Chlorogenic acid improves the intestinal barrier by relieving endoplasmic reticulum stress and inhibiting ROCK/MLCK signaling pathways.
Phenolic acids play an active role in protecting the intestinal barrier, the structural integrity and function of which are crucial for host health. In the present study, we aimed to identify phenolic compounds that protect the intestine and explore the underlying mechanisms. We performed an imaging-based, quantitative, high-content screening (using Caco-2 and LS174T incubated with lipopolysaccharide/palmitic acid, respectively) to identify phenolic acids that could improve the mucosal barrier. We found that chlorogenic acid (CGA), 5-caffeoylquinic acid, protocatechuic acid, and caffeic acid alleviated intestinal barrier disruption. Furthermore, CGA increased transepithelial electrical resistance (TEER) and decreased paracellular permeability. Mechanistically, CGA inhibited the activation of myosin light chain kinase (MLCK) and Rho-associated kinase 1 (ROCK1) signals, thereby downregulating the expression of the downstream molecules phosphorylated myosin phosphatase target subunit 1 (p-MYPT1), MLCK, and phosphorylated myosin light chain (p-MLC), and upregulating the expression of tight junction proteins. In addition, CGA alleviated endoplasmic reticulum (ER) stress by inhibiting the expression levels of ER markers [glucose-regulated protein78 (GRP78) and C/EBP homologous protein (CHOP)] and the nuclear translocation of activating transcription factor 6 (ATF6), thereby promoting the expression of mucin [mucin 2 (Muc2), mucin 5AC (MUC5AC)] and secretory factor trefoil factor family 3 (TFF3) proteins. In summary, we identified four substances that can stabilise intestinal homeostasis. Of these, CGA protects the intestinal barrier by inhibiting ROCK/MLCK signalling pathways and relieving ER stress. These findings highlight the importance of rapidly screening potential active ingredients that benefit the intestinal barrier and provide a theoretical basis for enteral nutrition.


[Study on pan-resistant Klebsiella pneumoniae harboring blaKPC-2 type carbapenemase gene from a hospital outbreak in Huzhou, Zhejiang].
To investigate the status of genotype of the KPC (Klebsiella pneumoniae carbapenemase)-encoding genes in Pan-resistant K. Pneumoniae, isolated from the 98th Hospital of People's Liberation Army, Huzhou district, Zhejiang province, China. 19 strains of Pan-resistant K. pneumoniae were isolated from the inpatients between November, 2008 and July, 2009. Phenotypic confirmatory test for suspected carbapenemases production were carried out by Modified Hodge test. Carbapenemase gene of bla(KPC) was analyzed by PCR and verified by DNA sequencing. In 19 strains of K. pneumoniae, the positive rates of Modified Hodge test and gene of bla(KPC) were both 100.0%. These genes all belonged to bla(KPC-2) subtype confirmed by nucleotide sequence analysis. Among them, the bla(KPC-2) gene sequence of the HZ001 strain (its original serial number was HZ9871) had been registered in GenBank (GenBank Accession Number: GU086225). All of the Pan-resistant K. pneumoniae isolated from the inpatients harbored bla(KPC-2) type carbapenemases gene and causing an outbreak in a hospital. Carbapenemases that producing type KPC-2 might be the major reason which causing the resistance to Carbapenems antibiotics.


Nonequilibrium thermodynamics of interfaces using classical density functional theory.
A vapor-liquid interface introduces resistivities for mass and heat transfer. These resistivities have recently been determined from molecular simulations, as well as theoretically using the van der Waals square gradient model. This model, however, does not allow for direct quantitative comparison to experiment or results from molecular simulations. The classical density functional theory is used here in order to determine the equilibrium profiles of vapor-liquid interfaces. Equilibrium profiles are sufficient in the framework of nonequilibrium thermodynamics for determining the interfacial resistivities. The interfacial resistivities for heat transfer, for mass transfer, and for the coupling of heat and mass transfer can all be related to only one local thermal resistivity. This is done with integral relations for the interfacial resistivities. All interfacial resistivities can be consistently described in their temperature behavior with good accuracy.


