty human permanent maxillary premolars were collected and standardized class V cavity prepared on the buccal surface of each tooth with dimensions: mesiodistally 3 mm, occluso cervically 2 mm, and depth of 1.5 mm and restored with microhybrid composite and chitosan-incorporated composite resins respectively and randomly divided: Group I: control-microhybrid composite (n = 30): (a) 15 teeth tested immediately (b) 15 teeth tested after 3 months. Group II-restored with chitosan + composite (n = 30): (a) 15 teeth tested immediately (b) 15 teeth tested after 3 months. Specimens were stored in artificial saliva following which a dye extraction test was carried out using a spectrophotometer. There was no statistically significant difference in microleakage score between the chitosan-composite group and unmodified composite group when evaluated immediately after placing the restoration. Microleakage values of the unmodified composite group increased significantly after 3 months of storage in artificial saliva and values of the chitosan-composite group did not differ significantly even after 3 months of storage. Microleakage was seen significantly less in the chitosan-composite group compared to the unmodified composite group after 3 months of storage in artificial saliva. It can be concluded that chitosan-incorporated composite seems to have improved mechanical properties and forms a more stable bond when compared with unmodified microhybrid composite in addition to being antibacterial. Considering the advantageous properties of this material, it may be clinically useful in restoring class V cavities in patients with high caries risk. However, further in vitro and in vivo studies need to be carried out. Deb A, Pai V, Nadig RR. Evaluation of Immediate and Delayed Microleakage of Class V Cavities Restored with Chitosan-incorporated Composite Resins: An In Vitro Study. Int J Clin Pediatr Dent 2021;14(5):621-627.


Antisense RNA modulation of alkyl hydroperoxide reductase levels in Helicobacter pylori correlates with organic peroxide toxicity but not infectivity.
Much of the gene content of the human gastric pathogen Helicobacter pylori ( approximately 1.7-Mb genome) is considered essential. This view is based on the completeness of metabolic pathways, infrequency of nutritional auxotrophies, and paucity of pathway redundancies typically found in bacteria with larger genomes. Thus, genetic analysis of gene function is often hampered by lethality. In the absence of controllable promoters, often used to titrate gene function, we investigated the feasibility of an antisense RNA interference strategy. To test the antisense approach, we targeted alkyl hydroperoxide reductase (AhpC), one of the most abundant proteins expressed by H. pylori and one whose function is essential for both in vitro growth and gastric colonization. Here, we show that antisense ahpC (as-ahpC) RNA expression from shuttle vector pDH37::as-ahpC achieved an approximately 72% knockdown of AhpC protein levels, which correlated with increased susceptibilities to hydrogen peroxide, cumene, and tert-butyl hydroperoxides but not with growth efficiency. Compensatory increases in catalase levels were not observed in the knockdowns. Expression of single-copy antisense constructs (expressed under the urease promoter and containing an fd phage terminator) from the rdxA locus of mouse-colonizing strain X47 achieved a 32% knockdown of AhpC protein levels (relative to wild-type X47 levels), which correlated with increased susceptibility to organic peroxides but not with mouse colonization efficiency. Our studies indicate that high levels of AhpC are not required for in vitro growth or for primary gastric colonization. Perhaps AhpC, like catalase, assumes a greater role in combating exogenous peroxides arising from lifelong chronic inflammation. These studies also demonstrate the utility of antisense RNA interference in the evaluation of gene function in H. pylori.


Neuronal origins of choice variability in economic decisions.
To investigate the mechanisms through which economic decisions are formed, I examined the activity of neurons in the orbitofrontal cortex while monkeys chose between different juice types. Different classes of cells encoded the value of individual offers (offer value), the value of the chosen option (chosen value), or the identity of the chosen juice (chosen juice). Choice variability was partly explained by the tendency to repeat choices (choice hysteresis). Surprisingly, near-indifference decisions did not reflect fluctuations in the activity of offer value cells. In contrast, near-indifference decisions correlated with fluctuations in the preoffer activity of chosen juice cells. After the offer, the activity of chosen juice cells reflected the decision difficulty but did not resemble a race-to-threshold. Finally, chosen value cells presented an "activity overshooting" closely related to the decision difficulty and possibly due to fluctuations in the relative value of the juices. This overshooting was independent of choice hysteresis.


