Draxin, a repulsive guidance protein for spinal cord and forebrain commissures.
Axon guidance proteins are critical for the correct wiring of the nervous system during development. Several axon guidance cues and their family members have been well characterized. More unidentified axon guidance cues are assumed to participate in the formation of the extremely complex nervous system. We identified a secreted protein, draxin, that shares no homology with known guidance cues. Draxin inhibited or repelled neurite outgrowth from dorsal spinal cord and cortical explants in vitro. Ectopically expressed draxin inhibited growth or caused misrouting of chick spinal cord commissural axons in vivo. draxin knockout mice showed defasciculation of spinal cord commissural axons and absence of all forebrain commissures. Thus, draxin is a previously unknown chemorepulsive axon guidance molecule required for the development of spinal cord and forebrain commissures.


Lack of efficacy of mefloquine in the treatment of New World cutaneous leishmaniasis in Colombia.
In a nonblinded, therapeutic trial conducted in Colombia, 1.25-1.5 grams of mefloquine base given as a single oral dose or as 250 mg a day for 5-6 consecutive days was not efficacious in the treatment of New World cutaneous leishmaniasis. The drug had cured only 30.8 % of patients with leishmaniasis skin lesions by the 10th week after start of therapy as compared with a 27.9% complete cicatrization rate in historical controls treated with placebo tablets and an 86.3% cicatrization rate in historical controls who received meglumine antimoniate, 20 mg/ kg/day intramuscularly for 20 days, with no upper limit to daily dose. It is concluded that a single course treatment with mefloquine is not indicated as monotherapy in the treatment of Colombian cutaneous leishmaniasis primarily due to L. panamensis.


CD23 (the low-affinity IgE receptor) as a C-type lectin: a multidomain and multifunctional molecule.
This review, regards the low-affinity receptor CD23 as a C-type lectin and compares it with other C-type lectins and C-type lectin-like receptors. C-type lectins such as the asialoglycoprotein receptor, as well as the dendritic cell immunoreceptor and the dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin on dendritic cell lectin, possess amino acid sequences which interact with Ca++ and sugar, and many of them possess an endocytosis signal sequence that includes tyrosine or serine in the cytoplasmic region. In contrast, natural killer receptors lack the Ca++ and sugar-binding amino acids but conserve homologous cysteines in the form of C-type lectin, and possess an immunoreceptor tyrosine-based inhibitory motif in the cytoplasmic region which inhibits killer activity when they recognize the self major histocompatibility (MHC) class I molecule. Since human CD23a form has a similar amino acid sequence, the possibility that this sequence is an endocytosis signal or an ITIM is discussed. The function of the reverse RGD and RGD-binding inhibitory peptide in human CD23 from the point of view of the relation between a C-type lectin and MHC class II molecules is also considered.


Inhibition of starch digestion by alpha-amylase inhibitor reduces the efficiency of utilization of dietary proteins and lipids and retards the growth of rats.
Digestion/absorption and nutritional utilization of starch, protein and lipids were studied in rats fed diets containing purified kidney bean alpha-amylase inhibitor at levels of 0, 1.6, 3.3 and 6.6 g/kg diet. At the two higher levels, the growth rate of rats and the apparent digestibilities and utilization of dietary starch and protein were significantly less than in control rats, and losses of nitrogen, lipids and carbohydrate resulted in a significant reduction in dry body weight. Some organs of the body were also affected: the relative dry weights of the intestines and the pancreas were higher, whereas liver and thymus weights were lower than in control rats. As starch digestion in the small intestine was negligible at higher inhibitor concentrations, the cecum was practically blocked by solidified digesta. This effect and the ensuing bacterial fermentation stimulated the growth of this tissue by hyperplasia and hypertrophy. However, as the distension was not always sufficient, the organ was occasionally ruptured and the rats had to be killed. Inhibitor doses in this work were comparable to those in clinical studies, implying that the use of the inhibitor is not without health risks. Moreover, diets rich in alpha-amylase inhibitor such as those containing transgenic plants with high levels of inhibitor gene expression cannot be recommended in intensive animal production.


Impact of resolvin E1 on murine neutrophil phagocytosis in type 2 diabetes.
Diabetic complications involve inflammation-mediated microvascular and macrovascular damage, disruption of lipid metabolism, glycosylation of proteins, and abnormalities of neutrophil-mediated events. Resolution of inflamed tissues to health and homeostasis is an active process mediated by endogenous lipid agonists, including lipoxins and resolvins. This proresolution system appears to be compromised in type 2 diabetes (T2D). The goal of this study was to investigate unresolved inflammation in T2D. Wild-type (WT) and genetically engineered mice, including T2D mice (db/db), transgenic mice overexpressing the human resolvin E1 (RvE1) receptor (ERV1), and a newly bred strain of db/ERV1 mice, were used to determine the impact of RvE1 on the phagocytosis of Porphyromonas gingivalis in T2D. Neutrophils were isolated and incubated with fluorescein isothiocyanate-labeled P. gingivalis, and phagocytosis was measured in a fluorochrome-based assay by flow cytometry. Mitogen-activated protein kinase (MAPK) (p42 and p44) and Akt (Thr308 and Ser473) phosphorylation was analyzed by Western blotting. The mouse dorsal air pouch model was used to evaluate the in vivo impact of RvE1. Results revealed that RvE1 increased the neutrophil phagocytosis of P. gingivalis in WT animals but had no impact in db/db animals. In ERV1-transgenic and ERV1-transgenic diabetic mice, phagocytosis was significantly increased. RvE1 decreased Akt and MAPK phosphorylation in the transgenic animals. In vivo dorsal air pouch studies revealed that RvE1 decreases neutrophil influx into the pouch and increases neutrophil phagocytosis of P. gingivalis in the transgenic animals; cutaneous fat deposition was reduced, as was macrophage infiltration. The results suggest that RvE1 rescues impaired neutrophil phagocytosis in obese T2D mice overexpressing ERV1.


Doctor's assistants--do we need them?
To investigate the potential for the doctor's assistant role within an accident and emergency (A&E) department in relation to consultant workload. A time and motion evaluation of the activities of four A&E consultants before and after a doctor's assistant was established as a team member within our department. A review of the literature was undertaken to allow comparisons with the American model of the physician assistant within the emergency department. The initial evaluation indicated that over 20% of the consultant's time could have been saved if an assistant were available to perform a variety of non-medical tasks. The restudy performed once the assistant was in post indicated less time was spent by the doctors in "medical" clerical duties (6.7% v 11.5% time), telephone use (5.6% v 7.7%), and venepuncture/cannula insertion (0.4% v 2.1%), and more time was spent on consultation over cases (15.3% v 11.3%) and supervision of other staff (9.3% v 4.1%). These five areas changed significantly (p = 0.005 by paired t test). The doctor's assistant may have a role in reprofiling the workload of senior doctors in A&E departments in the UK. They may also have a role in reducing the pressure on junior doctors, though this effect was not evaluated.


Creating opportunities to support oncology nursing practice: surviving and thriving.
There is a growing body of evidence to support that specialization in nursing leads to improved outcomes for patients, including increased QOL, improved symptom management, and fewer hospital admissions. Oncology nurses face several challenges in pursuing specialization, due to individual and system issues such as limited time and resources. To address these challenges, de Souza Institute launched a province-wide study group for nurses in Ontario who planned to write the Canadian Nurses Association (CNA) Oncology Certification Exam. The study group was led by educators from de Souza and Princess Margaret Hospital and drew expertise from nursing leaders across Ontario who shared the same vision of oncology nursing excellence. The study group was innovative by embracing telemedicine and web-based technology, which enabled flexibility for nurses' work schedules, learning styles, physical location and practice experience. The study group utilized several theoretical perspectives and frameworks to guide the curriculum: Adult Learning Theories, Cooperative Learning, Generational Learning Styles, CANO standards for practice and the CNA exam competencies. This approach enabled 107 oncology nurses across the province in 17 different sites to connect, as a group, study interactively and fully engage in their learning. A detailed evaluation method was utilized to assess baseline knowledge, learning needs, cooperative group process, exam success rates, and document unexpected outcomes. Ninety-four per cent of participants passed the CNA Oncology Exam. Lessons learned and future implications are discussed. The commitment remains to enable thriving through generating new possibilities, building communities of practice, mentoring nurses and fostering excellence in oncology practice.


A family systems nursing intervention model for paediatric health crisis.
This article discusses the development of a family systems nursing intervention for clinical use in health crisis. Although studies in paediatric critical care provide evidence that family stress is an important clinical phenomenon, studies have demonstrated that few nurses have the requisite family intervention skills to provide family members with adequate support during crisis. In addition, few intervention studies that focus on provider-family relationships with the goal of reducing stress have been reported. This article contributes to the literature by redressing this lack. Data sources. The literature search supporting this project spanned from 1980 to 2009 and included searches from classic nursing theory, family theory and relevant nursing research specific to the design of the intervention reported. The goal of the intervention is to provide a theoretical and practical foundation for explicit action that enhances relationships with caregivers thereby supporting the integrity of the family and enhancing their coping abilities. The intervention, based on the Family Systems Model and the family's understandings of the situation, defines specific goals and desired outcomes to guide strategic actions. Discussion of the conceptual foundation, procedural development and an example of the protocol is provided. Implications for nursing. The intervention is designed for nurses with limited knowledge in family theory to aid them to better help families dealing with stress. The proposed intervention can be used to increase nurses' skills in family centred nursing care. Although designed for use in paediatric critical care, it can, with modifications, be used in other nursing specialty areas.


Promoting Nurse Retention Through Career Development Planning.
This is the second article in a new series about evidence-based practice (EBP) that builds on AJN's award-winning previous series-Evidence-Based Practice, Step by Step-published between 2009 and 2011 (to access the series, go to http://links.lww.com/AJN/A133). This follow-up series will feature exemplars illustrating the various strategies that can be used to implement EBP changes-one of the most challenging steps in the EBP process.