Elderly bedridden patients with dementia use over one quarter of resources in internal medicine wards in an Israeli hospital.
Elderly bedridden patients with dementia (EBRPD) are a growing segment of the population. We aimed to describe acute care hospitalization of EBRPD in internal medicine wards: the prevalence of EBRPD, their impact on hospital resources and hospital ecology, one-year survival, and one-year readmission-free survival. The study setting was the internal medicine division of one tertiary care hospital in Israel. We conducted a point-prevalence survey to measure the prevalence of EBRPD and the prevalence of multidrug-resistant organism (MDRO) carriage. We also conducted a retrospective chart review of EBRPD who were hospitalized in the internal medicine division in order to assess resource use, survival, and readmission. In the point prevalence surveys (N = 1667 patients), EBRPD comprised 24.3% of patients and 59.0% of mechanically ventilated patients. EBRPD were twice as likely to be colonized or infected by MDROs as other patients (39.3% vs. 18%, p < 0.001); thus, 41% of MDRO carriers during the survey days were EBRPD. In the retrospective study (N = 517 EBRPD), 80% of EBRPD received antibiotics; on average, they received an antibiotic on 87.7% of their hospital days. One-year survival was 35.6% and one-year readmission-free survival was 16.4%. Acute care hospitalization of EBRPD accounted for a high proportion of bed occupancy and ventilator use in internal medicine wards. EBRPD significantly increase the potential for MDRO transmission. Policymakers should seek alternatives to acute care hospitalization for EBRPD.


Synthesis of part of a mouse immunoglobulin light chain in a bacterial clone.
We have cloned double stranded cDNA sequences encoding a mouse immunoglobulin light chain (L-321) into the PstI site of the beta-lactamase gene of plasmid pBR322 by the oligo (dG)-oligo (dC) tailing procedure. Escherichia coli X1776 transformed by the recombinant plasmids were screened for the expression of L-321 antigenic determinants by a newly developed in situ radio-immunoassay. One out of seven transformants screened was found to synthesize an L-chain like protein. Each bacterial cell produces about 550 molecules of the L-chain sequence. Preferential segregation of the L-chain sequence to the periplasmic space suggest covalent attachment of the L-chain sequence to the N-terminal portion of beta-lactamase. Restriction mapping of the plasmid DNA isolated from the positive clone indicated the presence of a DNA sequence coding for the entire constant region and extending into the variable region for a length corresponding to about 40 amino acid residues. The orientation of the cloned cDNA with respect to the plasmid DNA is compatible with the formation of a fused beta-lactamase-L-321 peptide.


Optimizing education on the inpatient dermatology consultative service.
A consultative dermatology service plays an important role in patient care and education in the hospital setting. Optimizing education in balance with high-quality dermatology consultative services is both a challenge and an opportunity for dermatology consultation teams. There is an emergence of new information about how dermatology can best be taught in the hospital, much of which relies on principles of workplace learning as well as the science of how learning and teaching best happen in work settings. These best practices are summarized in this narrative review with integrated discussion of concepts from outpatient dermatology education and lessons learned from other inpatient teaching models. In addition, consultative dermatology curricula should utilize a blended curriculum model comprised of patient care and active learning and self-study modalities. Specific educational methods will discuss 2 strategies: (1) direct patient-care activities (ie, bedside teaching rounds) and (2) nonpatient care activities (ie, case presentations, didactic sessions, online modules, and reading lists).


Efficacy of gold nanoparticles against isoproterenol induced acute myocardial infarction in adult male albino rats.
This study was undertaken to investigate the role of gold nanoparticles (GNPs) of 50 nm diameter on isoproterenol (ISO) induced acute myocardial infarction in adult male albino rats. Forty five adult Wistar male albino rats were equally divided into three groups. Control (group I) was further subdivided into three subgroups. In group II, the rats received ISO subcutaneously at a dose of 100 mg/kg for three days. In group III, rats received ISO as group II and then GNPs (400 μg/kg/day) intravenously for 14 consecutive days. Echocardiography was performed. Left ventricular specimens were prepared for H&E, van Gieson staining, immunohistochemical analysis for (eNOs and Bcl-2), and Electron microscope examination. Energy dispersive X-ray microanalysis was also performed. Cardiac markers such as creatine Kinase-MB (CK-MB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and cardiac troponin T (cTnT) were measured. Group II revealed cardiomyocytes with deeply stained acidophilic cytoplasm, small dark nuclei, intracellular vacuolations, wide intercellular spaces, and extravasated red blood cells. Increased collagen fibers were observed. Electron microscope examination showed cardiomyocyte with small and irregular outlined nuclei, mitochondria with irregular cristae and others with ruptured mitochondrial membrane, abnormal alignment of myofibrils, dilated cisternae of smooth endoplasmic reticulum, and disorganized intercalated discs. Group III showed that most cardiomyocytes preserved the normal architecture. Increased expression of eNOs immunoreaction and decreased Bcl-2 immunoreaction were detected in group II as compared to the control and GNP-treated groups. These findings suggested that GNPs of 50 nm diameter improved myocardial injury after ISO-induced myocardial infarction in rats. Myocardial infarction (MI), Isoproterenol (ISO), Nitric oxide (NO), Neuronal NOS (nNOs), Endothelial NOs (eNOs), Gold nanoparticle (GNPs), Diamiobenzidine (DAB), Serum Creatine Kinase-MB (CK-MB), Alanine aminotransferase (ALT), Cardiac troponin T (cTnT), Electrochemiluminiscence (ECLIA), Cardiomyocytes (CMC), Peroxisomal proliferator activated receptor (PPARs), Reactive oxygen species (ROS).


