Nanoscale Elastoplastic Wrinkling of Ultrathin Molecular Films.
Ultrathin molecular films deposited on a substrate are ubiquitously used in electronics, photonics, and additive manufacturing methods. The nanoscale surface instability of these systems under uniaxial compression is investigated here by molecular dynamics simulations. We focus on deviations from the homogeneous macroscopic behavior due to the discrete, disordered nature of the deformed system, which might have critical importance for applications. The instability, which develops in the elastoplastic regime above a finite critical strain, leads to the growth of unidimensional wrinkling up to strains as large as 0.5. We highlight both the dominant wavelength and the amplitude of the wavy structure. The wavelength is found to scale geometrically with the film length, λ∝L, up to a compressive strain of ε≃0.4 at least, depending on the film length. The onset and growth of the wrinkling under small compression are quite well described by an extended version of the familiar square-root law in the strain ε observed in macroscopic systems. Under large compression (ε≳0.25), we find that the wrinkling amplitude increases while leaving the cross section nearly constant, offering a novel interpretation of the instability with a large amplitude. The contour length of the film topography is not constant under compression, which is in disagreement with the simple accordion model. These findings might be highly relevant for the design of novel and effective wrinkling and buckling patterns and architectures in flexible platforms for electronics and photonics.


Ethics and cross-cultural nursing.
This article examines how cultural misunderstandings and language differences generate ethical dilemmas in cross-cultural nursing. It explores the consequences of actions that result when health care providers lack an awareness of the value systems of patients that differ from their own. Described are the principles arising from ethical theory, their application to nursing, and incorporation into professional codes of ethics. Two case studies illustrate the close relationship between culture, health, and communication, with language barriers a significant factor in predicting the outcomes of care. Recommendations are offered for cultural competency training for health care institutions, nursing administrators, and nursing educators.


Hypertonic saline dextran alleviates hepatic injury in hypovolemic rats undergoing porta hepatis occlusion.
To monitor the ischemic and/or reperfusion injury after porta hepatis occlusion (Pringle maneuver) in livers subjected to hypotension, serum alanine amino transferase (ALT), liver malondialdehyde (MDA), and liver glutathione (GSH) levels were measured. MDA is a by-product of oxidant-induced lipid peroxidation, and GSH is an endogenous antioxidant. The effects of lactated Ringer's (LR) and hypertonic saline (7.5%)/Dextran (6%; HSD) resuscitation on liver injury, if any, was investigated. Rats in sham (S, n = 8) and five other groups (n = 8) underwent femoral artery and vein catheterization and laparotomy. The hemorrhage and ischemia (HI) group was bled 30% of their blood volume and had their porta hepatis occluded for 30 min. The HI, LR, and HSD groups underwent both hemorrhage and occlusion. Thirty minutes after hemorrhage, the LR and HSD groups received either LR (equivalent to three times the shed blood) or HSD (10 mL/kg) resuscitation over 30 min. Both LR and HSD resuscitation lowered the increased ALT and liver tissue MDA seen in the HI group. ALT was decreased from 348 +/- 93 IU/L in the HI group to 200 +/- 98 IU/L in the LR and 139 +/- 74 IU/L in the HSD groups. Liver tissue MDA was 353 +/- 22 nmol/g/tissue in the HI group and LR decreased it to 261 +/- 17 nmol/g/tissue, whereas HSD decreased it to 273 +/- 20 nmol/g/tissue. The decrease in ALT and the increase in liver GSH were more pronounced with HSD resuscitation (P < 0.05). HSD seems to be more effective than LR in decreasing the liver tissue damage produced by total hepatic inflow occlusion under hypovolemic conditions.


Up-regulation of the KLF2 transcription factor by fluid shear stress requires nucleolin.
We have previously characterized the regulation of the KLF2 transcription factor gene by describing an induction complex that binds to and regulates its promoter. In the present study, by using DNA affinity chromatography and mass spectrometry, we have identified nucleolin as an additional protein that binds to a palindromic response region in the KLF2 promoter. The presence of nucleolin on the KLF2 promoter in macrophages was verified by electrophoretic mobility shift assays. Interestingly, in mouse and human endothelial cell lines, electrophoretic mobility shift assays and chromatin immunoprecipitation analyses indicated that nucleolin binds the KLF2 promoter only upon application of fluid shear stress. Pretreatment of the endothelial cells with LY294002, a specific inhibitor of phosphatidylinositol 3-kinase (PI3K), blocked the shear stress-induced binding of nucleolin to the promoter, demonstrating its PI3K-dependent regulation. Additionally, nucleolin exhibited dynamic flow-specific, PI3K-dependent alterations in size. Anti-nucleolin antibodies interacted with a 110-kDa form in static endothelial cells and with several catalytic forms that changed in abundance after the application of shear stress. Immunoprecipitation experiments demonstrated that fluid flow induced the interaction of nucleolin with the p85 regulatory subunit of PI3K. Finally, introduction of small interfering RNAs targeting the nucleolin genetic sequence selectively reduced nucleolin expression and was sufficient to block the induction of KLF2 by shear stress. These data support a general role for nucleolin in gene regulation and identify it as a novel factor involved in regulation of KLF2 expression.


Selecting High-Risk Individuals for Lung Cancer Screening: A Prospective Evaluation of Existing Risk Models and Eligibility Criteria in the German EPIC Cohort.
Lung cancer risk prediction models are considered more accurate than the eligibility criteria based on age and smoking in identification of high-risk individuals for screening. We externally validated four lung cancer risk prediction models (Bach, Spitz, LLP, and PLCO(M2012)) among 20,700 ever smokers in the EPIC-Germany cohort. High-risk subjects were identified using the eligibility criteria applied in clinical trials (NELSON/LUSI, DLCST, ITALUNG, DANTE, and NLST) and the four risk prediction models. Sensitivity, specificity, and positive predictive value (PPV) were calculated based on the lung cancers diagnosed in the first 5 years of follow-up. Decision curve analysis was performed to compare net benefits. The number of high-risk subjects identified by the eligibility criteria ranged from 3,409 (NELSON/LUSI) to 1,458 (NLST). Among the eligibility criteria, the DLCST produced the highest sensitivity (64.13%), whereas the NLST produced the highest specificity (93.13%) and PPV (2.88%). The PLCO(M2012) model showed the best performance in external validation (C-index: 0.81; 95% CI, 0.76-0.86; E/O: 1.03; 95% CI, 0.87-1.23) and the highest sensitivity, specificity, and PPV, but the superiority over the Bach model and the LLP model was modest. All the models but the Spitz model showed greater net benefit over the full range of risk estimates than the eligibility criteria. We concluded that all of the lung cancer risk prediction models apart from the Spitz model have a similar accuracy to identify high-risk individuals for screening, but in general outperform the eligibility criteria used in the screening trials.


Isolation and characterization of a heavy metal- and antibiotic-tolerant novel bacterial strain from a contaminated culture plate of Chlamydomonas reinhardtii, a green micro-alga.
Background:Chlamydomonas reinhardtii, a green micro-alga, is normally cultured in laboratories in Tris-Acetate Phosphate (TAP), a medium which contains acetate as the sole carbon source. Acetate in TAP can lead to occasional bacterial and fungal contamination. We isolated a yellow-pigmented bacterium from a Chlamydomonas TAP plate. It was named Clip185 based on the Chlamydomonas strain plate it was isolated from. In this article we present our work on the isolation, taxonomic identification and physiological and biochemical characterizations of Clip185. Methods: We measured sensitivities of Clip185 to five antibiotics and performed standard microbiological tests to characterize it. We partially sequenced the 16S rRNA gene of Clip185. We identified the yellow pigment of Clip185 by spectrophotometric analyses. We tested tolerance of Clip185 to six heavy metals by monitoring its growth on Lysogeny Broth (LB) media plates containing 0.5 mM -10 mM concentrations of six different heavy metals. Results: Clip185 is an aerobic, gram-positive rod, oxidase-negative, mesophilic, alpha-hemolytic bacterium. It can ferment glucose, sucrose and mannitol. It is starch hydrolysis-positive. It is very sensitive to vancomycin but resistant to penicillin and other bacterial cell membrane- and protein synthesis-disrupting antibiotics. Clip185 produces a C50 carotenoid, decaprenoxanthin, which is a powerful anti-oxidant with a commercial demand. Decaprenoxanthin production is induced in Clip185 under light. NCBI-BLAST analyses of the partial 16S rRNA gene sequence of Clip185 revealed a 99% sequence identity to that of Microbacterium binotii strain PK1-12M and Microbacterium sp. strain MDP6. Clip185 is able to tolerate toxic concentrations of six heavy metals. Conclusions: Our results show that Clip185 belongs to the genus Microbacterium. In the future, whole genome sequencing of Clip185 will clarify if Clip185 is a new Microbacterium species or a novel strain of Microbacterium binotii, and will reveal its genes involved in antibiotic-resistance, heavy-metal tolerance and regulation of decaprenoxanthin biosynthesis.


Melanotrope secretory cycle is regulated by physiological inputs via the hypothalamus.
Previously, it has been shown that background color conditions regulate the overall activity of the frog intermediate lobe by varying the proportions of the two subtypes of melanotropes existing in the gland, the highly active or secretory melanotropes and hormone storage melanotropes, depending on melanocyte-stimulating hormone requirements. However, the factors and mechanisms underlying these background-induced changes are still unknown. In the present study, we investigated whether hypothalamic factors known to regulate melanotrope cell function can induce changes in vitro similar to those caused by background adaptation in vivo. We found that the inhibitors apomorphine (a dopamine receptor agonist) and neuropeptide Y decreased the number of active melanotropes and increased simultaneously that of storage melanotropes. On the other hand, the stimulator TRH increased the number of active cells and concomitantly reduced that of storage cells. Inasmuch as none of these treatments modified the apoptotic and proliferation rates in melanotrope cells, it appears that these hypothalamic factors caused actual interconversions of cells from a subpopulation to its counterpart. Taken together, these findings suggest that the hypothalamus would control melanotrope activity not only through short-term regulation of hormone synthesis and release, but also through a long-term regulation of the secretory phenotype of these cells whereby the activity of the intermediate lobe would be adjusted to fulfill the hormonal requirements imposed by background conditions.