Hedgehog-Interacting Protein is a multimodal antagonist of Hedgehog signalling.
Hedgehog (HH) morphogen signalling, crucial for cell growth and tissue patterning in animals, is initiated by the binding of dually lipidated HH ligands to cell surface receptors. Hedgehog-Interacting Protein (HHIP), the only reported secreted inhibitor of Sonic Hedgehog (SHH) signalling, binds directly to SHH with high nanomolar affinity, sequestering SHH. Here, we report the structure of the HHIP N-terminal domain (HHIP-N) in complex with a glycosaminoglycan (GAG). HHIP-N displays a unique bipartite fold with a GAG-binding domain alongside a Cysteine Rich Domain (CRD). We show that HHIP-N is required to convey full HHIP inhibitory function, likely by interacting with the cholesterol moiety covalently linked to HH ligands, thereby preventing this SHH-attached cholesterol from binding to the HH receptor Patched (PTCH1). We also present the structure of the HHIP C-terminal domain in complex with the GAG heparin. Heparin can bind to both HHIP-N and HHIP-C, thereby inducing clustering at the cell surface and generating a high-avidity platform for SHH sequestration and inhibition. Our data suggest a multimodal mechanism, in which HHIP can bind two specific sites on the SHH morphogen, alongside multiple GAG interactions, to inhibit SHH signalling.


First principles investigation on elastic, optoelectronic and thermoelectric properties of KYX (X = Ge, Sn and Pb) half-heusler compounds.
Theoretical calculations based on the density functional theory and the Boltzmann semi-classical transport theory have been carried out to examine the structural, elastic, electronic, optical and thermoelectric properties of Potassium- and Yttrium-based half-Heusler (HH) compounds KYX (X = Ge, Sn and Pb). Based on our calculations, KYGe, KYSn, and KYPb HH compounds are mechanically stable, and show semiconductor nature with direct band gaps of 0.852, 0.921, and 0.927 eV, respectively, which are obtained from mBJ level of theory. Moreover, the KYSn is brittle, while the KYGe and KYPb are dutile. The optical results show that these HH compounds have wide absorption band from high energy region of infrarred to ultraviolet region. At high photon energies (beyond of 13 eV), they shows very small reflectivity. Because of their favorable electronic structure, these materials have very good thermoelectric performance with high thermopower and figure of merit. The effect of temperature on thermoelectric properties also is discussed in details.


Quantifying Vocal Power: Correlation of Whole-Body Anaerobic Power to Vocal Function Measures.
Purpose The purpose of this preliminary study was to identify a vocal task that could be used as a clinical indicator of the vocal aptitude or vocal fitness required for vocally demanding occupations in a manner similar to that of the anaerobic power tests commonly used in exercise science. Performance outcomes for vocal tasks that require rapid acceleration and high force production may be useful as an indirect indicator of muscle fiber complement and bioenergetic fitness of the larynx, an organ that is difficult to study directly. Method Sixteen women (age range: 19-24 years, M age = 22 years) were consented for participation and completed the following performance measures: forced vital capacity, three adapted vocal function tasks, and the horizontal sprint test. Results Using a within-participant correlational analyses, results indicated a positive relationship between the rate of the last second of a laryngeal diadochokinesis task that was produced at a high fundamental frequency/high sound level and anaerobic power. Forced vital capacity was not correlated with any of the vocal function tasks. Conclusions These preliminary results indicate that aspects of the laryngeal diadochokinesis task produced at a high fundamental frequency and high sound level may be useful as an ecologically valid measure of vocal power ability. Quantification of vocal power ability may be useful as a vocal fitness assessment or as an outcome measure for voice rehabilitation and habilitation for patients with vocally demanding jobs.


Carbimazole is an inhibitor of protein synthesis and protects from neuronal hypoxic damage in vitro.
Oxygen deprivation during ischemic or hemorrhagic stroke results in ATP depletion, loss of ion homeostasis, membrane depolarization, and excitotoxicity. Pharmacologic restoration of cellular energy supply may offer a promising concept to reduce hypoxic cell injury. In this study, we investigated whether carbimazole, a thionamide used to treat hyperthyroidism, reduces neuronal cell damage in oxygen-deprived human SK-N-SH cells or primary cortical neurons. Our results revealed that carbimazole induces an inhibitory phosphorylation of eukaryotic elongation factor 2 (eEF2) that was associated with a marked inhibition of global protein synthesis. Translational inhibition resulted in significant bioenergetic savings, preserving intracellular ATP content in oxygen-deprived neuronal cells and diminishing hypoxic cellular damage. Phosphorylation of eEF2 was mediated by AMP-activated protein kinase and eEF2 kinase. Carbimazole also induced a moderate calcium influx and a transient cAMP increase. To test whether translational inhibition generally diminishes hypoxic cell damage when ATP availability is limiting, the translational repressors cycloheximide and anisomycin were used. Cycloheximide and anisomycin also preserved ATP content in hypoxic SK-N-SH cells and significantly reduced hypoxic neuronal cell damage. Taken together, these data support a causal relation between the pharmacologic inhibition of global protein synthesis and efficient protection of neurons from ischemic damage by preservation of high-energy metabolites in oxygen-deprived cells. Furthermore, our results indicate that carbimazole or other translational inhibitors may be interesting candidates for the development of new organ-protective compounds. Their chemical structure may be used for computer-assisted drug design or screening of compounds to find new agents with the potential to diminish neuronal damage under ATP-limited conditions.


The Avr (effector) proteins HrmA (HopPsyA) and AvrPto are secreted in culture from Pseudomonas syringae pathovars via the Hrp (type III) protein secretion system in a temperature- and pH-sensitive manner.
We present here data showing that the Avr proteins HrmA and AvrPto are secreted in culture via the native Hrp pathways from Pseudomonas syringae pathovars that produce these proteins. Moreover, their secretion is strongly affected by the temperature and pH of the culture medium. Both HrmA and AvrPto were secreted at their highest amounts when the temperature was between 18 and 22 degrees C and when the culture medium was pH 6.0. In contrast, temperature did not affect the secretion of HrpZ. pH did affect HrpZ secretion, but not as strongly as it affected the secretion of HrmA. This finding suggests that there are at least two classes of proteins that travel the P. syringae pathway: putative secretion system accessory proteins, such as HrpZ, which are readily secreted in culture; and effector proteins, such as HrmA and AvrPto, which apparently are delivered inside plant cells and are detected in lower amounts in culture supernatants under the appropriate conditions. Because HrmA was shown to be a Hrp-secreted protein, we have changed the name of hrmA to hopPsyA to reflect that it encodes a Hrp outer protein from P. syringae pv. syringae. The functional P. syringae Hrp cluster encoded by cosmid pHIR11 conferred upon P. fluorescens but not Escherichia coli the ability to secrete HopPsyA in culture. The use of these optimized conditions should facilitate the identification of additional proteins traveling the Hrp pathway and the signals that regulate this protein traffic.


Damping capacity is evolutionarily conserved in the radial silk of orb-weaving spiders.
Orb-weaving spiders depend upon their two-dimensional silk traps to stop insects in mid flight. While the silks used to construct orb webs must be extremely tough to absorb the tremendous kinetic energy of insect prey, webs must also minimize the return of that energy to prey to prevent insects from bouncing out of oscillating webs. We therefore predict that the damping capacity of major ampullate spider silk, which forms the supporting frames and radial threads of orb webs, should be evolutionarily conserved among orb-weaving spiders. We test this prediction by comparing silk from six diverse species of orb spiders. Silk was taken directly from the radii of orb webs and a Nano Bionix test system was used either to sequentially extend the silk to 25% strain in 5% increments while relaxing it fully between each cycle, or to pull virgin silk samples to 15% strain. Damping capacity was then calculated as the percent difference in loading and unloading energies. Damping capacity increased after yield for all species and typically ranged from 40 to 50% within each cycle for sequentially pulled silk and from 50 to 70% for virgin samples. Lower damping at smaller strains may allow orb webs to withstand minor perturbations from wind and small prey while still retaining the ability to capture large insects. The similarity in damping capacity of silk from the radii spun by diverse spiders highlights the importance of energy absorption by silk for orb-weaving spiders.


Synthesis and pre-clinical evaluation of a new class of high-affinity 18F-labeled PSMA ligands for detection of prostate cancer by PET imaging.
Current clinical imaging of PSMA-positive prostate cancer by positron emission tomography (PET) mainly features 68Ga-labeled tracers, notably [68Ga]Ga-PSMA-HBED-CC. The longer half-life of fluorine-18 offers significant advantages over Ga-68, clinically and logistically. We aimed to develop high-affinity PSMA inhibitors labeled with fluorine-18 as alternative tracers for prostate cancer. Six triazolylphenyl ureas and their alkyne precursors were synthesized from the Glu-urea-Lys PSMA binding moiety. PSMA affinity was determined in a competitive binding assay using LNCaP cells. The [18F]triazoles were isolated following a Cu(I)-catalyzed click reaction between the alkynes and [18F]fluoroethylazide. The 18F-labeled compounds were evaluated in nude mice bearing LNCaP tumors and compared to [68Ga]Ga-PSMA-HBED-CC and [18F]DCFPyL. Biodistribution studies of the two tracers with the highest imaged-derived tumor uptake and highest PSMA affinity were undertaken at 1 h, 2 h and 4 h post-injection (p.i.), and co-administration of PMPA was used to determine whether uptake was PSMA-specific. F-18-labeled triazolylphenyl ureas were prepared with a decay-corrected RCY of 20-40 %, >98 % radiochemical and chemical purity, and specific activity of up to 391 GBq/μmol. PSMA binding (IC50) ranged from 3-36 nM. The position of the triazole influenced tumor uptake (3 > 4 > 2), and direct conjugation of the triazole with the phenylurea moiety was preferred to insertion of a spacer group. Image-derived tumor uptake ranged from 6-14 %ID/g at 2 h p.i., the time of maximum tumor uptake; uptake of [68Ga]Ga-PSMA-HBED-CC and [18F]DCFPyL was 5-6 %ID/g at 1-3 h p.i., the time of maximum tumor uptake. Biodistribution studies of the two most promising compounds gave maximum tumor uptakes of 10.9 ± 1.0 % and 14.3 ± 2.5 %ID/g, respectively, as compared to 6.27 ± 1.44 %ID/g for [68Ga]Ga-PSMA-HBED-CC. Six [18F]triazolylphenyl ureas were prepared in good radiochemical yield. Compounds showed PSMA-specific uptake in LNCaP tumors as high as 14 % ID/g, more than a 2-fold increase over [68Ga]Ga-PSMA-HBED-CC. The facile and high-yielding radiosynthesis of these 18F-labeled triazoles as well as their promising in vitro and in vivo characteristics make them worthy of clinical development for PET imaging of prostate cancer.