A contact model based on the coefficient of restitution for simulations of bio-prosthetic heart valves.
A new general contact model is proposed for preventing inter-leaflet penetration of bio-prosthetic heart valves (BHV) at the end of the systole, which has the advantage of applying kinematic constraints directly and creating smooth free edges. At the end of each time step, the impenetrability constraints and momentum exchange between the impacting bodies are applied separately based on the coefficient of restitution. The contact method is implemented in a rotation-free, large deformation, and thin shell finite-element (FE) framework based on loop's subdivision surfaces. A nonlinear, anisotropic material model for a BHV is employed which uses Fung-elastic constitutive laws for in-plane and bending responses, respectively. The contact model is verified and validated against several benchmark problems. For a BHV-specific validation, the computed strains on different regions of a BHV under constant pressure are compared with experimentally measured data. Finally, dynamic simulations of BHV under physiological pressure waveform are performed for symmetrical and asymmetrical fiber orientations incorporating the new contact model and compared with the penalty contact method. The proposed contact model provides the coaptation area of a functioning BHV during the closing phase for both of the fiber orientations. Our results show that fiber orientation affects the dynamic of leaflets during the opening and closing phases. A swirling motion for the BHV with asymmetrical fiber orientation is observed, similar to experimental data. To include the fluid effects, fluid-structure interaction (FSI) simulation of the BHV is performed and compared to the dynamic results.


Prevalence of glucose-6-phosphate dehydrogenase deficiency and sickle cell trait among blood donors in Riyadh.
Blood donation from glucose-6-phosphate dehydrogenase (G6PD)-deficient and sickle cell trait (SCT) donors might alter the quality of the donated blood during processing, storage or in the recipient's circulatory system. The aim of this study was to determine the prevalence of G6PD deficiency and SCT among blood donors coming to King Khalid University Hospital (KKUH) in Riyadh. It was also reviewed the benefits and risks of transfusing blood from these blood donors. This cross-sectional study was conducted on 1150 blood samples obtained from blood donors that presented to KKUH blood bank during the period April 2006 to May 2006. All samples were tested for Hb-S by solubility test, alkaline gel electrophoresis; and for G6PD deficiency, by fluorescent spot test. Out of the 1150 donors, 23 (2%) were diagnosed for SCT, 9 (0.78%) for G6PD deficiency and 4 (0.35%) for both conditions. Our prevalence of SCT and G6PD deficiency is higher than that of the general population of Riyadh. We recommend to screen all units for G6PD deficiency and sickle cell trait and to defer donations from donors with either of these conditions, unless if needed for special blood group compatibility, platelet apheresis or if these are likely to affect the blood bank inventory. If such blood is to be used, special precautions need to be undertaken to avoid complications in high-risk recipients.