Pantophysin is a ubiquitously expressed synaptophysin homologue and defines constitutive transport vesicles.
Certain properties of the highly specialized synaptic transmitter vesicles are shared by constitutively occurring vesicles. We and others have thus identified a cDNA in various nonneuroendocrine cell types of rat and human that is related to synaptophysin, one of the major synaptic vesicle membrane proteins, which we termed pantophysin. Here we characterize the gene structure, mRNA and protein expression, and intracellular distribution of pantophysin. Its mRNA is detected in murine cell types of nonneuroendocrine as well as of neuroendocrine origin. The intron/exon structure of the murine pantophysin gene is identical to that of synaptophysin except for the last intron that is absent in pantophysin. The encoded polypeptide of calculated mol wt 28,926 shares many sequence features with synaptophysin, most notably the four hydrophobic putative transmembrane domains, although the cytoplasmic end domains are completely different. Using antibodies against the unique carboxy terminus pantophysin can be detected by immunofluorescence microscopy in both exocrine and endocrine cells of human pancreas, and in cultured cells, colocalizing with constitutive secretory and endocytotic vesicle markers in nonneuroendocrine cells and with synaptophysin in cDNA-transfected epithelial cells. By immunoelectron microscopy, the majority of pantophysin reactivity is detected at vesicles with a diameter of < 100 nm that have a smooth surface and an electron-translucent interior. Using cell fractionation in combination with immunoisolation, these vesicles are enriched in a light fraction and shown to contain the cellular vSNARE cellubrevin and the ubiquitous SCAMPs in epithelial cells and synaptophysin in neuroendocrine or cDNA-transfected nonneuroendocrine cells and neuroendocrine tissues. Pantophysin is therefore a broadly distributed marker of small cytoplasmic transport vesicles independent of their content.


Usefulness of percutaneous endoscopic gastrostomy for supportive therapy of advanced aerodigestive cancer.
Aerodigestive cancer, like esophageal cancer or head and neck cancer, is well known to have a poor prognosis. It is often diagnosed in the late stages, with dysphagia being the major symptom. Insufficient nutrition and lack of stimulation of the intestinal mucosa may worsen immune compromise due to toxic side effects. A poor nutritional status is a significant prognostic factor for increased mortality. Therefore, it is most important to optimize enteral nutrition in patients with aerodigestive cancer before and during treatment, as well as during palliative treatment. Percutaneous endoscopic gastrostomy (PEG) may be useful for nutritional support. However, PEG tube placement is limited by digestive tract stenosis and is an invasive endoscopic procedure with a risk of complications. There are three PEG techniques. The pull/push and introducer methods have been established as standard techniques for PEG tube placement. The modified introducer method, namely the direct method, allows for direct placement of a larger button-bumper-type catheter device. PEG tube placement using the introducer method or the direct method may be a much safer alternative than the pull/push method. PEG may be recommended in patients with aerodigestive cancer because of the improved complication rate.


Guanine nucleotide regulation of phospholipase C activity in permeabilized rabbit neutrophils. Inhibition by pertussis toxin and sensitization to submicromolar calcium concentrations.
Rabbit neutrophils labelled with [3H]inositol and permeabilized with saponin produced [3H]inositol trisphosphate (InsP3) when incubated with stable analogues of GTP or millimolar concentrations of Ca2+. [3H]InsP3 production elicited by guanosine 5'-[gamma-thio]triphosphate was enhanced by the chemoattractant formylmethionyl-leucyl-phenylalanine and inhibited by pertussis-toxin pretreatment. A pertussis-toxin-sensitive stimulation of [3H]InsP3 concentration was also observed with guanosine 5'-[beta gamma-imido]triphosphate, but not with guanosine 5'-[beta-thio]diphosphate or GTP. Millimolar Ca2+ alone was sufficient to stimulate [3H]InsP3 production; however, in the presence of guanosine 5'-[gamma-thio]triphosphate, the Ca2+ dose-response curve was shifted to submicromolar concentrations. These findings directly confirm the role of a pertussis-toxin-sensitive guanine nucleotide regulatory protein (G protein) in chemoattractant-stimulated phospholipase C activity in rabbit neutrophils. Moreover, the ability of guanine nucleotides to sensitize phospholipase C to physiologically relevant Ca2+ concentrations suggests that the role of the activated G protein may be to enhance the apparent affinity of phospholipase C for Ca2+ and thus to activate the enzyme without an increase in the Ca2+ concentration.


[Malignant neoplasms in kidney transplant recipients].
This study is a retrospective analysis of malignant tumors in renal transplant recipients. A review of the pertinent literature allowed us to develop a protocol for early diagnosis and treatment of tumors arising in this group of patients. 171 renal transplants have been performed over a period of 4 years. The renal grafts had been harvested from cadavers (mean age 32.01 years). All recipients (mean age 44.3 years) were immunosuppressed with prednisone, azathioprine and cyclosporine A. Five "de novo" malignant tumors were detected in 4 patients (2.3%). The tumors were basal cell epithelioma of scalp and gastric adenocarcinoma in the same patient, lymphoma of the CNS, carcinoma of the breast and adenocarcinoma of the colon. The patient with a gastric adenocarcinoma died after a disease-free interval of 28 months, following treatment of the cutaneous lesion. The patient with lymphoma of the CNS had died before receiving treatment and the remaining 2 patients are disease-free at 12 and 6 months' follow-up. The possible role of viruses is underscored. Transplant recipients should be followed very closely since they are likely to develop a tumor, especially of skin and lips. The importance of gynecological and neurological assessment and control of native kidneys cannot be overemphasized. Performing an autopsy on donors can reduce the risk of transplanting tumors. Kidney transplantation should be delayed if the graft recipient has a tumor. Correct diagnosis and treatment will enhance the results in these patients.


A potential role for RNA interference in controlling the activity of the human LINE-1 retrotransposon.
Long interspersed nuclear elements (LINE-1 or L1) comprise 17% of the human genome, although only 80-100 L1s are considered retrotransposition-competent (RC-L1). Despite their small number, RC-L1s are still potential hazards to genome integrity through insertional mutagenesis, unequal recombination and chromosome rearrangements. In this study, we provide several lines of evidence that the LINE-1 retrotransposon is susceptible to RNA interference (RNAi). First, double-stranded RNA (dsRNA) generated in vitro from an L1 template is converted into functional short interfering RNA (siRNA) by DICER, the RNase III enzyme that initiates RNAi in human cells. Second, pooled siRNA from in vitro cleavage of L1 dsRNA, as well as synthetic L1 siRNA, targeting the 5'-UTR leads to sequence-specific mRNA degradation of an L1 fusion transcript. Finally, both synthetic and pooled siRNA suppressed retrotransposition from a highly active RC-L1 clone in cell culture assay. Our report is the first to demonstrate that a human transposable element is subjected to RNAi.


Surrogate Markers of Abdominal Aortic Aneurysm Progression.
The natural course of many abdominal aortic aneurysms (AAA) is to gradually expand and eventually rupture and monitoring the disease progression is essential to their management. In this publication, we review surrogate markers of AAA progression. AAA diameter remains the most widely used and important marker of AAA growth. Standardized reporting of reproducible methods of measuring AAA diameter is essential. Newer imaging assessments, such as volume measurements, biomechanical analyses, and functional and molecular imaging, as well as circulating biomarkers, have potential to add important information about AAA progression. Currently, however, there is insufficient evidence to recommend their routine use in clinical practice.


Constitutive expression of various xenobiotic and endobiotic transporter mRNAs in the choroid plexus of rats.
The aim of this study was to quantitatively determine the constitutive expression levels of various transporter mRNAs in rat choroid plexus. To provide a reference for the relative expression levels, the expression of various transporter mRNAs in choroid plexus were compared with that in liver, kidney, and ileum. The mRNA levels of multidrug resistance protein (Mrp)1, 2, 3, 4, 5, and 6; multidrug resistance (Mdr)1a, 1b, and 2; organic anion transporting polypeptide (Oatp)1, 2, 3, 4, 5, 9, 12, and Oat-K (1/2); organic anion transporter (Oat)1, 2, and 3; organic cation transporter (Oct)1, 2, 3, N1, and N2; bile acid transporters sodium taurocholate cotransporting polypeptide (Ntcp), bile salt excretory protein (Bsep), and ileal bile acid transporter (Ibat); divalent metal transporter 1 (DMT1), Menke's and Wilson's metal transporters; equilibrative nucleotide transporters (Ent) 1 and 2, and constitutive nucleotide transporters (Cnt)1 and 2; peptide transporters (Pept)1 and 2; as well as ATP-binding cassette (Abc)G5 and 8 were measured in choroid plexus by the branched DNA signal amplification method. Mrp1, 4, and 5, Oatp3, Menke's transporter, DMT1, Ent1, and Pept2 mRNAs were expressed in choroid plexus at higher levels than in liver, kidney, or ileum. OctN1 and N2, Oatp2, Oat2 and 3, and Cnt1 and 2 mRNAs expressions were detectable in choroid plexus, but the levels were lower compared with that in liver, kidney, or ileum. The remaining transporters [Mrp2, Mrp3, Oct1, Oct2, Oatp1, Oatp4, Oatp5, Oatp12, Oat-K (1/2), Ntcp, Bsep, Ibat, Mdr1a, Mdr1b, Mdr2, Oat1, Ent2, Pept1, AbcG5, AbcG8] were expressed at very low levels in choroid plexus. The constitutive expression levels of different transporters in choroid plexus may provide an insight into the range of xenobiotics that can potentially be transported by the choroid plexus, thereby providing a means of xenobiotic detoxification in the brain.


Abnormal sinus node function in clinical arrhythmias.
To understand abnormal sinus node function in clinical atrial arrhythmias, it is essential to understand the normal function of the sinus node. Much of our understanding of the sinus node comes from work done in rabbits. In small animals, the node is a thin structure and can be modeled in two dimensions. However, in canines and humans, the node is a more complex structure completely surrounded by myocytes. Recent data suggest that the node may be insulated from the surrounding atrial myocytes, except at a limited number of exit sites. A model of the node with discrete exit sites explains how atrial activation can be initiated from multiple sites simultaneously. Within the node there may exist specialized pathways that explain the complex conduction within the node. Multiple cell types, with different intrinsic rates, combined with the nonuniform distribution of autonomic receptors, provide a basis for understanding the dynamics of heart rate control and the initiation of atrial activation. In addition, this model of the sinus node provides a framework to propose novel mechanisms underlying various atrial arrhythmias, such as atrial premature depolarizations or sinus node reentry.