Standardized Assessment of Resistance Training-Induced Subjective Symptoms and Objective Signs of Immunological Stress Responses in Young Athletes.
From a health and performance-related perspective, it is crucial to evaluate subjective symptoms and objective signs of acute training-induced immunological responses in young athletes. The limited number of available studies focused on immunological adaptations following aerobic training. Hardly any studies have been conducted on resistance-training induced stress responses. Therefore, the aim of this observational study was to investigate subjective symptoms and objective signs of immunological stress responses following resistance training in young athletes. Fourteen (7 females and 7 males) track and field athletes with a mean age of 16.4 years and without any symptoms of upper or lower respiratory tract infections participated in this study. Over a period of 7 days, subjective symptoms using the Acute Recovery and Stress Scale (ARSS) and objective signs of immunological responses using capillary blood markers were taken each morning and after the last training session. Differences between morning and evening sessions and associations between subjective and objective parameters were analyzed using generalized estimating equations (GEE). In post hoc analyses, daily change-scores of the ARSS dimensions were compared between participants and revealed specific changes in objective capillary blood samples. In the GEE models, recovery (ARSS) was characterized by a significant decrease while stress (ARSS) showed a significant increase between morning and evening-training sessions. A concomitant increase in white blood cell count (WBC), granulocytes (GRAN) and percentage shares of granulocytes (GRAN%) was found between morning and evening sessions. Of note, percentage shares of lymphocytes (LYM%) showed a significant decrease. Furthermore, using multivariate regression analyses, we identified that recovery was significantly associated with LYM%, while stress was significantly associated with WBC and GRAN%. Post hoc analyses revealed significantly larger increases in participants' stress dimensions who showed increases in GRAN%. For recovery, significantly larger decreases were found in participants with decreases in LYM% during recovery. More specifically, daily change-scores of the recovery and stress dimensions of the ARSS were associated with specific changes in objective immunological markers (GRAN%, LYM%) between morning and evening-training sessions. Our results indicate that changes of subjective symptoms of recovery and stress dimensions using the ARSS were associated with specific changes in objectively measured immunological markers.


Mechanisms for the inhibition of DNA methyltransferases by tea catechins and bioflavonoids.
In the present investigation, we studied the modulating effects of several tea catechins and bioflavonoids on DNA methylation catalyzed by prokaryotic SssI DNA methyltransferase (DNMT) and human DNMT1. We found that each of the tea polyphenols [catechin, epicatechin, and (-)-epigallocatechin-3-O-gallate (EGCG)] and bioflavonoids (quercetin, fisetin, and myricetin) inhibited SssI DNMT- and DNMT1-mediated DNA methylation in a concentration-dependent manner. The IC(50) values for catechin, epicatechin, and various flavonoids ranged from 1.0 to 8.4 microM, but EGCG was a more potent inhibitor, with IC(50) values ranging from 0.21 to 0.47 microM. When epicatechin was used as a model inhibitor, kinetic analyses showed that this catechol-containing dietary polyphenol inhibited enzymatic DNA methylation in vitro largely by increasing the formation of S-adenosyl-L-homocysteine (a potent noncompetitive inhibitor of DNMTs) during the catechol-O-methyltransferase-mediated O-methylation of this dietary catechol. In comparison, the strong inhibitory effect of EGCG on DNMT-mediated DNA methylation was independent of its own methylation and was largely due to its direct inhibition of the DNMTs. This inhibition is strongly enhanced by Mg(2+). Computational modeling studies showed that the gallic acid moiety of EGCG plays a crucial role in its high-affinity, direct inhibitory interaction with the catalytic site of the human DNMT1, and its binding with the enzyme is stabilized by Mg(2+). The modeling data on the precise molecular mode of EGCG's inhibitory interaction with human DNMT1 agrees perfectly with our experimental finding.


Clinical trials in minimal change disease.
Minimal change disease (MCD) is a pathological condition characterized by subtle glomerular lesions causing massive and reversible proteinuria that is usually steroid sensitive. Recurrence of symptoms of active disease following successful treatment (including proteinuria, oedema and oliguria) and steroid toxicity requires the use of other drugs to attain or maintain remission. Unresolved MCD is considered the initial step in the pathological pathway leading to focal and segmental glomerulosclerosis (FSGS). Historically, cyclophosphamide, chlorambucil, mycophenolate and calcineurin inhibitors have been utilized with success in MCD; however, the chronic nature of the disease and the toxicity of long-term use of these medications has pushed the development of new therapies. Synthetic corticotropin (adrenocorticotropic hormone) and anti-CD20 monoclonal antibodies, for example, are currently under investigation in clinical trials. In addition, these new interventions have dramatically impacted our understanding of the mechanisms of the disease. Phase II-IV clinical trials targeting new mechanisms and/or molecules are in progress. The list is long and includes drugs blocking the adaptive immune system (abatacept and anti-CD40 antibodies), as well as retinoids and the sialic acid precursor N-acetyl-D-mannosamine (ManNAc), two agents that affect the sieving properties of the glomerular basement membrane. Other drugs are being tested against FSGS and, if successful, could also be utilized against MCD. Clinical trials currently in progress should furnish a proper solution to what appears to be a solvable problem.