Generalized Eddington analytical model for azimuthally dependent radiance simulation in stratified media.
A fast analytical radiative transfer model to account for propagation of unpolarized monochromatic radiation in random media with a plane-parallel geometry is presented. The model employs an Eddington-like approach combined with the delta phase-function transformation technique. The Eddington approximation is extended in a form that allows us to unfold the azimuthal dependence of the radiance field. A first-order scattering correction to the azimuth-dependent Eddington radiative model solution is also performed to improve the model accuracy for low-scattering media and flexibility with respect to use of explicit arbitrary phase functions. The first-order scattering-corrected solution, called the generalized Eddington radiative model (GERM), is systematically tested against a numerical multistream discrete ordinate model for backscattered radiance at the top of the medium. The typical mean accuracy of the GERM solution is generally better than 10% with a standard deviation of 20% for radiance calculations over a wide range of independent input optical parameters and observation angles. GERM errors are shown to be comparable with the errors due to an input parameter uncertainty of precise numerical models. The proposed model can be applied in a quite arbitrary random medium, and the results are appealing in all cases where speed, accuracy, and/or closed-form solutions are requested. Its potentials, limitations, and further extensions are discussed.


Association of adiponectin gene variations with risk of incident myocardial infarction and ischemic stroke: a nested case-control study.
Adiponectin (ADIPOQ) gene variations are associated with risk of cardiovascular disease in patients with diabetes. No prospective data are available, however, on the risk of atherothrombotic disorders in persons with ADIPOQ variations who do not have diabetes. From a group of DNA samples collected at baseline in a prospective cohort of 14 916 initially healthy American men, we assessed the presence of 5 ADIPOQ genetic variants (rs266729, rs182052, rs822396, rs2241766, and rs1501299) in samples from 600 Caucasian men who subsequently suffered an atherothrombotic event (incident myocardial infarction or ischemic stroke) and from 600 age- and smoking-matched Caucasian men who remained free of reported vascular disease during follow-up (controls). Genotype distributions for the variations tested were in Hardy-Weinberg equilibrium. Marker-by-marker conditional logistic regression analysis, adjusted for potential risk factors, showed an association of rs266729 [recessive: odds ratio (OR), 0.26; 95% confidence interval (CI), 0.10-0.64; P=0.004] and rs182052 (recessive: OR, 0.40; 95% CI, 0.21-0.76; P=0.006) with decreased risk of ischemic stroke. These findings remained significant after Bonferroni correction. Haplotype-based (constituted by rs266729, rs182052, and rs822396) conditional logistic regression analysis, adjusted for the same potential risk factors, showed an association of haplotype G-A-G (OR, 0.28; 95% CI, 0.09-0.87; P=0.03) with decreased risk of ischemic stroke. Prespecified analysis limited to participants without baseline diabetes showed similar significant findings. The present prospective investigation provides further evidence for a protective role of adiponectin gene variation in the risk of ischemic stroke that was independent of the presence of diabetes.


Urinary 8-epi-PGF2alpha and its endogenous beta-oxidation products (2,3-dinor and 2,3-dinor-5,6-dihydro) as biomarkers of total body oxidative stress.
Although measurements of plasma F2-isoprostanes are established markers of oxidative stress, their quantification only reflects acute non-enzymatic lipid peroxidation. In this study, a new approach is described for the rapid isolation and measurement of urinary 8-epi-PGF2alpha and its endogenous beta-oxidation metabolites (2,3-dinor-8-epi-PGF2alpha and 2,3-dinor-5,6-dihydro-PGF2alpha) for use as index of total body oxidative stress. Isoprostanes were partitioned with ethyl acetate and subsequently purified by chromatography on an aminopropyl (NH2) and silica (Si) cartridge. Final analysis of F2-isoprostanes as trimethylsilyl-ester/pentafluorobenzyl ester derivatives was carried out by stable isotope dilution mass spectrometry. Overall recovery of F2-isoprostanes was 80+/-4%. Inter- and intra-assay coefficients of variation were 5% and 7%, respectively. In a group of healthy humans, the mean excretion rates expressed as nmol/mmol creatinine for 2,3-dinor-8-epi-PGF2alpha, 2,3-dinor-5,6-dihydro-8-epi-PGF2alpha, and 8-epi-PGF2alpha were 5.43+/-1.93, 2.16+/-0.71, and 0.36+/-0.16, respectively. Correlations were obtained between 8-epi-PGF2alpha and 2,3-dinor-8-epi-PGF2alpha or 2,3-dinor-5,6-dihydro-8-epi-PGF2alpha (r=0.998 and r=0.937, respectively). A strong relationship was also seen between 2,3-dinor-8-epi-PGF2 and 2,3-dinor-5,6-dihydro-8-epi-PGF2alpha (r=0.949). The new technique allows for high sample throughput and avoids the need for HPLC and/or other expensive equipment required for the initial sample preparation. Simultaneous analysis of urinary 8-epi-PGF2alpha and its metabolites should provide unique tool in clinical trials exploring the role of oxidant injury in human disease.