Binding of alpha2-macroglobulin and limulin: regulation of the plasma haemolytic system of the American horseshoe crab, Limulus.
The mediator of haemolysis in the plasma of the horseshoe crab, Limulus polyphemus, is limulin, a sialic acid-binding lectin. The haemolytic activity of limulin is inhibited by thiol ester-reacted forms of Limulus alpha(2)-macroglobulin, the third-most abundant protein of the plasma. Limulus alpha(2)-macroglobulin that has experienced cleavage of its internal thiol ester bond, consequent to reaction with proteases, or with the small primary amine, methylamine, reduces the haemolytic activity of limulin when present at molar excesses that approximate the relative concentrations of these two proteins in the plasma. Native, unreacted Limulus alpha(2)-macroglobulin has no effect on the haemolytic activity of limulin. Limulin binds thiol ester-reacted forms of Limulus alpha(2)-macroglobulin both in a solid-phase assay and in solution with an avidity 10-25 times higher than native, unreacted Limulus alpha(2)-macroglobulin. Protease-reacted alpha(2)-macroglobulin functions as a marker for the presence of foreign proteases in the blood of Limulus, and thus of pathogenic organisms that release proteases as facilitators of invasion and pathogenicity. Modulation of the haemolytic system represents a novel function for alpha(2)-macroglobulin.


Airway Epithelial Cell Immunity Is Delayed During Rhinovirus Infection in Asthma and COPD.
Respiratory viral infections, particularly those caused by rhinovirus, exacerbate chronic respiratory inflammatory diseases, such as asthma and chronic obstructive pulmonary disease (COPD). Airway epithelial cells are the primary site of rhinovirus replication and responsible of initiating the host immune response to infection. Numerous studies have reported that the anti-viral innate immune response (including type I and type III interferon) in asthma is less effective or deficient leading to the conclusion that epithelial innate immunity is a key determinant of disease severity during a rhinovirus induced exacerbation. However, deficient rhinovirus-induced epithelial interferon production in asthma has not always been observed. We hypothesized that disparate in vitro airway epithelial infection models using high multiplicity of infection (MOI) and lacking genome-wide, time course analyses have obscured the role of epithelial innate anti-viral immunity in asthma and COPD. To address this, we developed a low MOI rhinovirus model of differentiated primary epithelial cells obtained from healthy, asthma and COPD donors. Using genome-wide gene expression following infection, we demonstrated that gene expression patterns are similar across patient groups, but that the kinetics of induction are delayed in cells obtained from asthma and COPD donors. Rhinovirus-induced innate immune responses were defined by interferons (type-I, II, and III), interferon response factors (IRF1, IRF3, and IRF7), TLR signaling and NF-κB and STAT1 activation. Induced gene expression was evident at 24 h and peaked at 48 h post-infection in cells from healthy subjects. In contrast, in cells from donors with asthma or COPD induction was maximal at or beyond 72-96 h post-infection. Thus, we propose that propensity for viral exacerbations of asthma and COPD relate to delayed (rather than deficient) expression of epithelial cell innate anti-viral immune genes which in turns leads to a delayed and ultimately more inflammatory host immune response.


Preliminary Experiments on a Microbial Fuel Cell.
Experiments were initiated to determine whether microbes using a hydrocarbon as food could generate electrical energy. Experiments with ethane were unsuccessful, but when microbes or glucose oxidase were added to a solution of glucose, electrical output was observed, confirming in part previous observations. As far as we know, no one had previously tested hydrocarbons in this manner, although the several effects of microbial activity on redox potential are well known. Failure of the microbes employed to dehydrogenate ethane in the absence of molecular oxygen is discussed in the light of recently published experimental evidence.


Improving structure-based virtual screening performance via learning from scoring function components.
Scoring functions (SFs) based on complex machine learning (ML) algorithms have gradually emerged as a promising alternative to overcome the weaknesses of classical SFs. However, extensive efforts have been devoted to the development of SFs based on new protein-ligand interaction representations and advanced alternative ML algorithms instead of the energy components obtained by the decomposition of existing SFs. Here, we propose a new method named energy auxiliary terms learning (EATL), in which the scoring components are extracted and used as the input for the development of three levels of ML SFs including EATL SFs, docking-EATL SFs and comprehensive SFs with ascending VS performance. The EATL approach not only outperforms classical SFs for the absolute performance (ROC) and initial enrichment (BEDROC) but also yields comparable performance compared with other advanced ML-based methods on the diverse subset of Directory of Useful Decoys: Enhanced (DUD-E). The test on the relatively unbiased actives as decoys (AD) dataset also proved the effectiveness of EATL. Furthermore, the idea of learning from SF components to yield improved screening power can also be extended to other docking programs and SFs available.


[Morphology of hairs on the head and other parts of the body in the residents of Africa].
The morphology of hairs from the head, beard, chest, armpits, and pubis was studied in indigenous population of Sudan, Sierra-Leone, Cote d'Ivoir, Ruanda, Nigeria, Gambia, Kenya, Uganda, Burundi, Zaire, Southern African Republic, Angola, Benin, and Guinea Bissau. A total of 327 hair specimens were examined. A number of new parameters of hairs were determined: thickness, number of cuticle pattern lines per mm, optic edge pattern, cuticle patterns, methods for detecting the cortical and medullar layers, width of hair layers and their transverse sections. The resultant morphological signs are new specific signs for African residents (Negroid) which can be used in forensic medical studies for identifying the race appurtenance of hairs.


Natural cilia-associated respiratory bacillus infection in rabbits used for elaboration of hyperimmune serum against Mycoplasma sp.
Cilia-associated respiratory (CAR) bacillus was identified in lung lesions of rabbits used for elaboration of hyperimmune serum against Mycoplasma mycoides ssp. capri (Mmc). Numerous Warthin Starry (WS) positive filamentous bacteria aligned perpendicularly to the surface of bronchial epithelial lining were observed. Immunoperoxidase staining of these bacteria was detected using a serum anti-rabbit CAR bacillus. Ultrastructural morphology corresponds to that of CAR bacilli previously reported in rabbits. The desirability of monitoring laboratory rabbits for CAR bacillus infection as part of the health programme is reinforced, especially in rabbits used for raising sera against respiratory pathogens of animal species in which CAR bacillus infection has been described. This is the first report of natural CAR bacillus infection in rabbits in Europe.


Effect of long-term omega 3 polyunsaturated fatty acid supplementation with or without multidomain intervention on cognitive function in elderly adults with memory complaints (MAPT): a randomised, placebo-controlled trial.
No large trials have been done to investigate the efficacy of an intervention combining a specific compound and several lifestyle interventions compared with placebo for the prevention of cognitive decline. We tested the effect of omega 3 polyunsaturated fatty acid supplementation and a multidomain intervention (physical activity, cognitive training, and nutritional advice), alone or in combination, compared with placebo, on cognitive decline. The Multidomain Alzheimer Preventive Trial was a 3-year, multicentre, randomised, placebo-controlled superiority trial with four parallel groups at 13 memory centres in France and Monaco. Participants were non-demented, aged 70 years or older, and community-dwelling, and had either relayed a spontaneous memory complaint to their physician, limitations in one instrumental activity of daily living, or slow gait speed. They were randomly assigned (1:1:1:1) to either the multidomain intervention (43 group sessions integrating cognitive training, physical activity, and nutrition, and three preventive consultations) plus omega 3 polyunsaturated fatty acids (ie, two capsules a day providing a total daily dose of 800 mg docosahexaenoic acid and 225 mg eicosapentaenoic acid), the multidomain intervention plus placebo, omega 3 polyunsaturated fatty acids alone, or placebo alone. A computer-generated randomisation procedure was used to stratify patients by centre. All participants and study staff were blinded to polyunsaturated fatty acid or placebo assignment, but were unblinded to the multidomain intervention component. Assessment of cognitive outcomes was done by independent neuropsychologists blinded to group assignment. The primary outcome was change from baseline to 36 months on a composite Z score combining four cognitive tests (free and total recall of the Free and Cued Selective Reminding test, ten Mini-Mental State Examination orientation items, Digit Symbol Substitution Test, and Category Naming Test) in the modified intention-to-treat population. The trial was registered with ClinicalTrials.gov (NCT00672685). 1680 participants were enrolled and randomly allocated between May 30, 2008, and Feb 24, 2011. In the modified intention-to-treat population (n=1525), there were no significant differences in 3-year cognitive decline between any of the three intervention groups and the placebo group. Between-group differences compared with placebo were 0·093 (95% CI 0·001 to 0·184; adjusted p=0·142) for the combined intervention group, 0·079 (-0·012 to 0·170; 0·179) for the multidomain intervention plus placebo group, and 0·011 (-0·081 to 0·103; 0·812) for the omega 3 polyunsaturated fatty acids group. 146 (36%) participants in the multidomain plus polyunsaturated fatty acids group, 142 (34%) in the multidomain plus placebo group, 134 (33%) in the polyunsaturated fatty acids group, and 133 (32%) in the placebo group had at least one serious emerging adverse event. Four treatment-related deaths were recorded (two in the multidomain plus placebo group and two in the placebo group). The interventions did not raise any safety concerns and there were no differences between groups in serious or other adverse events. The multidomain intervention and polyunsaturated fatty acids, either alone or in combination, had no significant effects on cognitive decline over 3 years in elderly people with memory complaints. An effective multidomain intervention strategy to prevent or delay cognitive impairment and the target population remain to be determined, particularly in real-world settings. French Ministry of Health, Pierre Fabre Research Institute, Gerontopole, Exhonit Therapeutics, Avid Radiopharmaceuticals.


Enhancing dye-sensitized solar cell performances by molecular engineering: highly efficient π-extended organic sensitizers.
This study deals with the synthesis and characterization of two π-extended organic sensitizers (G1 and G2) for applications in dye-sensitized solar cells. The materials are designed with a D-A-π-A structure constituted by i) a triarylamine group as the donor part, ii) a dithienyl-benzothiadiazole chromophore followed by iii) a further ethynylene-thiophene (G1) or ethynylene-benzene (G2) π-spacer and iv) a cyano-acrylic moiety as acceptor and anchoring part. An unusual structural extension of the π-bridge characterizes these structures. The so-configured sensitizers exhibit a broad absorption profile, the origin of which is supported by density functional theory. The absence of hypsochromic shifts as a consequence of deprotonation as well as notable optical and electrochemical stabilities are also observed. Concerning the performances in devices, electrochemical impedance spectroscopy indicates that the structural modification of the π-spacer mainly increases the electron lifetime of G2 with respect to G1. In devices, this feature translates into a superior power conversion efficiency of G2, reaching 8.1%. These results are comparable to those recorded for N719 and are higher with respect to literature congeners, supporting further structural engineering of the π-bridge extension in the search for better performing π-extended organic sensitizers.