The high-mobility-group domain of Sox proteins interacts with DNA-binding domains of many transcription factors.
Sox proteins are widely believed to team up with other transcription factors as partner proteins to perform their many essential functions during development. In this study, yeast two-hybrid screens identified transcription factors as a major group of interacting proteins for Sox8 and Sox10. Interacting transcription factors were very similar for these two group E Sox proteins and included proteins with different types of DNA-binding domains, such as homeodomain proteins, zinc finger proteins, basic helix-loop-helix and leucine zipper proteins. In all cases analyzed, the interaction involved the DNA-binding domain of the transcription factor which directly contacted the C-terminal part of the high-mobility-group (HMG) domain. In particular, the C-terminal tail region behind helix 3 of the HMG domain was shown by mutagenesis to be essential for interaction and transcription factor recruitment. The HMG domain thus not only possesses DNA-binding and DNA-bending but also protein-interacting ability which may be equally important for the architectural function of Sox proteins on their target gene promoters.


The carbohydrate components of hydrolysates of gastric secretion and extracts from mucous glands of the gastric body mucosa and antrum.
1. The sugars and amino sugars of hydrolysates of gastric secretion were determined by gas-liquid chromatography. 2. All the gastric aspirations examined showed on hydrolysis the presence of fucose, galactose, mannose, glucose, galactosamine, glucosamine, N-acetylneuraminic acid and sulphate. 3. Galactose and glucosamine were always found in equimolar amounts, but the galactose/galactosamine ratio in different aspirations was 2:1, 3:1, 4:1 or 5:1. Repeated gastric aspirations of each subject examined showed constant ratios of these carbohydrate components. 4. Fucose and sialic acid appear to be related to glucosamine and galactosamine respectively. 5. The carbohydrate components of extracts from the mucous glands of the body mucosa and antrum did not differ from those of gastric secretion.


A recA gene phylogenetic analysis confirms the close proximity of Frankia to Acidothermus.
The closer proximity of Frankia and Acidothermus cellulolyticus relative to the morphologically close Geodermatophilus found previously was confirmed by resequencing the rrs gene of Acidothermus cellulolyticus and the housekeeping gene, recA. The diagnostic sugar 2-O-methyl-D-mannose was detected only in Frankia, while hopanoid lipids were present at high levels in both Acidothermus and Frankia.


The lung may play a role in the pathogenesis of rheumatoid arthritis.
Multiple studies have identified strong associations between the lung and rheumatoid arthritis (RA). Such studies identify a high prevalence of lung disease, both airways and parenchymal disease, in subjects with clinically classifiable RA. It has been suggested that lung disease in RA results from targeting of the lung from circulating autoimmunity or other factors such as medications. However, findings that lung disease, specifically inflammatory airways disease, and lung generation of autoimmunity can be present before the onset of joint symptoms suggest that immune reactions in the lung may be involved in the initial development of RA-related autoimmunity. Herein we review these issues in detail, as well as outline a potential research agenda to understand the natural history of lung involvement in RA and its relation to the overall pathogenesis of RA.


Changing trends in vancomycin-resistant enterococci in French hospitals, 2001-08.
Unprecedented outbreaks of vancomycin-resistant enterococci (VRE) have occurred in French hospitals since 2004. The aim of this study was to provide a picture of the spread and control of VRE in France and to characterize the isolates. Notification of VRE cases to Institut de Veille Sanitaire has been mandatory since 2001. Isolates of VRE were sent to the National Reference Centre for species and vancomycin-resistance gene identification. Isolates were tested for antimicrobial susceptibility and typed by PFGE and multilocus sequence typing. Five hundred and four VRE notifications from 195 hospitals were recorded, corresponding to 2475 cases of infection (n=243) or colonization (n=2232) and 74 episodes of clustered cases. Outbreaks were controlled by implementation of infection control measures, although the number of new hospitals reporting isolation of VRE was increasing. The majority of 902 VRE isolated from 2006 to 2008 were Enterococcus faecium (94.8%) with the vanA or vanB gene. No isolate was resistant to linezolid, tigecycline or fusidic acid. PFGE analysis showed 161 different patterns. Generally a few predominant clones and several minor clones spread in a single hospital. In a subset of 46 representatives of PFGE clones, 13 different sequence types were characterized, all belonging to clonal complex CC17, while the esp and hyl genes were inconsistently detected. The national mandatory notification of unusual nosocomial events allowed rapid identification of VRE outbreaks and early implementation of control measures that have proved effective. However, VRE continue to emerge in a growing number of hospitals.