Chronic complications after cholecystojejunostomy.
Creation of a cholecystojejunostomy has been recommended as one option in the palliation of biliary obstruction due to pancreatic carcinoma. In these patients, an anastomosis is created between the gallbladder and jejunum, providing an alternate route for bile drainage when the distal common bile duct is occluded secondary to carcinoma in the head of the pancreas. Complications due to the procedure have rarely been reported. We present the case of a patient who had a cholecystojejunostomy for chronic pancreatitis 8 yr prior to presentation. Subsequent complications--including chronic cholecystitis, gastrointestinal bleeding, multiple recurrent hepatic and brain abscesses, and anastomotic varices--are reported. The literature on acute and chronic complications of this procedure is reviewed.


TeamWATCH: Visualizing development activities using a 3-D city metaphor to improve conflict detection and team awareness.
The awareness of others' activities has been widely recognized as essential in facilitating coordination in a team among Computer-Supported Cooperative Work communities. Several field studies of software developers in large software companies such as Microsoft have shown that coworker and artifact awareness are the most common information needs for software developers; however, they are also two of the seven most frequently unsatisfied information needs. To address this problem, we built a workspace awareness tool named TeamWATCH to visualize developer activities using a 3-D city metaphor. In this paper, we discuss the importance of awareness in software development, review existing workspace awareness tools, present the design and implementation of TeamWATCH, and evaluate how it could help detect and resolve conflicts earlier and better maintain group awareness via a controlled experiment. The experimental results showed that the subjects using TeamWATCH performed significantly better with respect to early conflict detection and resolution.


Broad cross-protection against H5N1 avian influenza virus infection by means of monoclonal antibodies that map to conserved viral epitopes.
Passive immunization with human H5 antisera or H5-specific monoclonal antibodies (MAbs) has potential as an effective treatment for acute H5N1 influenza virus infection, but its efficacy against antigenically diverse H5N1 viruses is unconfirmed. Cross-protection against antigenically diverse H5N1 strains with H5-specific MAbs, generated by successive immunization of antigenically distinct strains, was evaluated in mice. A panel of 52 broadly cross-reactive H5 specific MAbs were generated and characterized. One of these MAbs, 13D4, has been demonstrated to protect mice against lethal challenge by 4 H5N1 strains representing the current major genetic populations, clades 1, 2.1, 2.2, and 2.3, even at a stage of infection when H5N1 virus has disseminated beyond the pulmonary system. Complete neutralization of virus in lung tissue of infected animals was observed 24 h after treatment with 13D4. Mapping of this MAb with escape mutants showed it to bind to 2 conserved, possibly critical, sites of H5N1 hemagglutinin, 152 and 182. Generation of broadly cross-protective MAbs against H5N1 influenza virus may be optimized by selecting MAbs that target conserved sites in hemagglutinin. H5 MAbs such as 13D4 may prove to have therapeutic value in controlling infection due to current and future H5N1 variants.


Changes in mitochondrial electron transport chain activity during insect metamorphosis.
The midgut of the tobacco hornworm (Manduca sexta) is a highly aerobic tissue that is destroyed by programmed cell death during larval-pupal metamorphosis. The death of the epithelium begins after commitment to pupation, and the oxygen consumption of isolated midgut mitochondria decreases soon after commitment. To assess the role of the electron transport chain in this decline in mitochondrial function, the maximal activities of complexes I-IV of the respiratory chain were measured in isolated midgut mitochondria. Whereas there were no developmental changes in the activity of complex I or III, activities of complexes II and IV [cytochrome c oxidase (COX)] were higher in mitochondria from precommitment than postcommitment larvae. This finding is consistent with a higher rate of succinate oxidation in mitochondria isolated from precommitment larvae and reveals that the metamorphic decline in mitochondrial respiration is due to the targeted destruction or inactivation of specific sites within the mitochondria, rather than the indiscriminate destruction of the organelles. The COX turnover number (e- x s(-1) x cytochrome aa3(-1)) was greater for the enzyme from precommitment than postcommitment larvae, indicating a change in the enzyme structure and/or its lipid environment during the early stages of metamorphosis. The turnover number of COX in the intact mitochondria (in organello COX) was also lower in postcommitment larvae. In addition to changes in the protein or membrane phospholipids, the metamorphic decline in this rate constant may be a result of the observed loss of endogenous cytochrome c.