Effects of Plyometric Training on Neuromuscular Performance in Youth Basketball Players: A Pilot Study on the Influence of Drill Randomization.
The aim of this single-blind randomized controlled trial was to compare the effects of plyometric jump training (PJT), with (RG) and without (NRG) between-session drill randomization, on performance measures (i.e., jumping and sprinting abilities, change of direction speed, and technical performance) in youth male basketball players (age, 10.2 ± 1.7 years), assigned to either the NRG (n = 7), RG (n = 6), or control group (n = 6). Before and after the intervention, countermovement jump, 20-cm drop jump, 30-m sprint (with or without ball dribbling), and change-of-direction speed tests were completed. The PJT was applied twice per week for seven weeks. The only difference between PJT groups was the order of drill execution. An ANOVA was used to detect differences between study groups. The analyses revealed significant main effects of time (all p<.01; d = 0.64-0.89) and group x time interaction (all p<.05; d=0.31-51) for all examined variables. Post hoc analyses revealed moderate-large significant improvements for the RG (countermovement jump: 18.8%, d = 0.6; 20-cm drop jump: 23.9%, d = 0.80; 30-m sprint: 11.6%, d = 1.13; 30-m sprint with ball dribbling: 9.3%, d = 0.54; change of direction speed test: 14.6%, d = 1.82). In contrast, post hoc analyses revealed only small improvements for the NRG (20-cm drop jump: 14.1%, d = 0.36; 30-m sprint: 6.8%, d = 0.45; 30-m sprint with ball dribbling: 8.8%, d = 0.35; change of direction speed test: 10.5%, d = 0.49). Application of PJT without randomization is effective for improving physical and technical qualities. However, PJT could be more beneficial when executed with between-session randomization of drills.


Generalized choriocapillaris dystrophy, a distinct phenotype in the spectrum of ABCA4-associated retinopathies.
We describe a particular form of autosomal recessive generalized choriocapillaris dystrophy phenotype associated with ABCA4 mutations. A cohort of 30 patients with identified ABCA4 mutations and a distinct phenotype was studied. A retrospective review of history, fundus photographs, electroretinography, visual field testing, dark adaptometry, and optical coherence tomography was performed. Genetic analyses were performed by ABCA4 microarray analysis, high resolution melting, and/or next generation sequencing of all protein-coding sequences of the ABCA4 gene. The earliest recorded manifestation of ABCA4-associated disease was a central bull's eye type of macular dystrophy that progressed to chorioretinal atrophy of the macula with coarse rounded hyperpigmentations and expanding involvement of the periphery. The mean age at first presentation was 10.3 years, the longest follow-up was 61 years. All patients had two ABCA4 mutations identified, confirming the molecular genetic diagnosis of an ABCA4-associated disease. Most patients harbored at least one mutation classified as "severe," the most common of which was the p.N965S variant that had been found previously at a high frequency among patients with ABCA4-associated retinal dystrophies in Denmark. Generalized choriocapillaris dystrophy is a progressive ABCA4-associated phenotype characterized by early-onset macular dystrophy that disperses and expands to widespread end-stage chorioretinal atrophy with profound visual loss. All cases in this study were confirmed as harboring two ABCA4 mutations. Most of the ABCA4 mutations were classified as "severe" explaining the early onset, panretinal degeneration, and fast progression of the disease.


Detection of Matrilysin Activity Using Polypeptide Functionalized Reduced Graphene Oxide Field-Effect Transistor Sensor.
A novel approach for rapid and sensitive detection of matrilysin (MMP-7, a biomarker involved in the degradation of various macromolecules) based on a polypeptide (JR2EC) functionalized reduced graphene oxide (rGO) field effect transistor (FET) is reported. MMP-7 specifically digests negatively charged JR2EC immobilized on rGO, thereby modulating the conductance of rGO-FET. The proposed assay enabled detection of MMP-7 at clinically relevant concentrations with a limit of detection (LOD) of 10 ng/mL (400 pM), attributed to the significant reduction of the net charge of JR2EC upon digestion by MMP-7. Quantitative detection of MMP-7 in human plasma was further demonstrated with a LOD of 40 ng/mL, illustrating the potential for the proposed methodology for tumor detection and carcinoma diagnostic (e.g., lung cancer and salivary gland cancer). Additionally, excellent specificity of the proposed assay was demonstrated using matrix metallopeptidase 1 (MMP-1), a protease of the same family. With appropriate selection and modification of polypeptides, the proposed assay could be extended for detection of other enzymes with polypeptide digestion capability.


Circumcision ceremonies at the Ottoman palace.
Circumcision is widely practiced in all Islamic countries. Festivities pertaining to circumcision vary according to the regions and civilizations. In this report, circumcision festivities at the Ottoman Palace and the socioeconomic importance of the tradition are presented. The Ottoman circumcision technique is discussed, as are the miniature paintings, in manuscript, written on the occasion of the circumcision of the sons of the Sultans. Because these festivities involved the participation of all classes of the society and all professions they contributed to social and technical progress and led to developments in art, music, sports, and ideas.


A layered wide-gap oxyhalide semiconductor with an infinite ZnO2 square planar sheet: Sr2ZnO2Cl2.
A new square-planar zinc oxyhalide, Sr2ZnO2Cl2, was successfully synthesized using a high-pressure method. Absorption spectroscopy revealed an indirect band gap of 3.66 eV. Electronic structure calculations indicated a strong hybridization between Zn 3dx2-y2 and O 2p orbitals, which is distinct from tetrahedrally coordinated ZnO.


Cloning and expression of a Leishmania donovani gene instructed by a peptide isolated from major histocompatibility complex class II molecules of infected macrophages.
The studies reported here describe the isolation of peptides from MHC class II molecules of murine macrophages infected with Leishmania donovani, and the use of the derived peptide sequences to rescue the pathogen peptide donor protein. The isolation of the peptides was carried out by comparing the RP HPLC profile of peptides extracted from infected macrophages with the peptides extracted from noninfected cells. Several distinct HPLC peaks unique to infected macrophages were sequenced. One of the peptides that was not homologous to any known protein was used to instruct the designing of an oligonucleotide sense primer that was used in combination with an oligo dT nucleotide (anti-sense primer) to amplify by PCR a DNA fragment from L. donovani cDNA. The amplified DNA fragment was cloned and used as a probe to screen a L. donovani cDNA library. The cloned gene (Ld peptide gene) has an open reading frame of 525 bp and has no homology with any known protein/gene sequence. Northern blot analyses indicated that the Ld peptide/gene is broadly distributed and expressed among species of the Leishmania genus, in both the amastigote and promastigote life cycle forms. Using the pGEX 2T vector, the gene was expressed and the relationship of the purified recombinant protein with L. donovani was confirmed using both antibody and T cell responses from immunized or infected animals. The gene encodes a 23-kD molecule (Ldp 23) associated with the cell surface of L. donovani promastigotes. In addition, T cells purified from the lymph nodes of BALB/c mice immunized with L. donovani or infected with L. major, and from CBA/J mice infected with L. amazonensis were stimulated to proliferate by the recombinant Ldp 23 and produced high levels of IFN-gamma and no IL 4. This observation suggests that the Ldp 23 is an interesting parasite molecule for the studies concerning the host/parasite interaction because the Th1 pattern of cytokine response that it induces is correlated with resistance to Leishmania infections. These results clearly point to an alternative strategy for the purification of proteins useful for the development of both vaccines and immunological diagnostic tools not only against leishmaniasis but also for other diseases caused by intracellular pathogens.


Quality of HIV care provided by non-physician clinicians and physicians in Mozambique: a retrospective cohort study.
To compare HIV care quality provided by non-physician clinicians (NPC) and physicians. Retrospective cohort study assessing the relationship between provider cadre and HIV care quality among non-pregnant adult patients initiating antiretroviral therapy (ART) in the national HIV care programme. Computerized medical records from patients initiating ART between July 2004 and October 2007 at two HIV public HIV clinics in central Mozambique were used to develop multivariate analyses evaluating differences in process and care continuity measures for patients whose initial provider was a NPC or physician. A total of 5892 patients was included in the study, including 4093 (69.5%) with NPC and 1799 (30.5%) with physicians as initial providers. Those whose initial provider was a NPC were more likely to have a CD4 cell count 90-210 days [risk ratio (RR) 1.13, 1.04<RR<1.23] and 330-390 days (RR 1.12, 0.96<RR<1.31) after initiating ART. A large majority of patients adhered well to care, although patients whose initial provider was a NPC had more frequent clinical visits in the first year post-ART initiation (RR 1.02, 1.00<RR<1.05) and higher levels of adherence to antiretroviral medicines in the first 6 months after initiating ART (RR1.05, 1.02<RR<1.09). Patients of NPC were less likely to be lost to follow-up than those seen by physicians (RR 0.86, 0.73<RR<1.02). NPC performance was similar to or better than that of physicians for the HIV care quality study measures. Our results highlight the important role of NPC in scaling up ART in Mozambique, and argue for using all relevant clinical resources to meet the large demands for care in countries with high HIV burdens.


Early Functional and Morphologic Abnormalities in the Diabetic Nyxnob Mouse Retina.
The electroretinogram c-wave is generated by the summation of the positive polarity hyperpolarization of the apical RPE membrane and a negative polarity slow PIII response of Müller glia cells. Therefore, the c-wave reduction noted in prior studies of mouse models of diabetes could reflect a reduction in the RPE component or an increase in slow PIII. The present study used a genetic approach to distinguish between these two alternatives. Nyxnob mice lack the ERG b-wave, revealing the early phase of slow PIII. To visualize changes in slow PIII due to diabetes, Nyxnob mice were given streptozotocin (STZ) injections to induce diabetes or received vehicle as a control. After 1, 2, and 4 weeks of sustained hyperglycemia (>250 mg/dL), standard strobe flash ERG and dc-ERG testing were conducted. Histological analysis of the retina was performed. A reduced c-wave was noted at the 1 week time point, and persisted at later time points. In comparison, slow PIII amplitudes were unaffected after 1 week of hyperglycemia, but were significantly reduced in STZ mice at the 2-week time point. The decrease in amplitude occurred before any identifiable decrease to the a-wave. At the later time point, the a-wave became involved, although the slow PIII reductions were more pronounced. Morphological abnormalities in the RPE, including increased thickness and altered melanosome distribution, were identified in diabetic animals. Because the c-wave and slow PIII were both reduced, these results demonstrated that diabetes-induced reductions to the c-wave cannot be attributed to an early increase in the Müller glia-derived potassium conductance. Furthermore, because the a-wave, slow PIII and c-wave reductions were not equivalent, and varied in their onset, the reductions cannot reflect the same mechanism, such as a change in membrane resistance. The presence of small changes to RPE architecture indicate that the c-wave reductions present in diabetic mice likely represents a primary change in the RPE induced by hyperglycemia.