Childhood exposure to infection and risk of adult onset wheeze and atopy.
The prevalence of asthma and allergic diseases in children and young adults is inversely associated with family size. It has been suggested that more frequent exposure to infections in a large family group, particularly those spread by the faecal-oral route, may protect against atopic diseases, although not all published data support this hypothesis. Whether similar considerations apply to adult onset wheeze is unknown. The relationship between adult onset wheezing and atopy measured in adulthood and childhood exposure to a range of infections was investigated. A nested case control study of participants in a 30 year follow up survey was conducted. Questionnaire data on childhood infections had been obtained in a 1964 survey. In 1995 a further questionnaire on respiratory symptoms and other risk factors for wheezing illness was administered, total IgE, skin and RAST tests were performed, and serum was stored. In 1999 serological tests for hepatitis A, Helicobacter pylori, and Toxoplasma gondii were performed on the stored samples. Information from the 1964 questionnaires was available for 97 cases and 208 controls and serological tests were obtained for 85 cases and 190 controls. The potential risk factors were examined for all cases, those who reported doctor diagnosed asthma, those who described persistent cough and phlegm with wheeze, and subjects stratified by atopic status. The sibship structure was similar in cases and controls. In univariate analysis of all cases, childhood infections reported by parents as acquired either before or after the age of three years did not influence case:control or atopic status. Seropositivity was also similar for all cases and controls, but cases in the subgroup with chronic cough and phlegm were more likely to be seropositive for hepatitis A and H pylori. Seropositivity was unrelated to atopic status. In multivariate analyses both the effect of having two or more younger siblings (OR 0.1, 95% CI 0.03 to 0.8) and of acquiring measles up to the age of three (OR 0.2, CI 0.03 to 0.8) were significantly related to a lower risk of doctor diagnosed asthma. In these well characterised subjects, exposure to infections as measured by parental reports obtained at age 10-14 years and by serological tests obtained in adulthood did not influence the development of wheezing symptoms or atopic status in adulthood. However, early exposure to measles and family size may be associated with a lower risk of adult onset doctor diagnosed asthma.


The baboon: A model for the study of language evolution.
Comparative research on the origins of human language often focuses on a limited number of language-related cognitive functions or anatomical structures that are compared across species. The underlying assumption of this approach is that a single or a limited number of factors may crucially explain how language appeared in the human lineage. Another potentially fruitful approach is to consider human language as the result of a (unique) assemblage of multiple cognitive and anatomical components, some of which are present in other species. This paper is a first step in that direction. It focuses on the baboon, a non-human primate that has been studied extensively for years, including several brain, anatomical, cognitive and cultural dimensions that are involved in human language. This paper presents recent data collected on baboons regarding (1) a selection of domain-general cognitive functions that are core functions for language, (2) vocal production, (3) gestural production and cerebral lateralization, and (4) cumulative culture. In all these domains, it shows that the baboons share with humans many cognitive or brain mechanisms which are central for language. Because of the multidimensionality of the knowledge accumulated on the baboon, that species is an excellent nonhuman primate model for the study of the evolutionary origins of language.


The phenotype of mixed connective tissue disease patients having associated interstitial lung disease.
We aimed to compare two matched populations of patients with MTCD with and without associated ILD and to identify predictive factors for ILD progression and severity. This international multicenter retrospective study (14 tertiary hospitals), included MCTD patients who fulfilled at least one historical MCTD classification criteria. ILD was defined by the presence of typical chest high-resolution computed tomography (HRCT) abnormalities. Factors associated with ILD were assessed at baseline. Long-term progressive ILD was assessed in MCTD-ILD patients with multiple forced vital capacity (FVC) measurements. 300 patients with MCTD were included. Mean age at diagnosis was 39.7 ± 15.4 years and 191 (63.7%) were women. Mean follow-up was 7.8 ± 5.5 years. At baseline, we identified several factors associated with ILD presence: older age (p = 0.01), skin thickening (p = 0.03), upper gastro-intestinal (GI) symptoms (p<0.001), FVC <80% (p<0.0001), diffusing capacity for carbon monoxide <80% (p<0.0001), anti-topoisomerase antibodies (p = 0.01), SSA/Ro antibodies (p = 0.02), cryoglobulinemia (p = 0.04) and elevated C-reactive protein (p<0.001). Patients with MTCD-ILD were more likely to be treated with synthetic immunosuppressant agents (p<0.001) in particular mycophenolate mofetil (p = 0.03). Digital ulcers (DU) were identified as a risk factor for FVC decline >10%. During follow-up mortality was higher in the MTCD-ILD group (p<0.001). In this large international cohort of patients with MTCD, we identified different factors associated with ILD. Our findings also provide evidence that MCTD-ILD patients have increased mortality and that DU are associated with progressive lung disease.