Hair follicle nevus in a distribution following Blaskho's lines.
We present a case of a rare follicular hamartoma, a hair follicle nevus. Although most previous reports have been solitary lesions, the case we are reporting had multiple papules and nodules following Blaskho's lines. There have been no reports of malignancies arising in these hamartomas.


Alterations to the Gut Microbiota and Their Correlation With Inflammatory Factors in Chronic Kidney Disease.
Alterations to the gut microbiota have been previously suggested to be tightly linked to chronic systemic inflammation, which is a major contributing factor to complications and disease progression in chronic kidney disease (CKD). Nevertheless, the effect of gut dysbiosis on the pathogenesis and/or production of inflammatory factors in CKD has not been extensively studied to date. In the present study, we conducted 16S ribosomal DNA pyrosequencing using fecal microbiota samples and analyzed the production of serum inflammatory factors in 50 patients with CKD and 22 healthy control (HC) subjects. The results revealed that compared to the HC subjects, patients with CKD exhibited a significant reduction in the richness and structure of their fecal microbiota. At the phylum level, compared to the HC group, patients with CKD also presented reduced abundance of Actinobacteria but increased abundance of Verrucomicrobia. Moreover, the genera Lactobacillus, Clostridium IV, Paraprevotella, Clostridium sensu stricto, Desulfovibrio, and Alloprevotella were enriched in the fecal samples of patients with CKD, while Akkermansia and Parasutterella were enriched in those of the HC subjects. The abundance of Akkermansia in the CKD group was significantly lower than that in the HC group (3.08 vs. 0.67%); this decrease in the abundance of Akkermansia, an important probiotic, in patients with CKD is a striking discovery as it has not been previously reported. Finally, we analyzed whether these changes to the fecal microbiota correlated with CKD clinical characteristics and/or the production of known inflammatory factors. Altered levels of the microbiota genera Parasutterella, Lactobacillus, Paraprevotella, Clostridium sensu stricto, and Desulfovibrio were shown to be correlated with CKD disease-severity indicators, including the estimated glomerular filtration rate. Most notably, Akkermansia was significantly negatively correlated with the production of interleukin-10. The results of the present study suggest that microbiota dysbiosis may promote chronic systemic inflammation in CKD. Furthermore, they support that modifying the gut microbiota, especially Akkermansia, may be a promising potential therapeutic strategy to attenuate the progression of, and/or systemic inflammation in, CKD.


Two-dimensional halide perovskite lateral epitaxial heterostructures.
Epitaxial heterostructures based on oxide perovskites and III-V, II-VI and transition metal dichalcogenide semiconductors form the foundation of modern electronics and optoelectronics1-7. Halide perovskites-an emerging family of tunable semiconductors with desirable properties-are attractive for applications such as solution-processed solar cells, light-emitting diodes, detectors and lasers8-15. Their inherently soft crystal lattice allows greater tolerance to lattice mismatch, making them promising for heterostructure formation and semiconductor integration16,17. Atomically sharp epitaxial interfaces are necessary to improve performance and for device miniaturization. However, epitaxial growth of atomically sharp heterostructures of halide perovskites has not yet been achieved, owing to their high intrinsic ion mobility, which leads to interdiffusion and large junction widths18-21, and owing to their poor chemical stability, which leads to decomposition of prior layers during the fabrication of subsequent layers. Therefore, understanding the origins of this instability and identifying effective approaches to suppress ion diffusion are of great importance22-26. Here we report an effective strategy to substantially inhibit in-plane ion diffusion in two-dimensional halide perovskites by incorporating rigid π-conjugated organic ligands. We demonstrate highly stable and tunable lateral epitaxial heterostructures, multiheterostructures and superlattices. Near-atomically sharp interfaces and epitaxial growth are revealed by low-dose aberration-corrected high-resolution transmission electron microscopy. Molecular dynamics simulations confirm the reduced heterostructure disorder and larger vacancy formation energies of the two-dimensional perovskites in the presence of conjugated ligands. These findings provide insights into the immobilization and stabilization of halide perovskite semiconductors and demonstrate a materials platform for complex and molecularly thin superlattices, devices and integrated circuits.