Opioid receptors are coupled tightly to G proteins but loosely to adenylate cyclase in NG108-15 cell membranes.
Opioid receptors in intact NG 108-15 cells were irreversibly inactivated with increasing concentrations of the alkylating antagonist beta-chlornaltrexamine (CNA). The consequence of the reduction in density of opioid binding sites (quantified by saturation analysis of opioid binding in membranes) was studied at two steps of opioid receptor-mediated responses, (a) stimulation of high affinity GTPase and (b) inhibition of basal adenylate cyclase. Both agonist-mediated stimulation of GTPase and inhibition of adenylate cyclase activities were progressively reduced as the concentration of CNA in the pretreatment was increased. However, the loss of responsiveness for the two enzymes differed in two aspects. First, the diminution of GTPase responsiveness was in agreement with the loss of binding sites and took place at concentrations of CNA that were lower than those necessary to reduce responsiveness of adenylate cyclase. Second, the loss of responsiveness of GTPase occurred simply as reduction of maximal stimulation, whereas that of adenylate cyclase involved an initial reduction of apparent agonist affinity (10-fold) that was followed by a decrease in maximal effect. We next examined the loss of responsiveness of both GTPase and adenylate cyclase in membranes prepared from cells that had been exposed to increasing concentrations of pertussis toxin (PTX) to inactivate PTX-sensitive G proteins in vivo. Also in this case, the extent of reduction in responsiveness was more pronounced for GTPase than for adenylate cyclase, especially in membranes treated with high concentrations of PTX. However, the pattern of loss was identical for the two enzymes and involved a main reduction in maximal effect of the agonist that was followed only after a large degree of inactivation (greater than 60%) by a diminished apparent affinity for the agonist. Opioid receptor-mediated inhibition of cAMP accumulation in intact cells exhibits an IC50 for the agonist that is 30-10 times lower than that measured in membranes for stimulation of GTPase or inhibition of cyclase, respectively. Treatment of cells with either CNA (1 microM) or various concentrations of PTX altered the concentration-response curves for agonist-mediated inhibition of cAMP accumulation in a manner similar to that observed for adenylate cyclase in membranes, inasmuch as both maximal inhibition and apparent affinities for the agonist were decreased. However, this decrease in affinity (5-fold) was not sufficient to eliminate the discrepancy in agonist potency between membranes and intact cells.(ABSTRACT TRUNCATED AT 400 WORDS)


Lipocalin-like prostaglandin D synthase (L-PGDS) concentration in aqueous humour in patients with open-angle glaucoma.
To report on the concentration of lipocalin-like prostaglandin D synthase (L-PGDS) in the aqueous humour (AH) in patients with open-angle glaucoma (OAG). Prospective assessment in 20 patients (13 female, 7 male, mean age 74±10.6 y) who underwent surgery for OAG. AH was sampled and analyzed for L-PGDS concentration. AH from 26 patients (11 female, 15 male, 72.4±14.4 y) without glaucoma who underwent cataract surgery, served as control subjects. The L-PGDS concentration in the AH sampled from the anterior chamber in the OAG group (5.9±2.4 mg/L) was significantly (P<0.001) higher than in the control group (3.3±1.3 mg/L). There were no significant differences between the concentrations of L-PGDS between the left and the right eye or between genders. L-PGDS concentration in the AH of patients with OAG was significantly elevated compared with its concentration in the AH of nonglaucomatous eyes. As L-PGDS is a biologically pluripotent protein, its possible role in glaucoma warrants further examination.


SEPIVAC: a community-based study of stroke incidence in Umbria, Italy.
The SEPIVAC study is a community-based epidemiological survey of incidence and outcome of acute cerebrovascular disease in the Sixth Local Health Unit, Umbria, Italy (population 49,218). The study was carried out from 1 September 1986 to 31 August 1989. There were 375 patients who were registered with a first ever stroke, with a crude rate of 2.54 (95% confidence limits 2.29-2.81) per 1000 per year; the rate adjusted to the European population is 1.55 (CL 1.36-1.77). The age adjusted relative risk for males is 1.35 (CL 1.10-1.66). Up to 15% of the patients were not admitted to hospital during the acute phase of their disease. At least 286 (76.3%, CL 72-80.6) of the cases were due to cerebral ischaemia; in 56 of these (19.6%, CL 15-24.2) a clinical diagnosis of lacunar ischaemia was made. The 30 day case fatality rate was 20.3% (CL 16.2-24.3); between one and six months 7.5% (CL 5-10.6) of patients died.


Interrogation of living myocardium in multiple static deformation states with diffusion tensor and diffusion spectrum imaging.
Diffusion tensor magnetic resonance imaging (MRI) reveals valuable insights into tissue histo-anatomy and microstructure, and has steadily gained traction in the cardiac community. Its wider use in small animal cardiac imaging in vivo has been constrained by its extreme sensitivity to motion, exaggerated by the high heart rates usually seen in rodents. Imaging of the isolated heart eliminates respiratory motion and, if conducted on arrested hearts, cardiac pulsation. This serves as an important intermediate step for basic and translational studies. However, investigating the micro-structural basis of cardiac deformation in the same heart requires observations in different deformation states. Here, we illustrate the imaging of isolated rat hearts in three mechanical states mimicking diastole (cardioplegic arrest), left-ventricular (LV) volume overload (cardioplegic arrest plus LV balloon inflation), and peak systole (lithium-induced contracture). An optimised MRI-compatible Langendorff perfusion setup with the radio-frequency (RF) coil integrated into the wet chamber was developed for use in a 9.4T horizontal bore scanner. Signal-to-noise ratio improved significantly, by 75% compared to a previous design with external RF coil, and stability tests showed no significant changes in mean T1, T2 or LV wall thickness over a 170 min period. In contracture, we observed a significant reduction in mean fractional anisotropy from 0.32 ± 0.02 to 0.28 ± 0.02, as well as a significant rightward shift in helix angles with a decrease in the proportion of left-handed fibres, as referring to the locally prevailing cell orientation in the heart, from 24.9% to 23.3%, and an increase in the proportion of right-handed fibres from 25.5% to 28.4%. LV overload, in contrast, gave rise to a decrease in the proportion of left-handed fibres from 24.9% to 21.4% and an increase in the proportion of right-handed fibres from 25.5% to 26.0%. The modified perfusion and coil setup offers better performance and control over cardiac contraction states. We subsequently performed high-resolution diffusion spectrum imaging (DSI) and 3D whole heart fibre tracking in fixed ex vivo rat hearts in slack state and contracture. As a model-free method, DSI augmented the measurements of water diffusion by also informing on multiple intra-voxel diffusion orientations and non-Gaussian diffusion. This enabled us to identify the transition from right- to left-handed fibres from the subendocardium to the subepicardium, as well as voxels in apical regions that were traversed by multiple fibres. We observed that both the mean generalised fractional anisotropy and mean kurtosis were lower in hearts in contracture compared to the slack state, by 23% and 9.3%, respectively. While its heavy acquisition burden currently limits the application of DSI in vivo, ongoing work in acceleration techniques may enable its use in live animals and patients. This would provide access to the as yet unexplored dimension of non-Gaussian diffusion that could serve as a highly sensitive marker of cardiac micro-structural integrity.


The prevalence of celiac disease in patients fulfilling Rome III criteria for irritable bowel syndrome.
Celiac disease shares several symptoms which constitute some of the ROME criteria used for the diagnosis of irritable bowel syndrome (IBS), and as such many patients with underlying Celiac disease may be mistakenly diagnosed as having IBS. The aim of the present study was to determine the prevalence of Celiac disease in patients with IBS fulfilling ROME III criteria. Patients who fulfilled ROME III criteria for irritable bowel syndrome were screened for Celiac disease using the Biocard(TM) Celiac Disease Stick test, and patients who tested positive had their serum samples analyzed for antigliadin IgA and IgG, and anti-tissue transglutaminase IgA antibodies. Patients with detectable antibody levels underwent endoscopic duodenal biopsy to confirm a diagnosis of Celiac disease. Two of 100 patients who were diagnosed as having irritable bowel syndrome as per the Roma III criteria were found to have elevated levels of serum antigliadin IgA and IgG, and anti-tissue transglutaminase IgA antibodies, with histological evidence of Celiac disease on examination of duodenal biopsy. Both patients were started on a gluten-free diet, showing significant improvement in their symptoms on follow-up. Celiac disease is a common finding among patients labeled as IBS. Celiac disease must be considered in differential diagnosis of IBS especially in the therapy refractory group.


Local ampullary resection with careful intraoperative frozen section evaluation for presumed benign ampullary neoplasms.
Frozen section evaluation has been reported to be inaccurate in detecting foci of adenocarcinoma within adenomas of the ampulla of Vater, leading many authors to advocate pancreaticoduodenectomy as the method of treatment for these neoplasms. The authors hypothesized that (1) ampullary resection is less morbid than pancreaticoduodenectomy, and (2) frozen section evaluation following ampullary resection is accurate and allows for a selective application of pancreaticoduodenectomy to those with carcinoma or benign lesions too large to be locally resected. A retrospective review of a single-surgeon experience was conducted. Thirty-eight patients who underwent ampullary resection and pancreaticoduodenectomy (39 procedures) for benign and malignant ampullary neoplasms were identified. Our technique of step-frozen section analysis is described. Twenty-one ampullary resections were performed for preoperative diagnoses of benign (16) and malignant (5) ampullary neoplasms. Frozen section evaluation accurately predicted the final histology in all patients undergoing ampullary resection. Ampullary resection (vs pancreaticoduodenectomy) was associated with a statistically lower operative time (169 minutes vs 268 minutes), estimated blood loss (192 mL vs 727 mL), mean length of stay (10 days vs 25 days), and overall morbidity (29% vs 78%). Frozen section evaluation of ampullary neoplasms is accurate. Because ampullary resection is less morbid than pancreaticoduodenectomy and frozen section evaluation is accurate, ampullary resection with frozen section evaluation is our current approach to the treatment of small benign ampullary neoplasms.