Comparative impact of an anthranilic diamide and other insecticidal chemistries on beneficial invertebrates and ecosystem services in turfgrass.
Chlorantraniliprole, the first anthranilic diamide insecticide labeled for turf, combines strong selective activity against key pests with low vertebrate toxicity. The hypothesis that it is less disruptive to beneficial invertebrates and their ecosystem services than are other prevailing insecticide classes was tested. Plots in golf course settings were treated with chlorantraniliprole, or with a representative nicotinoid (clothianidin), pyethroid (bifenthrin) or a combination (clothianidin-bifenthrin) formulation. Non-target effects were assessed via pitfall traps (epigeal predators), Tullgren funnel extraction (soil microarthropods), hand sorting (earthworms), counting ant mounds and earthworm casts on tees and putting greens, assessing predation on sentinel pest eggs and comparing grass clipping decomposition in treated versus untreated turf. Chlorantraniliprole had little or, in most cases, no impact on predatory or soil invertebrates, predation or decomposition. Each of the other insecticides temporarily reduced abundance and activity of one or more predator groups. Clothianidin and the clothianidin-bifenthrin combination retarded grass clipping decomposition, and the combination suppressed earthworms and casts more than did carbaryl, a toxic standard. Chlorantraniliprole is compatible with conservation biocontrol and a good fit for industry initiatives to use relatively less toxic pesticides. One caveat is that its use on golf courses may require targeted management of ant mounds and earthworm casts that are suppressed as a side effect by some less selective insecticides.


A simple method to generate adipose stem cell-derived neurons for screening purposes.
Strategies involved in mesenchymal stem cell (MSC) differentiation toward neuronal cells for screening purposes are characterized by quality and quantity issues. Differentiated cells are often scarce with respect to starting undifferentiated population, and the differentiation process is usually quite long, with high risk of contamination and low yield efficiency. Here, we describe a novel simple method to induce direct differentiation of MSCs into neuronal cells, without neurosphere formation. Differentiated cells are characterized by clear morphological changes, expression of neuronal specific markers, showing functional response to depolarizing stimuli and electrophysiological properties similar to those of developing neurons. The method described here represents a valuable tool for future strategies aimed at personalized screening of therapeutic agents in vitro.


Biphasic activation of the mTOR pathway in the gustatory cortex is correlated with and necessary for taste learning.
Different forms of memories and synaptic plasticity require synthesis of new proteins at the time of acquisition or immediately after. We are interested in the role of translation regulation in the cortex, the brain structure assumed to store long-term memories. The mammalian target of rapamycin, mTOR (also known as FRAP and RAFT-1), is part of a key signal transduction mechanism known to regulate translation of specific subset of mRNAs and to affect learning and synaptic plasticity. We report here that novel taste learning induces two waves of mTOR activation in the gustatory cortex. Interestingly, the first wave can be identified both in synaptoneurosomal and cellular fractions, whereas the second wave is detected in the cellular fraction but not in the synaptic one. Inhibition of mTOR, specifically in the gustatory cortex, has two effects. First, biochemically, it modulates several known downstream proteins that control translation and reduces the expression of postsynaptic density-95 in vivo. Second, behaviorally, it attenuates long-term taste memory. The results suggest that the mTOR pathway in the cortex modulates both translation factor activity and protein expression, to enable normal taste memory consolidation.


Leprosy control in Zambia.
Leprosy was a serious public health problem in Zambia until recently, with over 16,000 cases in 1982. Since then leprosy patients in the country have been put under multidrug therapy (MDT), as recommended by WHO, with support from the Sasakawa Memorial Health Foundation. Leprosy control in Zambia is combined with tuberculosis control and integrated within general health services. By 1990 52 districts (93%) had MDT, with an overall coverage of about 70% of all patients. As a result the number of registered cases has come down steadily from 16,642 in 1982 to 3,663 in 1989. Similarly, the number of new cases detected has been reduced from 1,010 cases in 1982 to 577 in 1989. On the whole the programme has gained significant momentum, although it is too early to expect a complete eradication of the disease in the near future, given the continued low level of observed new cases. Further, the implementation of MDT still lags behind the projected targets so that the potential of MDT is not being fully utilized. In addition, the problem of rehabilitation of disabled patients needs special attention. A subprogramme aimed at reducing disability through community participation is being developed within the framework of primary health care.


Molecular evolution of the Chlamydiaceae.
Phylogenetic analyses of surface antigens and other chlamydial proteins were used to reconstruct the evolution of the Chlamydiaceae. Trees for all five coding genes [the major outer-membrane protein (MOMP), GroEL chaperonin, KDO-transferase, small cysteine-rich lipoprotein and 60 kDa cysteine-rich protein] supported the current organization of the family Chlamydiaceae, which is based on ribosomal, biochemical, serological, ecological and DNA-DNA hybridization data. Genetic distances between some species were quite large, so phylogenies were evaluated for robustness by comparing analyses of both nucleotide and protein sequences using a variety of algorithms (neighbour-joining, maximum-likelihood, maximum-parsimony with bootstrapping, and quartet puzzling). Saturation plots identified areas of the trees in which factors other than relatedness may have determined branch attachments. All nine species were clearly differentiated by distinctness ratios calculated for each gene. The distribution of virulence traits such as host and tissue tropism were mapped onto the consensus phylogeny. Closely related species were no more likely to share virulence characters than were more distantly related species. This phylogenetically disjunct distribution of virulence traits could not be explained by lateral transfer of the genes we studied, since we found no evidence for lateral gene transfer above the species level. One interpretation of this observation is that when chlamydiae gain access to a new niche, such as a new host or tissue, significant adaptation ensues and the virulence phenotype of the new species reflects adaptation to its environment more strongly than it reflects its ancestry.


Gender effects of acute malathion or zinc exposure on the antioxidant response of rat hippocampus and cerebral cortex.
Gender is one of the most important factors in mammalian development and response to exogenous agents. Although there is increasing evidence that health effects of toxic xenobiotics differ in prevalence or are manifested differently in male and female, the molecular mechanisms related to these events remain unclear. In order to investigate the possible influence of gender, male and female Wistar rats from the same litter were exposed to zinc chloride (5 mg/kg, i.p.) or malathion (250 mg/kg, i.p.) 24 hr prior to the analyses of biochemical parameters related to the cholinergic and glutathione-antioxidant systems in cerebral cortex and hippocampus. After treatments, acetylcholinesterase (AChE) activity was reduced in the hippocampus and cerebral cortex of male and female rats treated with malathion, but the effect was more pronounced in the male group. Glutathione reductase (GR) and γ-glutamyl-transpeptidase activities were reduced in the hippocampus of males and females and a gender-specific effect of malathion was seen for glutathione S-transferase (GST), which was decreased only in male hippocampus and cortex, and for male cortical GR. Zinc chloride treatment decreased AChE activity in male and female cerebral cortex, with no obvious effect in the hippocampus. Male-specific antioxidant-related enzyme activity reductions were seen after zinc treatment for cortical GR, GST, glutathione peroxidase and glucose-6-phosphate dehydrogenase; and hippocampal GR. These results clearly demonstrate a greater detrimental effect on antioxidant-related enzyme activities in male hippocampus and cerebral cortex when rats were acutely exposed to malathion and zinc, demonstrating that the research on gender-related differences in health effects caused by xenobiotic and/or essential elements requires further attention.


The Effect of Titanium Dioxide Surface Modification on the Dispersion, Morphology, and Mechanical Properties of Recycled PP/PET/TiO2 PBNANOs.
Titanium dioxide (TiO2) nanoparticles have recently appeared in PET waste because of the introduction of opaque PET bottles. We prepare polymer blend nanocomposites (PBNANOs) by adding hydrophilic (hphi), hydrophobic (hpho), and hydrophobically modified (hphoM) titanium dioxide (TiO2) nanoparticles to 80rPP/20rPET recycled blends. Contact angle measurements show that the degree of hydrophilicity of TiO2 decreases in the order hphi > hpho > hphoM. A reduction of rPET droplet size occurs with the addition of TiO2 nanoparticles. The hydrophilic/hydrophobic balance controls the nanoparticles location. Transmission electron microscopy (TEM_ shows that hphi TiO2 preferentially locates inside the PET droplets and hpho at both the interface and PP matrix. HphoM also locates within the PP matrix and at the interface, but large loadings (12%) can completely cover the surfaces of the droplets forming a physical barrier that avoids coalescence, leading to the formation of smaller droplets. A good correlation is found between the crystallization rate of PET (determined by DSC) and nanoparticles location, where hphi TiO2 induces the highest PET crystallization rate. PET lamellar morphology (revealed by TEM) is also dependent on particle location. The mechanical behavior improves in the elastic regime with TiO2 addition, but the plastic deformation of the material is limited and strongly depends on the type of TiO2 employed.


IL-1 Contributes to the Anti-Cancer Efficacy of Ingenol Mebutate.
Ingenol mebutate is approved for the topical treatment of actinic keratoses and may ultimately also find utility in treating skin cancers. Here we show that relapse rates of subcutaneous B16 melanoma tumours treated topically with ingenol mebutate were not significantly different in C57BL/6 and Rag1-/- mice, suggesting B and T cells do not play a major role in the anti-cancer efficacy of ingenol mebutate. Relapse rates were, however, significantly increased in MyD88-/- mice and in C57BL/6 mice treated with the anti-IL-1 agent, anakinra. Ingenol mebutate treatment induces a pronounced infiltration of neutrophils, which have been shown to have anti-cancer activity in mice. Herein we provide evidence that IL-1 promotes neutrophil recruitment to the tumour, decreases apoptosis of infiltrating neutrophils and increases neutrophil tumour killing activity. These studies suggest IL-1, via its action on neutrophils, promotes the anti-cancer efficacy of ingenol mebutate, with ingenol mebutate treatment causing both IL-1β induction and IL-1α released from keratinocytes.


[Severe lower digestive hemorrhage in Crohn's disease].
Severe or massive lower gastrointestinal bleeding is an unusual complication of inflammatory bowel disease that has traditionally associated with ulcerative colitis, although it can also appear in 0.6-2% of the cases in Crohn's disease. Two cases of severe lower gastrointestinal bleeding in Crohn's disease, one of them with ileocolic and another with ileal involvement are presented. Surgical treatment is supported by potential severity, high frequency of the relapse and data indicate a good prognosis after intestinal resection. It can be performed immediately if the persist bleeding or elective, as the 2 cases that we present, in the patients that are stabilized.