Mixed sugar-core-phosphate chelation of D-fructose 1,6-bisphosphate with the Re(V)O(tmen) metal fragment.
Sugar phosphates provide metal-binding sites both at their sugar core and at their phosphate group(s). Mixed sugar-core-phosphate chelation has been considered as a typical bonding mode within the physiological pH range for the central metabolite D-fructose 1,6-bisphosphate. The Re(V)O(tmen) metal fragment was used to enrich this coordination type. The formation of the [ReO(tmen)(Fruf2,3H-21,6P2H2-κ(3)O(2,3,P1))](-) monoanion was determined by NMR spectroscopy and mass spectrometry. The model compound rac-glycerol 1-phosphate yielded similar results in terms of NMR spectroscopy. Crystal-structure analyses of [ReO(tmen)(rac-Glyc2,3H-21PH-κ(3)O(2,3,P))]·2H2O and [ReO(phen)(rac-Glyc2,3H-21PH-κ(3)O(2,3,P))]·MeOH confirmed the coordination pattern.


Purkinje cells signal hand shape and grasp force during reach-to-grasp in the monkey.
The cerebellar cortex and nuclei play important roles in the learning, planning, and execution of reach-to-grasp and prehensile movements. However, few studies have investigated the signals carried by cerebellar neurons during reach-to-grasp, particularly signals relating to target object properties, hand shape, and grasp force. In this study, the simple spike discharge of 77 Purkinje cells was recorded as two rhesus monkeys reached and grasped 16 objects. The objects varied systematically in volume, shape, and orientation and each was grasped at five different force levels. Linear multiple regression analyses showed the simple spike discharge was significantly modulated in relation to objects and force levels. Object related modulation occurred preferentially during reach or early in the grasp and was linearly related to grasp aperture. The simple spike discharge was positively correlated with grasp force during both the reach and the grasp. There was no significant interaction between object and grasp force modulation, supporting previous kinematic findings that grasp kinematics and force are signaled independently. Singular value decomposition (SVD) was used to quantify the temporal patterns in the simple spike discharge. Most cells had a predominant discharge pattern that remained relatively constant across object grasp dimensions and force levels. A single predominant simple spike discharge pattern that spans reach and grasp and accounts for most of the variation (>60%) is consistent with the concept that the cerebellum is involved with synergies underlying prehension. Therefore Purkinje cells are involved with the signaling of prehension, providing independent signals for hand shaping and grasp force.


[Polio victims in Norway. Results of a national study 1994].
"The Norwegian Polio Study 1994" was conducted in order to survey the medical and social situation and the needs of polio victims. A questionnaire consisting of 133 questions with subquestions was sent to a total of 2,392 polio victims in Norway. 1,449 persons responded, of whom 66% were between 45 and 64 years of age. When specifying new health problems, between 55% and 85% stated that they had experienced increasing weakness of the muscles affected by polio, weakness in previously non-affected muscles, fatigue, intolerance to cold and/or pain in muscles and joints. Only 17% were satisfied with the public health services for polio victims. On the other hand, 67% of those who had undergone a comprehensive evaluation and had been treated at a central hospital were satisfied. The study indicates an obvious need to build up expertise in multidisciplinary evaluation and treatment of post-polio victims.


Ectopic Male Breast Cancer: A Case Report.
Carcinoma of male breast constitutes 1% of total breast malignancy. Carcinoma arising from ectopic breast tissue in male is an extremely rare entity and can be misdiagnosed. Ectopic breast tissue may be supernumerary or aberrant one. Despite morphologic difference, ectopic breast tissue presents characteristics analogous to orthoptic breast in terms of functional and pathologic degeneration. Most of the ectopic breast tissue occurs in thoracic or abdominal portion of milk line. If found in a location outside the milk line, it proves a diagnostic dilemma. We are reporting a case of 60-year-old male who presented with a fixed mass of size 10cm×8cm, in right chest wall infraclavicular area of 6 months duration. Histopathology of the mass revealed invasive duct carcinoma. He had no evidence of malignant or occult primary lesion in the bilateral mammary glands. Due to the paucity of the literature, incidence of ectopic male breast cancer and its management is not well understood. There is high probability of misdiagnosis of this disease. To the best of our knowledge this is the first described case of ectopic male breast cancer in the chest wall, not along the milk line, which is being reported here for documentation.