A molecular footprint of limb loss: sequence variation of the autopodial identity gene Hoxa-13.
The homeobox gene Hoxa-13 codes for a transcription factor involved in multiple functions, including body axis and hand/foot development in tetrapods. In this study we investigate whether the loss of one function (e.g., limb loss in snakes) left a molecular footprint in exon 1 of Hoxa-13 that could be associated with the release of functional constraints caused by limb loss. Fragments of the Hoxa-13 exon 1 were sequenced from 13 species and analyzed, with additional published sequences of the same region, using relative rates and likelihood-ratio tests. Five amino acid sites in exon 1 of Hoxa-13 were detected as evolving under positive selection in the stem lineage of snakes. To further investigate whether there is an association between limb loss and sequence variation in Hoxa-13, we used the random forest method on an alignment that included shark, basal fish lineages, and "eu-tetrapods" such as mammals, turtle, alligator, and birds. The random forest method approaches the problem as one of classification, where we seek to predict the presence or absence of autopodium based on amino acid variation in Hoxa-13 sequences. Different alignments tested were associated with similar error rates (18.42%). The random forest method suggested that phenotypic states (autopodium present and absent) can often be correctly predicted based on Hoxa-13 sequences. Basal, nontetrapod gnat-hostomes that never had an autopodium were consistently classified as limbless together with the snakes, while eu-tetrapods without any history of limb loss in their phylogeny were also consistently classified as having a limb. Misclassifications affected mostly lizards, which, as a group, have a history of limb loss and limb re-evolution, and the urodele and caecilian in our sample. We conclude that a molecular footprint can be detected in Hoxa-13 that is associated with the lack of an autopodium; groups with classification ambiguity (lizards) are characterized by a history of repeated limb loss and possible limb re-evolution.


Distinct pathways to refill ACh-sensitive internal Ca2+ stores in canine airway smooth muscle.
The ability of extracellular Ca2+ to refill internal Ca2+ stores of canine tracheal smooth muscle after a prior depletion by acetylcholine (ACh) was assessed using a novel sarcoplasmic reticulum (SR) Ca2+ pump inhibitor, cyclopiazonic acid (CPA). The transient contraction induced by ACh in a medium free of Ca2+ was used as an index for the content of agonist-sensitive intracellular Ca2+ stores. CPA inhibited in a concentration-dependent manner the refilling of the stores occurring during high KCl stimulation, and this inhibitory effect was independent of the external Ca2+ concentration. On the other hand, CPA was less effective in inhibiting the refilling occurring during prolonged ACh stimulation, especially when external Ca2+ concentration was raised. At 5.0 mM external Ca2+ or when 0.1 microM BAY 8644 was present in the medium, CPA was ineffective in inhibiting the refilling occurring during prolonged ACh stimulation. The maximum ACh-induced contraction in Ca(2+)-containing medium was independent of the extent of internal store Ca2+ load in the absence of L-type Ca2+ channel blocker but was highly dependent on the extent of internal Ca2+ load in the presence of the Ca2+ channel blocker. Hyperpolarization of the plasma membrane with the K+ channel opener cromakalim reduced the amplitude of ACh tonic contraction. Subsequent addition of nifedipine further reduced ACh tonic contraction. It is concluded that two different pathways for external Ca2+ are used to refill ACh-sensitive internal stores. One involves active Ca2+ uptake via a CPA-sensitive Ca2+ pump, and the other involves a CPA-insensitive pathway whose nature remains to be determined.


A Look Under the Hood: Regulatory Policy Making and the Affordable Care Act.
The Affordable Care Act (ACA) was signed into law a decade ago. Partisanship has limited the number of statutory changes, leaving the law mostly unchanged across the past 10 years. However, the ACA delegated vast powers to the executive branch, which opened the door for significant regulatory policy-making activities (also called "rulemaking"). We collected data on all regulatory actions related to the Affordable Care Act that have been taken since its passage to provide the first exploratory analyses of both the public law itself and the ensuing rulemaking activities. We also provide illustrative examples of two controversial issues: short-term limited-duration insurance plans and contraceptive coverage for women. Despite relative statutory stasis, regulatory actions have continued to shape the implementation of the Affordable Care Act. Both the Obama and Trump administrations have taken advantage of a vast delegation of policy-making power. Importantly, regulatory policy making holds the potential to yield significant changes depending on the policy goals of the presidential administration. Scholars, policy makers, and the public are well-advised to pay attention to ACA-related rulemaking activities. Moreover, "quasi-rulemaking" (i.e., the use of agency guidance as a policy tool) remains largely unexplored but could indicate an even greater regulatory enterprise than illustrated here.


Predictors of frequent visits to a psychiatric emergency room: a large-scale register study combined with a small-scale interview study.
The role of the psychiatric emergency services has undergone extensive changes following a significant downsizing of the number of psychiatric hospital beds during the past decades. A relatively small number of "frequent visitors" accounts for a disproportionately large amount of visits to psychiatric emergency services. To identify predictors of frequent use of a psychiatric emergency room at a Danish University Psychiatric Hospital through a 12-year period (1995-2007) and to speculate on how changes in the mental healthcare services affect predictors of frequent use through time. A large-scale register based logistic regression analysis combined with a small-scale explorative, interpretative interview study. Register data were drawn from the Danish Central Psychiatric Research Register. Four-year cohorts (1995, 1998, 2001 and 2004) of patients with at least one visit to the psychiatric emergency room were followed for 3 years to identify general trends of predictors throughout the period. A purposeful sample of 15 frequent visitors were interviewed about their personal motives for visiting the psychiatric emergency room, their pathways to care, and their social network and social support. The study identified two overall trends of predictors of frequent use of the psychiatric emergency room. High use of psychiatric services: ≥5 visits to the psychiatric emergency room, ≥3 admissions or ≥60 bed days during the year, was and continued to be predictive of high use of the psychiatric emergency room throughout the whole period. Furthermore, the emergence and continual presence of the predictors: severe mental illness (1999-onwards), substance abuse (2002-onwards) and sheltered housing (2002-2003-2005-onwards) indicated changes in the general profile of frequent visitors to the psychiatric emergency room, where predictors related to illness behaviour were supplemented by predictors related to disease. The changing profile of the conditions predicting frequent visits at the psychiatric emergency room was most probably related to the adverse effects of the continuous deinstitutionalising of the Danish mental health services and a radical health care reform. A basic multiplicative model was designed for the early detection of individual frequent visitors.


A new endangered species of Megaleporinus (Characiformes: Anostomidae) from the Rio de Contas basin, eastern Brazil.
A new species of Megaleporinus is described from the Rio de Contas, a coastal drainage of eastern Brazil, and its phylogenetic relationships are studied using molecular data. The new species is unique among Anostomidae by possessing two exclusive features: an irregular dark longitudinal stripe from supracleithrum to second midlateral blotch and anterior cranial fontanel partially closed. In addition, the new species is diagnosed by having three premaxillary teeth, three dentary teeth, 37 or 38 scales in lateral line, 16 scale rows around caudal peduncle, three dark midlateral blotches on body, and red fins in life. The new species is closely related to M. obtusidens from the São Francisco basin, corroborating previous studies that indicated that the latter represents a species complex as currently defined. The new species exhibits the first rib enlarged in mature males, a feature described for some congeners. The new species is herein considered to be Endangered under the IUCN criteria.


Diagnosis of cirrhosis by transient elastography (FibroScan): a prospective study.
Transient elastography (FibroScan) is a new, non-invasive, rapid, and reproducible method allowing evaluation of liver fibrosis by measurement of liver stiffness. In cirrhotic patients, liver stiffness measurements range from 12.5 to 75.5 kPa. However, the clinical relevance of these values is unknown. The aim of this prospective study was to evaluate the accuracy of liver stiffness measurement for the detection of cirrhosis in patients with chronic liver disease. A total of 711 patients with chronic liver disease were studied. Aetiologies of chronic liver diseases were hepatitis C virus or hepatitis B virus infection, alcohol, non-alcoholic steatohepatitis, other, or a combination of the above aetiologies. Liver fibrosis was evaluated according to the METAVIR score. Stiffness was significantly correlated with fibrosis stage (r=0.73, p<0.0001). Areas under the receiver operating characteristic curve (95% confidence interval) were 0.80 (0.75-0.84) for patients with significant fibrosis (F>2), 0.90 (0.86-0.93) for patients with severe fibrosis (F3), and 0.96 (0.94-0.98) for patients with cirrhosis. Using a cut off value of 17.6 kPa, patients with cirrhosis were detected with a positive predictive value and a negative predictive value (NPV) of 90%. Liver stiffness was significantly correlated with clinical, biological, and morphological parameters of liver disease. With an NPV>90%, the cut off values for the presence of oesophageal varices stage 2/3, cirrhosis Child-Pugh B or C, past history of ascites, hepatocellular carcinoma, and oesophageal bleeding were 27.5, 37.5, 49.1, 53.7, and 62.7 kPa, respectively. Transient elastography is a promising non-invasive method for detection of cirrhosis in patients with chronic liver disease. Its use for the follow up and management of these patients could be of great interest and should be evaluated further.


The fake fat phenomenon in organizing pleuritis: a source of confusion with desmoplastic malignant mesotheliomas.
We report 9 patients with pleural biopsies referred because of concern about infiltration of what appeared to be chest wall fat by pan-keratin-positive spindled cells, a finding that led to a consideration of desmoplastic mesothelioma. All patients showed pleural effusions/pleural thickening on computed tomographic scan. Pleural biopsy showed a greatly thickened and fibrotic paucicellular pleura with circular fat-like spaces and, sometimes, adjacent oblate spaces mostly deep in the fibrotic area. Indistinct, keratin-positive, spindle cells arranged parallel to the pleural surface coursed between these fat-like spaces. S-100 stains were negative around the fat-like spaces. Vimentin stains showed that the spaces did not have a cellular lining of any kind. Sometimes the spaces contained faintly hematoxyphilic material that was Alcian blue positive, and similar material was seen in the fibrotic stroma. Follow-up with periods ranging from 6 to 30 months revealed that 8 cases had stable disease on chest imaging or by clinical findings. One case had slowly progressive pleural thickening. These observations suggest that spaces resembling fat may be encountered in fibrotic pleurae and that horizontally oriented keratin-positive spindled cells between the fat-like spaces deep in the fibrotic portion of a thickened pleura represent a benign finding seen in some cases of organizing pleuritis/fibrothorax. The spaces themselves are probably artifacts derived from the biopsy procedure and/or cutting artifacts. In contrast, in true desmoplastic mesotheliomas there is downward, rather than horizontal, growth of keratin-positive spindled cells running between clearly definable fat cells.