Prolonged reversal of long-term potentiation that is N-methyl-D-aspartate receptor independent: implications for memory formation.
Reversal of long-term potentiation (LTP) by low-frequency stimulation (LFS) is often referred to as depotentiation (DP), a phenomenon that is time-dependent. The present study aimed to determine whether LTP could still be reversed when the stimulation was applied beyond the optimal time window in hippocampal slices from adult rats. Field excitatory postsynaptic potentials (fEPSPs) were recorded from the strata radiatum in CA1, following stimulation of Schaffer collaterals. Theta-burst stimulation (TBS) induced LTP that could be reversed by repeated paired-pulse LFS (PP-LFS) after almost 3 h post-TBS. Only when synapse strength reached a plateau did application of PP-LFS trigger DP. In addition, it was surprising to observe that PP-LFS, which generally induces LTD in adult rats, evoked an LTP-like further strengthening in previously potentiationed synapses, even in the presence of APV, a competitive antagonist of N-methyl-D-aspartate receptors (NMDA-Rs). Our results suggest that LTP can be reversed NMDAR-independently more than 2 h after TBS by PP-LFS in adult hippocampus and that saturation of LTP is effective to promote this process.


Assessment of trends in biological and behavioural surveillance data: is there any evidence of declining HIV prevalence or incidence in Malawi?
In 2003 an estimated 87 000 AIDS deaths and approximately 110 000 new infections occurred in Malawi. This paper aimed to analyse and review HIV prevalence trends in conjunction with other second generation surveillance data including behavioural data and, therefore, to describe trends in HIV prevalence and behaviours related to HIV transmission. In order to determine the extent of the problem, HIV prevalence in Malawi has been monitored through testing women attending antenatal clinics in 19 sentinel sites consistently since 1994. These sites are classified as urban, semi-urban, and rural. The overall HIV prevalence for all 19 ANC sentinel sites in 2003 was 19.8% (95% CI 19.0% to 20.7%). The central region urban/semi-urban sites showed a decline in prevalence from 1999 to 2003. Since 1997, overall national incidence estimates remained stable. This stable incidence estimate is supported by the proxy of fairly stable prevalence in ANC attendees aged 15-24 years. HIV sentinel surveillance data for Lilongwe city showed a significant linear decline in prevalence (p<0.00001) over the last seven years for both all ANC attendees and those aged 15-24 years suggesting that incidence has declined over the time period. The available epidemiological and behavioural surveillance data show that HIV prevalence has declined in several urban and semi-urban areas, specifically in the central region with Lilongwe (capital of Malawi) showing exceptionally strong evidence of decline. In some rural areas, particularly in the northern region there is some evidence of an increasing trend in HIV prevalence.


Group size and direct fitness in social queues.
We explore the effects of group size on the direct reproductive success of subordinate helpers in eusocial animals where only a single, dominant individual reproduces at one time. Helpers can reproduce directly if they inherit dominance, but when dominance is age based, an individual born into a larger group has a longer wait to inherit. We show that this disincentive to help can potentially be offset by increased productivity, increased life span, and insurance-based benefits for helpers if they survive to inherit dominance in larger groups. We analyze a field experiment in which group size was manipulated in the hover wasp Liostenogaster flavolineata. Productivity increased linearly with group size, larger groups were less likely to fail, and dominants in larger groups may have lived longer. Combined with the probability of inheriting dominance, these effects led overall to a negative correlation between group size and expected direct fitness, mainly because group size decreased during our study period, so that helpers could not expect to inherit as large a group as they started queuing in. Our analysis suggests that the relationship between group size and productivity plays a central role in determining the fitness consequences of helping.


Presbyopia and near spectacle correction coverage among public school teachers in Ifo Township, South-West Nigeria.
Presbyopia is an age-related loss of lens accommodation resulting in difficulty in performing near task with attendant effect on the quality of life. The objective of the study was to determine the prevalence of presbyopia and presbyopic spectacle correction coverage among public school teachers in Ifo township, with a view to providing a baseline information that could be useful for advocacy and planning appropriate intervention. The study was a descriptive, cross-sectional study. Six hundred public school teachers aged 30 years and above were examined in 25 clusters using a multistage random sampling technique with probability proportional to size. Questionnaire was used to obtain information on demographic data, sources of spectacle and barriers to spectacle use. All participants underwent a standardised protocol including visual acuity assessment (distance and near acuity), anterior and posterior segment examinations and refraction. Six hundred teachers were examined with an age range of 30-61 years. The mean age was 44.7 ± 7.5 years and the male to female ratio was 1:2.2. The prevalence of presbyopia was 81.3% and 38.5% of the presbyopic teachers did not have presbyopic correction. However, the average age of onset of presbyopia was earlier in females 33 years compared to 36 years observed in males, although not statistically significant (P = 0.88). The presbyopic correction coverage was 61.5%. One hundred and eighty-six (62%) presbyopic teachers obtained their spectacle from opticians, and the main barriers to the use of near vision spectacle were lack of awareness (23.7%) and cost (13.7%). This study demonstrated a high prevalence of presbyopia among public school teachers in Ifo town, South-West Nigeria, but less presbyopic spectacle correction coverage.


Spontaneous propulsion of a water nanodroplet induced by a wettability gradient: a molecular dynamics simulation study.
The directional propulsion of liquid droplets at the nanoscale is quite an interesting topic of research in the fields of micro/nano-fluidics, water filtration, precision medicine, and cooling of electronics. In this study, the unidirectional spontaneous transport of a water nanodroplet on a solid surface with a multi-gradient surface (MGS) inspired by natural species is modeled and analyzed using molecular dynamics (MD) simulations. There are three different MGSs considered in this study containing different wedge angles of the hydrophilic region of the solid surface. The MGSs contain two regions: a hydrophilic wedge-shaped region with a constant surface energy parameter equal to 50 meV and a hydrophobic region with a tuned surface energy parameter. The energy parameter of the hydrophobic region is set equal to 1, 5, 10, 20, 30, and 40 meV in order to alter the intensity of the wettability gradient of the two surfaces and its effect on the propulsion of the water nanodroplet is analyzed. Furthermore, three different sizes of water droplets containing 6000, 8000, and 10 000 water molecules are also used in this study and their effect on the transport behavior of the water nanodroplet is also measured. Moreover, two different designs on a solid surface with a continuous wettability gradient are modelled and the impact of solid surface geometry on the transport of the water droplet is calculated by means of mean square displacement (MSD) and average velocity data. In addition, the wedge-shaped surface is found to be more superior to the parallel-shaped surface for the spontaneous propulsion of the water droplet.


Differentiation of hepatocellular adenoma and focal nodular hyperplasia of the liver: comparison of power Doppler imaging and conventional color Doppler sonography.
The aim of our study was to compare the diagnostic efficacy of power Doppler imaging and conventional color Doppler sonography for differentiating between hepatocellular adenoma (HCA) and focal nodular hyperplasia (FNH) of the liver. Thirty-one focal liver lesions (in 29 patients) with histologic proof of HCA (n = 9) or FNH (n = 22) were studied with power and color Doppler sonography according to a standardized examination protocol. The size of the lesions ranged between 1.5 and 14.5 cm (HCA, 3.5-14.5 cm, mean +/- SD 7.3 +/- 3.3 cm; FNH, 1.5-9.1 cm, mean +/- SD 5.1 +/- 2.1 cm). Intratumoral vessels with a venous Doppler spectrum, associated with either pulsatile or continuous peripheral flow, were detected in HCA (eight of nine lesions by power Doppler imaging and six of nine by color Doppler imaging) but not in FNH. In contrast, color signals with an arterial Doppler spectrum, radiating from the center to the periphery of the lesion, were depicted in FNH (20 of 22 cases by power Doppler imaging and 15 of 22 by color Doppler sonography) but not in HCA. Differentiation of HCA and FNH was achieved in 28 of 31 cases (90 %) by power Doppler imaging and in 21 of 31 (68 %) by color Doppler sonography (p < 0.01). Power Doppler imaging is superior to conventional color Doppler sonography in the depiction of the intratumoral flow characteristics of HCA and FNH, and enables a more accurate differential diagnosis than color Doppler sonography.


[Imitative models of the organization of treatment and evacuation measures conducted in the infantry regiment during combat].
During the combat the chief of medical service has to solve both the direct mission, i.e. to choose the most effective variant of organization of treatment-and-evacuation measures (TEM) and the indirect one, i.e. to define the needs of medical service in forces and resources according to the given model. To fulfill these missions the most effective method is the multi-criteria approach for practical realization of which the "successive steps" method was chosen. The main indicator of TEM effectiveness is the time from the wounding to the point of readiness for evacuation from the regimental aid station. The GPSS language of different dialects as the modelling environment is preferred on the basis of which two computerized imitative models were created: the model of TEM effectiveness in the company-battalion link and the model of regimental aid station work.


Cognitive impairment after chemotherapy related to atypical network architecture for executive control.
A common complaint of cancer patients is the experience of cognitive difficulty during and after chemotherapy. We hypothesized that cognitive impairment may result from dysfunction in large-scale brain networks, particularly those involved in attentional control. Using a case-control design, this study includes women with a history of invasive ductal or lobular triple-negative breast cancer who completed standard adjuvant chemotherapy within 2 years of study entry. Women who reported cognitive impairment by the Global Rating of Cognition question were considered to be cases (n = 15). Women who reported no cognitive impairment were considered to be controls (n = 13). All enrolled participants were eligible for MRI investigation and underwent resting-state functional connectivity MRI. Women who self-reported cognitive impairment were found to have disrupted resting-state functional connectivity, as measured by MRI, when compared to women who did not self-report cognitive impairment. These findings suggest that some women may be more sensitive to the standard treatments for breast cancer and that this increased sensitivity may result in functional connectivity alterations in the brain networks supporting attention and executive function. Neuroimaging analyses confirmed self-reported cognitive deficits in women with breast cancer treated with chemotherapy.