Response of Extreme Rainfall for Landfalling Tropical Cyclones Undergoing Extratropical Transition to Projected Climate Change: Hurricane Irene (2011).
Extreme rainfall and flooding associated with landfalling tropical cyclones (TCs) have large societal impacts, both in fatalities and economic losses. This study examines the response of TC rainfall to climate change projected under future anthropogenic greenhouse emissions, focusing on Hurricane Irene, which produced severe flooding across the Northeastern United States in August 2011. Numerical simulations are made with the Weather Research and Forecasting model, placing Irene in the present-day climate and one projected for the end of 21st century climate represented by Phase 5 of the Coupled Model Intercomparison Project Representative Concentration Pathway 8.5 scenario. Projected future changes to surface and atmospheric temperature lead to a storm rainfall increase of 32% relative to the control run, exceeding the rate expected by the Clausius-Clapeyron relation given a ~3-K lower atmospheric warming. Analyses of the atmospheric water balance highlight contributions to the increase in rainfall rate from both increased circulation strength and atmospheric moisture. Storm rainfall rate shows contrasting response to global warming during TC and extratropical transition periods. During the TC phase, Irene shows a significant increase of storm rainfall rate in inner core regions. This increase shifts to outer rainbands as Irene undergoes extratropical transition, collocated with the maximum tangential wind increase and the change of secondary circulation strength. Changes of storm track from the control run to global warming projections play a role in the change of spatial rainfall pattern. Distinct roles of surface and atmospheric warming in storm rainfall and structure changes are also examined.


Curcumin inhibits telomerase activity in human cancer cell lines.
Curcumin, one of the major components of tumeric, the dried rhizome of Curcuma longa L, has been shown to have anti-proliferating and anti-carcinogenic properties. In this study, we examined the effects of curcumin on cell growth and telomerase activity in human cancer cell lines Bel7402, HL60 and SGC7901. Curcumin (1-32 microM) showed anti-proliferating effects on these cell lines in a dose-dependent manner in vitro, and anti-tumor effects when curcumin (50-200 mg/kg) was orally administered to nude mice transplanted with the cancer cells. When the cells were treated with 1 microM of curcumin for 120 h, apoptotic cells were observed by means of the adridine orange/ethidium bromide staining method, single cell microgel electrophoresis and flow cytometric analysis. On the other hand, suppression of telomerase activity in extracts of the cells treated with 1 microM of curcumin was observed by means of a telomeric repeat amplification protocol - silver staining assay. These results suggest that curcumin could suppress telomerase activity in the cancer cell lines and that the decrease of telomerase expression followed by induction of apoptosis might be involved in the anti-proliferating effect of curcumin.


Endophthalmitis after secondary intraocular lens implantation. A case-report study.
To investigate whether endophthalmitis is more common after secondary intraocular lens (IOL) implantation than after other intraocular surgeries. Risk factors, causative organisms, and visual acuity outcomes of endophthalmitis after secondary IOL implantation were investigated. The ten cases consisted of all patients treated at the Bascom Palmer Eye Institute between January 1, 1984, and December 31, 1994, for endophthalmitis after secondary IOL implantation. The 34 control patients consisted of all patients who underwent secondary IOL implantation within 3 years of the case patients (6-year span) by the same surgeons but who did not develop endophthalmitis. Demographic and clinical data were abstracted from patients' medical records. Fifty percent (5 of 10) of case patients had a history of diabetes mellitus, compared with 5.9% (2 of 34) of control patients. All three posterior chamber IOLs among case patients had transscleral suture fixation, whereas all four posterior chamber IOLs among control patients were in the sulcus without scleral sutures. Case patients were more likely than control patients to have IOLs with polypropylene haptics (30.0% and 5.9%, respectively) and to have had their IOLs placed through a superior rather than a temporal incision (70.0% and 17.9%, respectively). Eighty percent of case patients and 14.7% of control patients had either eyelid abnormalities (marked blepharitis, ectropion) or postoperative wound defects. Staphylococcus epidermidis was isolated in 50% of case patients. After treatment, 90.0% of case patients achieved a visual acuity of greater than or equal to 20/100. Endophthalmitis after secondary IOL implantation was associated with diabetes, transscleral suture fixation of posterior chamber IOLs, polypropylene haptics, preoperative eyelid abnormalities, re-entry of eye through a previous wound, and postoperative wound defects. Most cases were caused by Staphylococcus epidermidis, and the post-treatment visual outcomes were generally good.


Healthy Beat Acupunch exercise program: Validation and feasibility study for older adults with reduced physical capacity or probable sarcopenia.
This research aims to validate the Healthy Beat Acupunch (HBA) exercise program, determine the feasibility of the HBA exercise program protocol and gain an understanding of the effects on well-being for older adults with sarcopenia. Design, Setting & Intervention: Validation of the HBA exercise program was conducted using two rounds of Delphi communication among eight experts. A one-group, pre-post experimental study was conducted with 17 older adults with probable sarcopenia and/or low gait speed at an Australian retirement village. The HBA exercise program lasted 40 min per session, three sessions per week for four weeks. Muscle mass, muscle strength, gait speed and health-related quality of life were assessed before and after the intervention. The HBA exercise program was evaluated via a questionnaire and individual interviews. Experts validated the HBA exercise program and deemed it to be simple, safe, suitable and helpful for practice by older adults with sarcopenia. Participants enjoyed the HBA exercise program, planned to continue and would recommend to friends. Frequency, duration and size of the exercise class were appropriate, and they appreciated the trainer's support and directions when mastering the exercise motions. Improvement in participants' gait speed was found post-exercise intervention (p<.005). The HBA exercise program is appropriate for practice by older adults, particularly those with reduced physical capacity and probable sarcopenia with possible benefits of improved gait speed. Future studies need to consider and overcome the limitations (i.e. study design, sample size) and challenge (participant recruitment) encountered in this research.


Graph analysis of functional brain networks for cognitive control of action in traumatic brain injury.
Patients with traumatic brain injury show clear impairments in behavioural flexibility and inhibition that often persist beyond the time of injury, affecting independent living and psychosocial functioning. Functional magnetic resonance imaging studies have shown that patients with traumatic brain injury typically show increased and more broadly dispersed frontal and parietal activity during performance of cognitive control tasks. We constructed binary and weighted functional networks and calculated their topological properties using a graph theoretical approach. Twenty-three adults with traumatic brain injury and 26 age-matched controls were instructed to switch between coordination modes while making spatially and temporally coupled circular motions with joysticks during event-related functional magnetic resonance imaging. Results demonstrated that switching performance was significantly lower in patients with traumatic brain injury compared with control subjects. Furthermore, although brain networks of both groups exhibited economical small-world topology, altered functional connectivity was demonstrated in patients with traumatic brain injury. In particular, compared with controls, patients with traumatic brain injury showed increased connectivity degree and strength, and higher values of local efficiency, suggesting adaptive mechanisms in this group. Finally, the degree of increased connectivity was significantly correlated with poorer switching task performance and more severe brain injury. We conclude that analysing the functional brain network connectivity provides new insights into understanding cognitive control changes following brain injury.


Uptake, prevalence and predictors of first-time use for the 75+ Health Assessment Scheme.
In 1999, the Australian Federal Government introduced Medicare items for Health Assessments for people aged 75 years and older (75+ health assessments). This research examined uptake of these assessments and identified predictors of use by women from the Australian Longitudinal Study on Women's Health (ALSWH). Assessments were identified for each year from 1999 to 2013 using linked Medicare data. Time to first assessment was examined, as well as social and health factors associated with having an assessment. From 1999 to 2013, 61.8% of women had at least one assessment. Almost one-third had an assessment within 2 years of their introduction, 25% of women died before having an assessment and 13% survived but did not have an assessment. Factors associated with assessment included being widowed, private health insurance, marital status, education, having arthritis and urinary incontinence, and less difficulty managing on income. Many women never received an assessment, and many only received one. Promotion of the 75+ health assessments is necessary among older women to increase uptake.


Effects of Panax notoginseng saponins on vascular endothelial cells in vitro.
To investigate the inhibition of endothelium-dependent in vitro vascular relaxation induced by the total saponins (gensenosides) from Panax notoginseng (PNS) and the effect of PNS on the cytosolic Ca2+ concentration on cultured bovine pulmonary artery endothelial cells. The endothelial-dependent vascular relaxation was assessed using acetylcholine (ACh) or cyclopiazonic acid (CPA) induced relaxation in endothelium-intact rat aorta. Cytosolic Ca2+ level was assessed in real time using dynamic digital fluorescence ratio imaging. In addition to its direct relaxation of the smooth muscle cells at high concentrations, PNS, at 100 mg/L having little effect on smooth muscle, caused a marked inhibition of endothelium-dependent relaxation brought about by PNS. This inhibitory effect was due to its inhibition of elevation of cytosolic Ca2+, which is required for the activation of NO generation and release from the vascular endothelial cells. Nifedipine has no effect on either the endothelium-dependent relaxation or the cytosolic Ca2+ level in the cultured endothelial cells. Our findings are consistent with the known action of PNS on receptor-operated Ca2+ channels and support our contention that PNS inhibits endothelium-dependent relaxation by preventing the increase of Ca2+ level in endothelial cells via the receptor-operated Ca2+ channels in the presence of ACh or the non-selective cation channels opened by CPA.


Radial nerve palsies associated with paediatric supracondylar humeral fractures: a caution in the interpretation of neurophysiological studies.
Traumatic and iatrogenic neurological complications associated with paediatric supracondylar humeral fractures are well recognised. The severity of the nerve injury associated with supracondylar humeral fractures can be difficult to assess clinically and relies upon clinical progression or absence of recovery and neurophysiology. It is accepted that complete nerve palsy with neurophysiological complete block and absence of clinical recovery after three months requires surgical exploration and reconstruction. However, we argue that even a partial nerve palsy that is failing to recover as expected by 3 months should be explored even when the neurophysiology suggests the nerve is in continuity. We report two cases of closed Gartland type III paediatric extension-type supracondylar humeral fractures treated with closed reduction and percutaneous pinning and open reduction and internal fixation, respectively. Both children developed persistent postoperative radial nerve motor palsy. Neurophysiological studies sought prior to exploration indicated a degree of sensory nerve function in both cases, indicating a nerve in continuity. Subsequent surgical exploration revealed interfragmentary radial nerve compression at the fracture site at two levels in one case and at one level in the second case. The site of compression was excised and the nerve grafted. Excellent near-normal radial nerve recovery was achieved except for the persistent loss of extensor carpi radialis function in the first child. We publish these findings to highlight the possibility of misinterpreting the incomplete nerve lesion and the neurophysiology of a nerve in continuity, as a nerve that would spontaneously recover. At exploration, in these two cases, it was clear by the level of interfragmentary compression that the nerve would not have recovered without surgical intervention. We recommend exploration and repair of the radial nerve, when function to the nerve is compromised, even in the face of neurophysiological evidence of an intact nerve.


"When you carry condoms all the boys think you want it": negotiating competing discourses about safe sex.
With the advent of HIV, sexual health campaigns and formal sex education in schools have worked to instil the concept of safe sex into the collective minds of Australia's youth. However the concept in its present guise is a fairly limited one. We argue in this paper that the predominant emphasis in education programmes on safe sex as condom use may be counter-productive for some young heterosexuals for two reasons. First, this strategy is male-focused and may not extrapolate well to young women who face special risks around pregnancy and rigid societal gender norms which govern sexual behaviour. Second, health promotion strategies aimed at young heterosexuals are based on an assumption of rational decision-making in sexual encounters and obscure the non-rational nature of arousal and desire, and the unequal power relations that exist between young men and women engaging in sex. Five hundred and twelve senior rural students participated in the study which included group discussions about sexuality and survey items which focused on the meanings of safe sex and the accessibility and use of condoms. The results showed that though most students identified condoms with safe sex, many were ambivalent about using them. Reasons given related to problems of negotiation, difficulties of access, and the risks which condoms gave no protection from, such as a sullied reputation. Perhaps, partly because of this, some students were looking to less secure methods of protection such as informal history-taking and monogamy. It is argued that successful sexual health promotion strategies must address the broad spectrum of concerns facing young men and women when they become sexually active and that consideration be given to the social context in which young people conduct their sexual lives.


Programmable Multivalent DNA-Origami Tension Probes for Reporting Cellular Traction Forces.
Mechanical forces are central to most, if not all, biological processes, including cell development, immune recognition, and metastasis. Because the cellular machinery mediating mechano-sensing and force generation is dependent on the nanoscale organization and geometry of protein assemblies, a current need in the field is the development of force-sensing probes that can be customized at the nanometer-length scale. In this work, we describe a DNA origami tension sensor that maps the piconewton (pN) forces generated by living cells. As a proof-of-concept, we engineered a novel library of six-helix-bundle DNA-origami tension probes (DOTPs) with a tailorable number of tension-reporting hairpins (each with their own tunable tension response threshold) and a tunable number of cell-receptor ligands. We used single-molecule force spectroscopy to determine the probes' tension response thresholds and used computational modeling to show that hairpin unfolding is semi-cooperative and orientation-dependent. Finally, we use our DOTP library to map the forces applied by human blood platelets during initial adhesion and activation. We find that the total tension signal exhibited by platelets on DOTP-functionalized surfaces increases with the number of ligands per DOTP, likely due to increased total ligand density, and decreases exponentially with the DOTP's force-response threshold. This work opens the door to applications for understanding and regulating biophysical processes involving cooperativity and multivalency.


First Report of Leaf Spot caused by Bipolaris oryzae on Switchgrass in Tennessee.
Knowledge of pathogens in switchgrass, a potential biofuels crop, is limited. In December 2007, dark brown to black irregularly shaped foliar spots were observed on 'Alamo' switchgrass (Panicum virgatum L.) on the campus of the University of Tennessee. Symptomatic leaf samples were surface-sterilized (95% ethanol, 1 min; 20% commercial bleach, 3 min; 95% ethanol, 1 min), rinsed in sterile water, air-dried, and plated on 2% water agar amended with 3.45 mg fenpropathrin/liter (Danitol 2.4 EC, Valent Chemical, Walnut Creek, CA) and 10 mg/liter rifampicin (Sigma-Aldrich, St. Louis, MO). A sparsely sporulating, dematiaceous mitosporic fungus was observed. Fungal plugs were transferred to surface-sterilized detached 'Alamo' leaves on sterile filter paper in a moist chamber to increase spore production. Conidia were ovate, oblong, mostly straight to slightly curved, and light to olive-brown with 3 to 10 septa. Conidial dimensions were 12.5 to 17 × 27.5 to 95 (average 14.5 × 72) μm. Conidiophores were light brown, single, multiseptate, and geniculate. Conidial production was polytretic. Morphological characteristics and disease symptoms were similar to those described for Bipolaris oryzae (Breda de Haan) Shoemaker (2). Disease assays were done with 6-week-old 'Alamo' switchgrass grown from seed scarified with 60% sulfuric acid and surface-sterilized in 50% bleach. Nine 9 × 9-cm square pots with approximately 20 plants per pot were inoculated with a mycelial slurry (due to low spore production) prepared from cultures grown on potato dextrose agar for 7 days. Cultures were flooded with sterile water and rubbed gently to loosen mycelium. Two additional pots were inoculated with sterile water and subjected to the same conditions to serve as controls. Plants were exposed to high humidity by enclosure in a plastic bag for 72 h. Bags were removed, and plants were incubated at 25/20°C with 50 to 60% relative humidity. During the disease assay, plants were kept in a growth chamber with a 12-h photoperiod of fluorescent and incandescent lighting. Foliar leaf spot symptoms appeared 5 to 14 days post-inoculation for eight of nine replicates. Control plants had no symptoms. Symptomatic leaf tissue was processed and plated as described above. The original fungal isolate and the pathogen recovered in the disease assay were identified using internal transcribed spacer (ITS) region sequences. The ITS region of rDNA was amplified with PCR and primer pairs ITS4 and ITS5 (4). PCR amplicons of 553 bp were sequenced, and sequences from the original isolate and the reisolated pathogen were identical (GenBank Accession No. JQ237248). The sequence had 100% nucleotide identity to B. oryzae from switchgrass in Mississippi (GU222690, GU222691, GU222692, and GU222693) and New York (JF693908). Leaf spot caused by B. oryzae on switchgrass has also been described in North Dakota (1) and was seedborne in Mississippi (3). To our knowledge, this is the first report of B. oryzae from switchgrass in Tennessee. References: (1) D. F. Farr and A. Y. Rossman. Fungal Databases. Systematic Mycology and Microbiology Laboratory, ARS, USDA. Retrieved from http://nt.ars-grin.gov/fungaldatabases/, 28 June 2012. (2) J. M. Krupinsky et al. Can. J. Plant Pathol. 26:371, 2004. (3) M. Tomaso-Peterson and C. J. Balbalian. Plant Dis. 94:643, 2010. (4) T. J. White et al. Pages 315-322 in: PCR Protocols: a Guide to Methods and Applications. M. A. Innis et al. (eds), Acad. Press, San Diego, 1990.


Cardiovascular health in migrants: current status and issues for prevention. A collaborative multidisciplinary task force report.
To review information on cardiovascular health and migration, to stress the attention of researchers that much needs to be done in the collection of sound data in Italy and to allow policy makers identifying this issue as an important public health concern. In Italy, the rate of immigrants in the total number of residents increased from 2.5% in 1990 to 7.4% in 2010, and currently exceeds 10% in regions such as Lombardia, Emilia Romagna and Toscana. A consensus statement was developed by approaching relevant Italian national scientific societies involved in cardiovascular prevention. Task force members were identified by the president and/or the boards of each relevant scientific society or working group, as appropriate. To obtain a widespread consensus, drafts were merged and distributed to the scientific societies for local evaluation and revision by as many experts as possible. The ensuing final draft was finally approved by scientific societies. In several western European countries, the prevalence of hypertension, diabetes, chronic kidney disease, obesity and metabolic syndrome was found to be higher among immigrants than in the native population. Although migrants are often initially healthier than non-migrant populations in their host countries, genetic factors, and changing environments with lifestyle changes, social exclusion and insufficient medical control may expose them to health challenges. Cultural reasons may also hamper both the dissemination of prevention strategies and migrant communication with healthcare providers. However, great diversity exists across and within different groups of migrants, making generalizations very difficult and many countries do not collect registry or survey data for migrant's health. In the present economic context, the European Union is placing great attention to improve data collection for migrant health and to support the implementation of specific prevention policies aimed at limiting the future burden of cardiovascular and renal disease, and the consequent load for health systems. Wider initiatives on the topic are awaited in Italy.


Geographical and host species barriers differentially affect generalist and specialist parasite community structure in a tropical sky-island archipelago.
Understanding why some parasites emerge in novel host communities while others do not has broad implications for human and wildlife health. In the case of haemosporidian blood parasites, epidemic wild bird mortalities on oceanic islands have been linked to Plasmodium spp., but not genera like Haemoproteus. Indeed, Haemoproteus is absent from many oceanic islands. By contrast, birds on continental islands share long coevolutionary histories with both Plasmodium and Haemoproteus, and are thus ideal model systems to elucidate eco-evolutionary endpoints associated with these parasites in oceanic islands. Here, we examine eco-evolutionary dynamics of avian haemosporidian in the Shola sky-island archipelago of the Western Ghats, India. Our analyses reveal that compared to Plasmodium, Haemoproteus lineages were highly host-specific and diversified via co-speciation with their hosts. We show that community structure of host-generalist Plasmodium was primarily driven by geographical factors (e.g. biogeographic barriers), while that of host-specialist Haemoproteus was driven by host species barriers (e.g. phylogenetic distance). Consequently, a few host species can harbour a high diversity of Plasmodium lineages which, in turn, are capable of infecting multiple host species. These two mechanisms can act in concert to increase the risk of introduction, establishment, and emergence of novel Plasmodium lineages in island systems.


Low nephron number and its clinical consequences.
Epidemiologic studies now strongly support the hypothesis, proposed over two decades ago, that developmental programming of the kidney impacts an individual's risk for hypertension and renal disease in later life. Low birth weight is the strongest current clinical surrogate marker for an adverse intrauterine environment and, based on animal and human studies, is associated with a low nephron number. Other clinical correlates of low nephron number include female gender, short adult stature, small kidney size, and prematurity. Low nephron number in Caucasian and Australian Aboriginal subjects has been shown to be associated with higher blood pressures, and, conversely, hypertension is less prevalent in individuals with higher nephron numbers. In addition to nephron number, other programmed factors associated with the increased risk of hypertension include salt sensitivity, altered expression of renal sodium transporters, altered vascular reactivity, and sympathetic nervous system overactivity. Glomerular volume is universally found to vary inversely with nephron number, suggesting a degree of compensatory hypertrophy and hyperfunction in the setting of a low nephron number. This adaptation may become overwhelmed in the setting of superimposed renal insults, e.g. diabetes mellitus or rapid catch-up growth, leading to the vicious cycle of on-going hyperfiltration, proteinuria, nephron loss and progressive renal functional decline. Many millions of babies are born with low birth weight every year, and hypertension and renal disease prevalences are increasing around the globe. At present, little can be done clinically to augment nephron number; therefore adequate prenatal care and careful postnatal nutrition are crucial to optimize an individual's nephron number during development and potentially to stem the tide of the growing cardiovascular and renal disease epidemics worldwide.