Biomechanical Comparison of Knotless All-Suture Anchors and Knotted All-Suture Anchors in Type II SLAP Lesions: A Cadaveric Study.
To compare the biomechanical performance of knotless versus knotted all-suture anchors for the repair of type II SLAP lesions with a simulated peel-back mechanism. Twenty paired cadaveric shoulders were used. A standardized type II SLAP repair was performed using knotless (group A) or knotted (group B) all-suture anchors. The long head of the biceps (LHB) tendon was loaded in a posterior direction to simulate the peel-back mechanism. Cyclic loading was performed followed by load-to-failure testing. Stiffness, load at 1 and 2 mm of displacement, load to repair failure, load to ultimate failure, and failure modes were assessed. The mean load to repair failure was similar in groups A (179.99 ± 58.42 N) and B (167.83 ± 44.27 N, P = .530). The mean load to ultimate failure was 230 ± 95.93 N in group A and 229.48 ± 78.45 N in group B and did not differ significantly (P = .958). Stiffness (P = .980), as well as load at 1 mm (P = .721) and 2 mm (P = .849) of displacement, did not differ significantly between groups. In 16 of the 20 specimens (7 in group A and 9 in group B), ultimate failure occurred at the proximal LHB tendon. Failed occurred through slippage of the labrum in 1 specimen in each group and through anchor pullout in 2 specimens in group A. Knotless and knotted all-suture anchors displayed high initial fixation strength with no significant differences between groups in type II SLAP lesions. Ultimate failure occurred predominantly as tears of the proximal LHB tendon. All-suture anchors have a smaller diameter than solid anchors, can be inserted through curved guides, preserve bone stock, and facilitate postoperative imaging. There is a paucity of literature investigating the biomechanical capacities of knotless versus knotted all-suture anchors in type II SLAP repair.


Endothelin-1 inhibits AVP-stimulated osmotic water permeability in rat inner medullary collecting duct.
Endothelin causes diuresis despite an accompanying decrease in glomerular filtration rate and renal plasma flow. Binding sites for endothelin are located not only in glomeruli but also in the inner medulla, possibly in inner medullary collecting ducts (IMCD). To determine whether endothelin has a direct tubular effect, effects of endothelin on water and urea transport were investigated using isolated microperfusion of rat IMCD segments in vitro. Endothelin, at 10(-10) and 10(-8) M, reversibly inhibited 10(-11) M arginine vasopressin (AVP)-stimulated osmotic water permeability (Pf) by 18 and 24%, respectively. Endothelin (10(-8) M) also inhibited Pf by 23% in the presence of a much higher dose of AVP (10(-9) M), whereas endothelin had no effect on Pf in the absence of AVP. On the other hand, 10(-8) M endothelin did not inhibit Pf stimulated by 10(-3) M dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP). Endothelin had no inhibitory effect on AVP-stimulated urea permeability. These data suggest that endothelin can cause diuresis by inhibiting AVP-stimulated Pf in IMCD and that the site of action is previous to cAMP generation.


Exploratory open-label clinical study to determine the S-588410 cancer peptide vaccine-induced tumor-infiltrating lymphocytes and changes in the tumor microenvironment in esophageal cancer patients.
Cancer vaccines induce cancer-specific T-cells capable of eradicating cancer cells. The impact of cancer peptide vaccines (CPV) on the tumor microenvironment (TME) remains unclear. S-588410 is a CPV comprising five human leukocyte antigen (HLA)-A*24:02-restricted peptides derived from five cancer testis antigens, DEPDC1, MPHOSPH1, URLC10, CDCA1 and KOC1, which are overexpressed in esophageal cancer. This exploratory study investigated the immunologic mechanism of action of subcutaneous S-588410 emulsified with MONTANIDE ISA51VG adjuvant (median: 5 doses) by analyzing the expression of immune-related molecules, cytotoxic T-lymphocyte (CTL) response and T-lymphocytes bearing peptide-specific T-cell receptor (TCR) sequencing in tumor tissue or blood samples from 15 participants with HLA-A*24:02-positive esophageal cancer. Densities of CD8+, CD8+ Granzyme B+, CD8+ programmed death-1-positive (PD-1+) and programmed death-ligand 1-positive (PD-L1+) cells were higher in post- versus pre-vaccination tumor tissue. CTL response was induced in all patients for at least one of five peptides. The same sequences of peptide-specific TCRs were identified in post-vaccination T-lymphocytes derived from both tumor tissue and blood, suggesting that functional peptide-specific CTLs infiltrate tumor tissue after vaccination. Twelve (80%) participants had treatment-related adverse events (AEs). Injection site reaction was the most frequently reported AE (grade 1, n = 1; grade 2, n = 11). In conclusion, S-588410 induces a tumor immune response in esophageal cancer. Induction of CD8+ PD-1+ tumor-infiltrating lymphocytes and PD-L1 expression in the TME by vaccination suggests S-588410 in combination with anti-PD-(L)1 antibodies may offer a clinically useful therapy.Trial registration UMIN-CTR registration identifier: UMIN000023324.


Individual cristae within the same mitochondrion display different membrane potentials and are functionally independent.
The mitochondrial membrane potential (ΔΨm ) is the main driver of oxidative phosphorylation (OXPHOS). The inner mitochondrial membrane (IMM), consisting of cristae and inner boundary membranes (IBM), is considered to carry a uniform ΔΨm . However, sequestration of OXPHOS components in cristae membranes necessitates a re-examination of the equipotential representation of the IMM. We developed an approach to monitor ΔΨm at the resolution of individual cristae. We found that the IMM was divided into segments with distinct ΔΨm , corresponding to cristae and IBM. ΔΨm was higher at cristae compared to IBM. Treatment with oligomycin increased, whereas FCCP decreased, ΔΨm heterogeneity along the IMM. Impairment of cristae structure through deletion of MICOS-complex components or Opa1 diminished this intramitochondrial heterogeneity of ΔΨm . Lastly, we determined that different cristae within the individual mitochondrion can have disparate membrane potentials and that interventions causing acute depolarization may affect some cristae while sparing others. Altogether, our data support a new model in which cristae within the same mitochondrion behave as independent bioenergetic units, preventing the failure of specific cristae from spreading dysfunction to the rest.


[X-ray diffraction studies of muscles].
A brief account of the modern state of X-ray diffraction studies of muscles is presented. Recently many investigaters payed particular attention to concrete changes taking place in structural-executive (protofibrillar) apparatus of muscles at the change of their state. The drawback of these works is the necessity of interpreting the data on the basis of model ideas having definite variability. Our studies here presented differe by the approach to the problem and to a certain extent by the methods applied. Our main task was to study the dynamics of structural changes in muscles while the latter perform their working function. Special attention was payed to the studies of muscles at different shortening eithor on living or fixed samples. The effect of some conventional fixators on structural parameters evaluated by X-ray analysis was studied for the first time. A means of stroboscopic accumulation of X-ray diffraction patterns for periodic fast processes was developed. One of our main tasks was to find the range of applicability sliding mechanism hypothesis for describing muscle shortening. It was observed that the sliding mechanism held true for the desscription of the structure of muscles shortened in a physiological range. X-ray diffraction patterns were obtained which were different for the shortenings according to the sliding mechanism and those with A-disc shortening and during supercontraction. The limits of the sliding model were evaluated by some of these characteristics for muscle of different composition and properties. The problem of the forces realizing muscle shortening is discussed, some of the author's studies being taken into account. Muscle should be assessed as a complex heteromorph biological object and as a complex liquid crystalline system to create the models of its molecular structure and to elucidate the precise mechanism of its functional activity.


Effects of maternal dexamethasone administration on fetal Doppler flow velocity waveforms.
To investigate the effects of maternal dexamethasone administration on umbilical and fetal cerebral artery flow velocity waveforms. Cross-sectional study. Department of Obstetrics and Gynaecology, Robert Ballanger Hospital, Aulnay-sous-Bois, France. Twenty-six pregnant women with singleton pregnancies considered at risk for preterm delivery. At baseline, all pregnancies had normal fetoplacental vascular resistance. These women were given weekly six intravenous doses of 4 mg of dexamethasone eight hours apart. Doppler studies were performed from both umbilical artery (UA) and fetal middle cerebral artery (MCA) before (day 0), during (day 2), immediately after (day 4) and shortly after (day 7) every steroid course. No significant variation was noted in both umbilical artery pulsatility index (PI) and fetal heart rate through dexamethasone therapy. Compared with mean initial values, we found on day 4 a significant decrease in MCA PI of 0.28 (F = 7.17, P < 0.001) and a significant increase in UA:MCA PI ratio of 0.08 (F = 3.85, P = 0.013); in contrast no significant change was documented on days 2 and 7 in both MCA pulsatility index and UA:MCA PI ratio. After multiple regression analysis, only the decrease in fetal middle cerebral artery pulsatility index on day 4 remained significant (F= 5.84, P= 0.001). The current study finds in healthy fetuses a transient, significant and unexplained decrease in fetal middle cerebral artery impedance on the fourth day following maternal dexamethasone administration. Further basic research and clinical studies including larger sample sizes or pregnancies with fetoplacental dysfunction are needed.


[Higher fatty acid composition of enterococci].
The content of unsaturated fatty acids in enterococcal cells has been found to have no essential relation to the composition of the culture medium. When cultivated in the same media, S. faecium had the degree of lipid unsaturation 1.5-2 times higher than S. faecalis. Mobile enterococci are sharply differentiated from immobile species by the content of cyclopropanic acid with 19 carbon atoms, constitute a heterogenous group and consist of at least 2 taxons, differing in the content of acids with 18 carbon atoms and the degree of lipid unsaturation.


Increased Mortality Among Renal Transplant Patients With Invasive Pulmonary Aspergillus Infection.
Renal transplantation is the most effective and preferred definite treatment option in patients with end-stage renal disease. Due to long-term immunesuppressive treatment, renal transplant recipients become vulnerable to opportunistic infections, especially to fungal infections. This was a single-center, retrospective observational study of 438 patients who underwent renal transplantation between 2010 and 2016. Thirty-eight renal transplant recipients who had lower respiratory tract infection with median age of 41.5 years were evaluated for invasive pulmonary aspergillus (IPA). Of these, 52.6% were female and 84.2% had living donors. Eleven of 38 lower respiratory patients were found to have IPA infection, 5 with proven infection. Compared to patients who did not have fungal pulmonary infection, patients with invasive aspergillus were older and had high fever, galactomannan levels, and leukocyte counts. Mortality was also higher in those patients. Having fever at the baseline and IPA infection was significantly associated with mortality in univariate analysis and remained related in multivariate model after adjustment for age, gender, and fever. Invasive pulmonary aspergillus infection is highly associated with increased mortality rates in renal transplant patients. Fungal pulmonary infections in immune-suppressed patients should be diagnosed and treated immediately in order to avoid the life-threatening complications and may greatly improve prognosis.