The supercoiling state of DNA determines the handedness of both H3 and CENP-A nucleosomes.
Nucleosomes form the unit structure of the genome in eukaryotes, thereby constituting a fundamental tenet of chromatin biology. In canonical nucleosomes, DNA wraps around the histone octamer in a left-handed toroidal ramp. Here, in single-molecule magnetic tweezers studies of chaperone-assisted nucleosome assembly, we show that the handedness of the DNA wrapping around the nucleosome core is intrinsically ambidextrous, and depends on the pre-assembly supercoiling state of the DNA, i.e., it is not uniquely determined by the octameric histone core. Nucleosomes assembled onto negatively supercoiled DNA are found to exhibit a left-handed conformation, whereas assembly onto positively supercoiled DNA results in right-handed nucleosomes. This intrinsic flexibility to adopt both chiralities is observed both for canonical H3 nucleosomes, and for centromere-specific variant CENP-A nucleosomes. These data support recent advances suggesting an intrinsic adaptability of the nucleosome, and provide insights into how nucleosomes might rapidly re-assemble after cellular processes that generate positive supercoiling in vivo.


National and education-specific trends in life and health expectancies in Denmark 2004-2015.
Several studies have revealed widening of inequalities in life expectancy, but little is known about the recent changes in health expectancy nationally and between socioeconomic groups. This study examines dynamics of national and education-specific life expectancy and health expectancies at age 50 years in Denmark from 2004/2007 to 2015. Nationwide register data on education and mortality were linked and combined with Danish health data from the Survey of Health, Ageing and Retirement in Europe and changes in life expectancy and three health expectancy indicators were estimated by Sullivan's method. From 2004 to 2015, national life expectancy at age 50 years increased by 2.4 years for men and 2.1 years for women. Simultaneously, after an initial rapid improvement from 2004 to 2007, the pace of progress in health expectancy decreased. From 2007 to 2015, the difference in life expectancy at age 50 years between men with long and short education increased from 4.3 to 5.0 years. For women, the corresponding increase in the life expectancy gap was less pronounced from 3.5 to 3.8 years. The educational gap in lifetime without long-term illness decreased from 4.6 years to 3.1 years for men and from 6.1 years to 4.6 years for women. On the contrary, the educational gap increased for lifetime without activity limitations and in self-rated good health. Previously observed improvements in health expectancy in Denmark slowed down despite continuing progress in life expectancy. This worrying change coincides with persistent educational inequalities in life expectancy and health expectancy and is a challenge to a sustainable social and health development in the future.


Statins and stroke prevention.
Data from studies on the benefits of statins in coronary artery disease patients in preventing recurrent primary and secondary cardiac endpoints, as well as ischemic strokes, imply the potential value of statins in recurrent ischemic stroke prevention without coronary artery disease symptoms or, by extension, primary ischemic stroke prevention. However, data on the latter are lacking, although the ongoing Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) study is designed to answer that question. Until these data become available, clinicians are justified in using statins to avert recurrent ischemic strokes due to atherosclerosis, especially if elevated total cholesterol, increased low-density lipoprotein cholesterol, and/or reduced high-density lipoprotein cholesterol, as specified in the National Cholesterol Education Program Third Adult Treatment Panel, are present. This article reviews the pathophysiology of atherosclerosis, particularly the major components of atheromas of cholesterol, smooth muscle cells, inflammation, "foam cells," and connective tissue elements. Emphasis is placed on the first three and the results of statin trials in coronary artery disease, as well as the beneficial pleiotrophic effects of statins in ischemic strokes.


Determining Electric Fields in Thunderclouds With the Radiotelescope LOFAR.
An analysis is presented of electric fields in thunderclouds using a recently proposed method based on measuring radio emission from extensive air shower events during thunderstorm conditions. This method can be regarded as a tomography of thunderclouds using cosmic rays as probes. The data cover the period from December 2011 till August 2014. We have developed an improved fitting procedure to be able to analyze the data. Our measurements show evidence for the main negative-charge layer near the -10° isotherm. This we have seen for a winter as well as for a summer cloud where multiple events pass through the same cloud and also the vertical component of the electric field could be reconstructed. On the day of measurement of some cosmic-ray events showing evidence for strong fields, no lightning activity was detected within 100 km distance. For the winter events, the top heights were between 5 and 6 km, while in the summer, typical top heights of 9 km were seen. Large horizontal components in excess of 70 kV/m of the electric fields are observed in the middle and top layers.


Evaluation of biological and antimicrobial properties of freeze-dried whey fermented by different strains of Lactobacillus plantarum.
The aim of this study was to evaluate the biological and antimicrobial activities of commercial freeze-dried whey fermented by lactic acid bacteria in order to valorize this high polluting liquid waste of the dairy industry. Freeze-dried whey was fermented by different strains of Lactobacillus plantarum (CECT 220, 221, 748) at three different times of fermentation (24, 48, 72 h). Afterwards, the extract was purified on centricon amicon with a cut-off of 3 kDa to obtain a permeate consisting of small bioactive compounds reported in the literature to show greater bioactivity. The purified and diluted samples were subjected to the biological and antimicrobial tests for the evaluation of antioxidant, antihypertensive, iron binding, and antifungal activities and identification of phenolic compounds. The results highlighted a radical cation scavenging activity ranging from 1.415 to 2.083 mmol trolox equivalents TE per kg of dry weight, a percentage of iron binding capacity ranging between 23-55% and a percentage of ACE inhibitory activity ranging between 67-85%. The optimal biological activity was obtained from whey fermented by L. plantarum 220 for all the assays performed, except for the iron chelating activity. Furthermore, the antifungal analysis showed a good activity against the mycotoxigenic fungi belonging to Fusarium generum (F. moniliformis, F. graminearum and F. verticillioides), while a slight activity was obtained for Aspergillus and Penicillium generum. This antifungal activity could be correlated to the production of phenolic compounds during fermentation. The obtained results support the hypothesis of using whey as a functional ingredient to improve food preservation.


Using a chimeric respiratory chain and EPR spectroscopy to determine the origin of semiquinone species previously assigned to mitochondrial complex I.
For decades, semiquinone intermediates have been suggested to play an essential role in catalysis by one of the most enigmatic proton-pumping enzymes, respiratory complex I, and different mechanisms have been proposed on their basis. However, the difficulty in investigating complex I semiquinones, due to the many different enzymes embedded in the inner mitochondrial membrane, has resulted in an ambiguous picture and no consensus. In this paper, we re-examine the highly debated origin of semiquinone species in mitochondrial membranes using a novel approach. Our combination of a semi-artificial chimeric respiratory chain with pulse EPR spectroscopy (HYSCORE) has enabled us to conclude, unambiguously and for the first time, that the majority of the semiquinones observed in mitochondrial membranes originate from complex III. We also identify a minor contribution from complex II. We are unable to attribute any semiquinone signals unambiguously to complex I and, reconciling our observations with much of the previous literature, conclude that they are likely to have been misattributed to it. We note that, for this earlier work, the tools we have relied on here to deconvolute overlapping EPR signals were not available. Proposals for the mechanism of complex I based on the EPR signals of semiquinone species observed in mitochondrial membranes should thus be treated with caution until future work has succeeded in isolating any complex I semiquinone EPR spectroscopic signatures present.


A mutation in a Saccharomyces cerevisiae gene (RAD3) required for nucleotide excision repair and transcription increases the efficiency of mismatch correction.
RAD3 functions in DNA repair and transcription in Saccharomyces cerevisiae and particular rad3 alleles confer a mutator phenotype, possibly as a consequence of defective mismatch correction. We assessed the potential involvement of the Rad3 protein in mismatch correction by comparing heteroduplex repair in isogenic rad3-1 and wild-type strains. The rad3-1 allele increased the spontaneous mutation rate but did not prevent heteroduplex repair or bias its directionality. Instead, the efficiency of mismatch correction was enhanced in the rad3-1 strain. This surprising result prompted us to examine expression of yeast mismatch repair genes. We determined that MSH2, but not MLH1, is transcriptionally regulated during the cell-cycle like PMS1, and that rad3-1 does not increase the transcript levels for these genes in log phase cells. These observations suggest that the rad3-1 mutation gives rise to an enhanced efficiency of mismatch correction via a process that does not involve transcriptional regulation of mismatch repair. Interestingly, mismatch repair also was more efficient when error-editing by yeast DNA polymerase delta was eliminated. We discuss our results in relation to possible mechanisms that may link the rad3-1 mutation to mismatch correction efficiency.


Birch allergen challenges in allergic conjunctivitis using standard conjunctival allergen challenge and environmental exposure chamber.
Environmental exposure chambers (EECs) have been used extensively to study allergic rhinoconjunctivitis. Few studies have been published using EECs in conjunctivitis only, and none have used conjunctival allergen challenge as a selection criterion. The present study validated ALYATEC EEC in allergic conjunctivitis to birch pollen. Sixteen patients with a positive conjunctival allergen challenge (CAC) were exposed to 60 ng/m3 of Bet v 1 in an EEC on two consecutive days for a maximum of 4 h to validate EEC exposure to birch. Reproducibility was tested among seven of the patients. A conjunctival positive scoring during the CAC and the EEC exposure was defined as a Total Ocular Symptom Score (TOSS) ≥ 5. Fifty percent of patients had a conjunctival positive scoring during first exposure and 75% during second exposure. The mean time to a conjunctival response was 81.2 ± 33.9 min and 101.6 ± 57 (P > 0.05) during first and second exposure, respectively. No difference in TOSS occurred between the two exposures. The time necessary to obtain a positive response during the CAC was significantly shorter than with the EEC. The estimated quantity of Bet v 1 inducing a positive response was 0.07 ± 0.03 ng (exposure 1), 0.07 ± 0.07 ng (exposure 2), 980 ± 784 ng (CAC). Conjunctival positive scoring and quantity of Bet v 1 was reproducible in all six EEC exposures. Early conjunctival responses induced by birch allergen exposures in EEC were different than from those identified with direct instillation during CAC. EEC appears to be closer to natural exposure than CAC.


Carbonic anhydrase and osteoclasts: localization by labeled inhibitor autoradiography.
Autoradiography with tritiated acetazolamide indicates that osteoclasts of the hen and chick contain concentrations of carbonic anhydrase which are similar to those in pancreatic acinar cells. Grain counts of osteoblasts and osteocytes were not different from background. Thus, a sufficient quantity of carbonic anhydrase seems to be present in osteoclasts to be of physiological importance in bone resorption.