Impact of Chronic Diseases and Multimorbidity on Health and Health Care Costs: The Additional Role of Musculoskeletal Disorders.
Chronic diseases are increasingly prevalent and often occur as multimorbidity. This study compares the impact of musculoskeletal disorders (MSKDs) on health and health care costs with other chronic diseases, and assesses the additional impact of MSKDs on these outcomes when occurring as part of multimorbidity. A household survey in a random Dutch population sample (n = 8,904) yielded information on sociodemographics, presence of 9 physician-confirmed chronic diseases (i.e., musculoskeletal, migraine, diabetes mellitus, cardiovascular, cancer, respiratory, skin, mental, and gastrointestinal), physical component summary (PCS) and mental component summary (MCS) scores of the Short Form 12 health survey, and health care utilization. The independent influence of different diseases and the role of MSKDs with increasing number of morbidities on PCS/MCS and 3-month societal health care costs were explored through multivariable linear and zero-inflated negative binomial regressions, respectively. Twenty percent of all subjects and 56% of those with multimorbidity had an MSKD. MSKDs had the largest impact on PCS (β = -8.37 [95% confidence interval (95% CI) -8.84, -7.89]) but no significant impact on MCS. When MSKDs occurred as part of multimorbidity, an amplification of the adverse effect on PCS but not on MCS was seen, irrespective of the number of comorbidities. MSKDs were responsible for a 2-fold increase in costs (Exp [β] = 2.27 [95% CI 2.08, 2.51]), which was the second highest cost increase of all diseases (after cancer). Significant amplification of costs was seen when MSKDs co-occurred with mental diseases. MSKDs often co-occur with other chronic diseases. In the context of multimorbidity, presence of an MSKD amplifies the impact on physical health, and to a lesser extent on health care costs, but not on mental health.


Lipreading and covert speech production similarly modulate human auditory-cortex responses to pure tones.
Watching the lips of a speaker enhances speech perception. At the same time, the 100 ms response to speech sounds is suppressed in the observer's auditory cortex. Here, we used whole-scalp 306-channel magnetoencephalography (MEG) to study whether lipreading modulates human auditory processing already at the level of the most elementary sound features, i.e., pure tones. We further envisioned the temporal dynamics of the suppression to tell whether the effect is driven by top-down influences. Nineteen subjects were presented with 50 ms tones spanning six octaves (125-8000 Hz) (1) during "lipreading," i.e., when they watched video clips of silent articulations of Finnish vowels /a/, /i/, /o/, and /y/, and reacted to vowels presented twice in a row; (2) during a visual control task; (3) during a still-face passive control condition; and (4) in a separate experiment with a subset of nine subjects, during covert production of the same vowels. Auditory-cortex 100 ms responses (N100m) were equally suppressed in the lipreading and covert-speech-production tasks compared with the visual control and baseline tasks; the effects involved all frequencies and were most prominent in the left hemisphere. Responses to tones presented at different times with respect to the onset of the visual articulation showed significantly increased N100m suppression immediately after the articulatory gesture. These findings suggest that the lipreading-related suppression in the auditory cortex is caused by top-down influences, possibly by an efference copy from the speech-production system, generated during both own speech and lipreading.


CYP3A isoforms in Ewing's sarcoma tumours: an immunohistochemical study with clinical correlation.
Ewing's sarcoma is an aggressive malignancy of bone and soft tissue with high incidence of metastasis and resistance to chemotherapy. Cytochrome P450 (CYP) monooxygenases are a family of enzymes that are involved in the metabolism of exogenous and endogenous compounds, including anti-cancer drugs, and have been implicated in the aggressive behaviour of various malignancies. Tumour samples and clinical information including age, sex, tumour site, tumour size, clinical stage and survival were collected from 36 adult and paediatric patients with Ewing's sarcoma family tumours. Tissue microarrays slides were processed for immunohistochemical labelling for CYP3A4, CYP3A5 and CYP3A7 using liver sections as positive control. The intensity of staining was scored as negative, low or high expression and was analysed statistically for any association with patients' clinical information. Four cases were later excluded due to inadequate viable tissue. CYP3A4 staining was present in 26 (81%) cases with high expression noted in 13 (40%) of 32 cases. High expression was significantly associated with distant metastases (P < 0.05). CYP3A5 and CYP3A7 were expressed in 5 and 13 cases respectively (15.6%, 40.6%). There was no association between the expression of CYP3A isoforms and age, sex, tumour size, or location (pelvic or extra-pelvic). None of the biomarkers showed any correlation with overall or disease-free survival. In conclusion, expression of CYP3A isoforms is noted in Ewing's sarcoma tumours and high CYP3A4 expression may be associated with metastasis. Additional studies are needed to further investigate the role of CYP3A4 in the prognosis of these tumours.


Rapid method for identification of gram-negative, nonfermentative bacilli.
A rapid system (OA), based on oxidative attack of substrates, was developed for identification of gram-negative, nonfermentative bacillia (NFB). One hundred and twelve strains of NFB from 25 species (representing the genera Pseudomonas, Alcaligenes, Acinetobacter, Bordetella, Flavobacterium, Moraxella, and Xanthomonas) were assayed by OA, buffered single substrate, and oxidative/fermentative methods. The 38 substrates consisted of salts of organic acids, nitrogen-containing compounds, alcohols, and carbohydrates. Ninety-four percent of the test strains were identified by the OA method in 24 h, and 99% were identifiable in 48 h. Reproducibility was 99%. Correlation with buffered single substrate was 98% (all substrates) and 90% with the oxidative/fermentative method (carbohydrates only). Biochemical profiles of all strains are presented, as well as tables showing the most useful tests for identification.


Oxidative stress on lens and cataract formation: role of light and oxygen.
The mechanism of oxidative damage to the lens through intraocular photochemical generation of superoxide and its derivatization to other oxidants such as singlet oxygen, hydroxyl radical and hydrogen peroxide has been studied. Rat lenses when organ cultured aerobically in TC 199 containing additional amounts of riboflavin were damaged as demonstrated by an inhibition of the uptake of Rb 86 against a concentration gradient. The pump was not affected by light if the culture was conducted in the basal TC 199. However, light was observed to induce significant peroxidative degradation of the tissue lipids even in the basal medium, the degradation being indicated by the formation of malonaldehyde. Both the inhibition of the pump as well as the peroxidative degradation of the tissue lipids, were attenuated considerably by scavengers of superoxide and hydrogen peroxide. In addition, the lipid degradation was prevented by vitamins C and E. The results suggest that the photodynamic injury to the lens cation pump as well as to membrane lipids is incumbent upon an initial generation of superoxide and its derivatization to other oxidants. Thus, the ocular lens is susceptible to oxidative insult and physiological damage through photocatalytic generation of various oxygen radicals. Large concentrations of ascorbic acid in the aqueous humor seems to be able to provide significant protection against such an insult. Thus, this may be one of the functions of high concentration of ascorbic acid in the aqueous humor. The implication of oxidative stress has also been examined in the genesis of cataracts in vivo. Treatment with vitamin E of the Emory mouse led to a decrease in the rate of cataract progression suggesting that at least in some instances an oxidative stress could participate in the formation of cataracts. Oxygen radicals may inflict damage at multifarious biochemical sites. Human lens lipids were also shown to have an absorption maxima at 239 nm indicating their susceptibility to oxidative degradation. In addition the lipid extract has fluorescence similar to that of lipofuscins. The levels of MDA were higher in the brunescent cataracts as compared to that in the nonbrunescent cataracts. The implications of oxidative stress towards the genesis of cataracts in humans is being explored further.


Immediate and long-term mental recovery from general versus epidural anesthesia in elderly patients.
The postoperative course of mental performance during the first week and at 3 months after operation was studied in 30 patients above the age of 60, undergoing total hip replacement arthroplasty. The patients were randomly allocated to receive either general anesthesia, epidural analgesia, or general anesthesia plus epidural analgesia. The surgically induced increase in plasma cortisol and glucose was inhibited in the two groups receiving epidural analgesia. Mental performance was studied with psychological methods. An equal degree of postoperative impairment of mental performance of 3-4 days' duration was found in all groups. Three months after surgery, mental function had improved slightly and to the same extent in all groups. We conclude that the after surgery, mental function had improved slightly and to the same extent in all groups. We conclude that the transient mental impairment occurring within the first postoperative week is caused by factors other than general anesthetic agents and the endocrine-metabolic response to surgery.


Carbonic anhydrase inhibition with natural products: novel chemotypes and inhibition mechanisms.
Five genetically distinct classes of carbonic anhydrases (CAs, EC 18.104.22.168) are present in organisms all over the phylogenetic tree (α-, β-, γ-, δ-, and ζ-families). These metalloenzymes catalyze CO(2) hydration to bicarbonate and protons. Inhibition of α-CAs from vertebrates, including humans, with sulfonamides was exploited clinically for decades for various classes of diuretics and systemically acting antiglaucoma agents, whereas newer inhibitors are used as topically acting antiglaucoma drugs, anticonvulsants, antiobesity, antipain and antitumor agents/diagnostic tools. Recently, novel interesting chemotypes, in addition to the sulfonamide and sulfamate were discovered, many of which are based on natural products, such as phenols/polyphenols, phenolic acids, and coumarins. Their detailed mechanism of inhibition has been explained by means of kinetic and X-ray crystallographic studies, and can be used for the rational drug design of other agents. Possible applications for these new chemotypes in drug design of CA inhibitors are envisaged and discussed in detail in this review.


Deterrents to nurses' participation in continuing professional development: an integrative literature review.
Continuing education (CE) helps nurses keep their practice safe and current. Although the literature provides information about motivating strategies, learning styles and settings, and reinforcement of the need to update skills, little research has focused on barriers to nurses' CE program attendance. This literature review describes factors that deter nurses' CE attendance. Ten research studies published between 1990 and 2008 addressing barriers to nurses' CE participation were located. The most frequent deterrents found were the cost of attending CE, inability to get time off from work to attend CE, and child care and home responsibilities. Leaders supporting CE must understand factors that motivate and prevent nurses from participating in CE. Implications from this study can assist educators to develop CE offerings to better meet staff needs and increase participation.


Lethal toxicity after administration of azacytidine: implication of the cytidine deaminase-deficiency syndrome.
Azacytidine, an antimetabolite with an original epigenetic mechanism of action, increases survival in patients diagnosed with high-risk myelodysplasic syndromes or acute myeloid leukemia with less than 30% medullar blasts. Azacytidine is a pyrimidine derivative that undergoes metabolic detoxification driven by cytidine deaminase (CDA), a liver enzyme whose gene is prone to genetic polymorphism, leading to erratic activity among patients. Clinical reports have shown that patients with the poor metabolizer (PM) phenotype are likely to experience early severe or lethal toxicities when treated with nucleosidic analogs such as gemcitabine or cytarabine. No clinical data have been available thus far on the relationships between CDA PM status and toxicities in azacytidine-treated patients. Here, we measured CDA activity in a case of severe toxicities with fatal outcome in a patient undergoing standard azacytidine treatment. Results showed that the patient was PM (i.e. residual activity reduced by 63%), thus suggesting that an impaired detoxification step could have given rise to the lethal toxicities observed. This case report calls for further prospective studies investigating the exact role that CDA status plays in the clinical outcome of patients treated with azacytidine.


[Effects of metabolic triad (25% polarizing solution, mildronat, preductal MR) in acute myocardial infarction].
The aim of the work was to study the effect of metabolic triad with different mechanisms of acting--high-dose Glucose-Insulin-Potassium--25% polarizing solution (25% glucose, 50 IU soluble insulin and 4% 144 ml KCL-GIK), mildronat, preductal MR on the functional condition of heart during the acute myocardial infarction. 20 patients from the main group and 20 from the control one have been under the study. Patients with diabetes and heavy forms of heart failure (killip class>2) were not included in the study. Evaluation of the functional condition of heart was based on ECG and echocardiography data received before and after the treatment. It was determined that the frequency of the rhythm disorder decreases in the conditions of metabolic triad as well as during the thrombolitic reperfusion. Average period of time for normalization of S-T segment elevation made up 5.4+/-1.8 days and 7.3+/-1.2 days in case of the control group. The received data make it relevant to include the complex metabolic triad for preventive purpose during the complications followed after the acute myocardial infarction.


On the tragedy of the commons: When predation and livestock loss may improve the economic lot of herders.
This paper studies the practice of semi-domestic reindeer (Rangifer t. tarandus) herding in Finnmark county in northern Norway. In this area, the Saami reindeer herders compete for space and grazing areas and keep large herds, while at the same time, the reindeer population is heavily exposed to carnivore predation by the lynx (Lynx lynx), the wolverine (Gulo gulo), and the golden eagle (Aquila chrysaetos). It is demonstrated that predation actually may improve the economic lot of livestock holders in this unmanaged local common setting. There are ecological as well as economic reasons as to why this happens. The ecological reason is that predation compensates for natural mortality; that is, increased predation reduces natural mortality, indicating that the net loss due to predation actually may be quite small. When predation reduces livestock density, the feeding conditions of the animals will improve, resulting in increased livestock weight and higher per animal slaughter value. At the same time, a smaller stock reduces the operating costs of the herders.


An assessment of the new "SCORE" index as a predictor of osteoporosis in women.
The study was done to determine whether the new SCORE (Simple Calculated Osteoporosis Risk Estimation) index might reduce the utilization of bone mineral density (BMD) measurement. 989 consecutive patients who were referred by a range of physicians for BMD assessments at one of two clinics had a SCORE index constructed. Approximately 95% of the subjects were Caucasian. The index is based on only 6 factors: age, previous fractures, rheumatoid arthritis, estrogen use, weight, and race. All but 1 (0.1%) of those with a femoral neck BMD T-score of < -2.5 had an abnormal SCORE index. However, its specificity was relatively low, since two thirds of those individuals also with an abnormal index had a T-score of > -2.5. One percent false negatives were also seen in the lumbar spine. The SCORE index correctly predicted those individuals who did not have an osteoporotic T-score. It was of the most value in the < 60 age group. The precise role of BMD measurement in the assessment and management of individuals possibly at risk for osteoporosis remains controversial. Our results suggest that the prior use of the SCORE index by the referring physicians to screen the patients sent for BMD measurement would have allowed them to exclude over 20% of the patients referred for assessment, and therefore reduce the need and cost of BMD measurement. The proportion of individuals who had a normal SCORE index, and would have been screened out, was 43% in the under 60 year age group, but in the 65 and over age group it provided no additional information to help with, for example, the National Osteoporosis Foundation (NOF) guidelines.


Statistical criteria for selecting the optimal number of untreated subjects matched to each treated subject when using many-to-one matching on the propensity score.
Propensity-score matching is increasingly being used to estimate the effects of treatments using observational data. In many-to-one (M:1) matching on the propensity score, M untreated subjects are matched to each treated subject using the propensity score. The authors used Monte Carlo simulations to examine the effect of the choice of M on the statistical performance of matched estimators. They considered matching 1-5 untreated subjects to each treated subject using both nearest-neighbor matching and caliper matching in 96 different scenarios. Increasing the number of untreated subjects matched to each treated subject tended to increase the bias in the estimated treatment effect; conversely, increasing the number of untreated subjects matched to each treated subject decreased the sampling variability of the estimated treatment effect. Using nearest-neighbor matching, the mean squared error of the estimated treatment effect was minimized in 67.7% of the scenarios when 1:1 matching was used. Using nearest-neighbor matching or caliper matching, the mean squared error was minimized in approximately 84% of the scenarios when, at most, 2 untreated subjects were matched to each treated subject. The authors recommend that, in most settings, researchers match either 1 or 2 untreated subjects to each treated subject when using propensity-score matching.


Microsaccade-rhythmic modulation of neural synchronization and coding within and across cortical areas V1 and V2.
Primates sample their visual environment actively through saccades and microsaccades (MSs). Saccadic eye movements not only modulate neural spike rates but might also affect temporal correlations (synchrony) among neurons. Neural synchrony plays a role in neural coding and modulates information transfer between cortical areas. The question arises of how eye movements shape neural synchrony within and across cortical areas and how it affects visual processing. Through local field recordings in macaque early visual cortex while monitoring eye position and through neural network simulations, we find 2 distinct synchrony regimes in early visual cortex that are embedded in a 3- to 4-Hz MS-related rhythm during visual fixation. In the period shortly after an MS ("transient period"), synchrony was high within and between cortical areas. In the subsequent period ("sustained period"), overall synchrony dropped and became selective to stimulus properties. Only mutually connected neurons with similar stimulus responses exhibited sustained narrow-band gamma synchrony (25-80 Hz), both within and across cortical areas. Recordings in macaque V1 and V2 matched the model predictions. Furthermore, our modeling provides predictions on how (micro)saccade-modulated gamma synchrony in V1 shapes V2 receptive fields (RFs). We suggest that the rhythmic alternation between synchronization regimes represents a basic repeating sampling strategy of the visual system.


Overproduction of Neurons Is Correlated with Enhanced Cortical Ensembles and Increased Perceptual Discrimination.
Brains vary greatly in neuronal number and density, even across individuals within the same species, yet it remains unclear whether such variation leads to differences in brain function or behavior. By imaging cortical activity of a mouse model in which neuronal production is moderately enhanced in utero, we find that animals with more cortical neurons also develop enhanced functional correlations and more distinct neuronal ensembles in primary visual cortex. These mice also have sharper orientation discrimination in their visual behavior. These results unveil a correlation between neuronal ensembles and behavior and suggest that neuronal number is linked to functional modularity and perceptual discrimination of visual cortex. By experimentally linking differences in neuronal number and behavior, our findings could help explain how evolutionary and developmental variability of individual and species brain size may lead to perceptual and cognitive differences.


Role of Nutrients and Phyto-compounds in the Modulation of Antimicrobial Resistance.
Antimicrobial resistance is quickly spreading and has become a major public health problem worldwide. If this issue is not resolved, it may cause a shift back to the pre-antibiotics era and infectious disease will again be a serious problem, especially in developing countries. Since the discovery of antibiotics, bacterial resistance has emerged, enabling certain bacteria to withstand antibiotic action. The emergence of antibiotic resistance is fueled by excessive and improper use of antimicrobial agents, especially in developing countries. For this reason, alternatives to or modifications of current treatment methods have been sought. The aim of this review is to highlight the possible synergies of various agents that can augment antibiotic activities. A structured literature search was conducted using only papers that have been published in PubMed with the focus on the agents that are likely to modulate antimicrobial resistance. In this review, data was retrieved from the literature regarding the possible synergies that exist between commercially available antimicrobial drugs with agents of interest. The papers included were summarized and analyzed, critiqued and compared for their contents using a conceptual frame-work. In total, one hundred and twenty six papers were reviewed. The number of papers that dealt with the different topics included are as follows (): emergence of antimicrobial resistance (22), bioactive phyto-compounds (36) (phytobiologics, and phytochemicals), Antioxidants (40) (N-acetylcysteine, Ambroxol, Ascorbic acid, Glutathione and vitamin E), Peptide synergies (14) (Synthetic cationic α-helical AMPs, CopA3, Alafosfalin, PMAP-36, Phosphonopeptide L-norvalyl-L-1-aminoethylphosphonic acid and norcardicin-A), nano-antibiotics (10), drug-compound interactions (4).This review addressed the new strategies using the above compounds in the modulation of antimicrobial resistance to avoid issues related to resistance of bacteria to antibiotics. The findings of this review confirm that certain compounds can act in synergy with currently used antimicrobials to enhance the potential of antimicrobial agents and thus to reduce the emergence of antimicrobial resistance. Some of these synergies are already being used to enhance the potential of currently used antimicrobial agents. More studies need to be conducted to better understand the mechanism of action of such compounds, and based on the results, new compounds may be sought.


Coevolution of cyclin Pcl5 and its substrate Gcn4.
Gcn4, a transcription factor that plays a key role in the response of Saccharomyces cerevisiae to amino acid starvation, is regulated at both the levels of translation and of protein stability. Regulated degradation of Gcn4 depends on its phosphorylation by the cyclin-dependent kinase Pho85, in conjunction with the cyclin Pcl5. The pathogenic yeast Candida albicans contains a functional homolog of Gcn4, which is involved in amino acid metabolism, as well as in the regulation of filamentous growth in response to starvation. Here, we show that C. albicans Gcn4 (CaGcn4) is rapidly degraded and that this degradation depends on a Pho85 cyclin homolog, CaPcl5. The regulatory loop that includes Gcn4 and Pcl5 is conserved in C. albicans: like in S. cerevisiae, CaPcl5 is transcriptionally induced by CaGcn4 and is required for CaGcn4 degradation. However, the proteins have coevolved so that there is no cross-recognition between the proteins from the two species: phosphorylation-dependent degradation of CaGcn4 occurs only in the presence of CaPcl5, and S. cerevisiae Gcn4 (ScGcn4) requires ScPcl5 for its degradation. Phenotypic analysis of the Capcl5 mutant indicates that CaPcl5 also modulates the filamentous response of C. albicans in amino acid-rich media.