Redefining Cardiovascular Health to Include Sleep: Prospective Associations With Cardiovascular Disease in the MESA Sleep Study.
Background Although sufficient and healthy sleep is inversely associated with cardiovascular disease (CVD) and its risk factors, the American Heart Association's Life's Simple 7 (LS7), as a measure of cardiovascular health (CVH), did not include sleep. We evaluated an expanded measure of CVH that includes sleep as an eighth metric in relation to CVD risk. Methods and Results The analytic sample consisted of MESA (Multi-Ethnic Study of Atherosclerosis) Sleep Study participants who had complete data on sleep characteristics from overnight polysomnography, 7-day wrist actigraphy, validated questionnaires, and the outcome. We computed the LS7 score and 4 iterations of a new CVH score: score 1 included sleep duration, score 2 included sleep characteristics linked to CVD in the literature (sleep duration, insomnia, daytime sleepiness, and obstructive sleep apnea), scores 3 and 4 included sleep characteristics associated with CVD in MESA (score 3: sleep duration and efficiency, daytime sleepiness, and obstructive sleep apnea; score 4: score 3+sleep regularity). Multivariable-adjusted logistic and Cox proportional hazards models evaluated associations of the LS7 and CVH scores 1 to 4 with CVD prevalence and incidence. Among 1920 participants (mean age: 69±9 years; 54% female), there were 95 prevalent CVD events and 93 incident cases (mean follow-up, 4.4 years). Those in the highest versus lowest tertile of the LS7 score and CVH scores 1 to 4 had up to 80% lower odds of prevalent CVD. The LS7 score was not significantly associated with CVD incidence (hazard ratio, 0.62 [95% CI, 0.37-1.04]). Those in the highest versus lowest tertile of CVH score 1, which included sleep duration, and CVH score 4, which included multidimensional sleep health, had 43% and 47% lower incident CVD risk (hazard ratio, 0.57 [95% CI, 0.33-0.97]; and hazard ratio, 0.53 [95% CI, 0.32-0.89]), respectively. Conclusions CVH scores that include sleep health predicted CVD risk in older US adults. The incorporation of sleep as a CVH metric, akin to other health behaviors, may enhance CVD primordial and primary prevention efforts. Findings warrant confirmation in larger cohorts over longer follow-up.


Mechanism of Lactiplantibacillus plantarum regulating Ca2+ affecting the replication of PEDV in small intestinal epithelial cells.
Porcine epidemic diarrhea virus (PEDV) mainly invades the small intestine and promotes an inflammatory response, eventually leading to severe diarrhea, vomiting, dehydration, and even death of piglets, which seriously threatens the economic development of pig farming. In recent years, researchers have found that probiotics can improve the intestinal microenvironment and reduce diarrhea. At the same time, certain probiotics have been shown to have antiviral effects; however, their mechanisms are different. Herein, we aimed to investigate the inhibitory effect of Lactiplantibacillus plantarum supernatant (LP-1S) on PEDV and its mechanism. We used IPEC-J2 cells as a model to assess the inhibitory effect of LP-1S on PEDV and to further investigate the relationship between LP-1S, Ca2+, and PEDV. The results showed that a divalent cation chelating agent (EGTA) and calcium channel inhibitors (Bepridil hydrochloride and BAPTA-acetoxymethylate) could inhibit PEDV proliferation while effectively reducing the intracellular Ca2+ concentration. Furthermore, LP-1S could reduce PEDV-induced loss of calcium channel proteins (TRPV6 and PMCA1b), alleviate intracellular Ca2+ accumulation caused by PEDV infection, and promote the balance of intra- and extracellular Ca2+ concentrations, thereby inhibiting PEDV proliferation. In summary, we found that LP-1S has potential therapeutic value against PEDV, which is realized by modulating Ca2+. This provides a potential new drug to treat PEDV infection.


p16, p21, and p53 proteins play an important role in development of pancreatic intraepithelial neoplastic.
Deregulation of cell cycle takes place during the development of many cancers as well as pancreatic ductal adenocarcinoma (PDA), which develops from precursor lesions, most frequently including pancreatic intraepithelial neoplasia (PanIN). The aim of this study was to evaluate and compare the expression of p16, p21, and p53 proteins taking part in the regulation of the cell cycle in normal pancreatic ducts and pancreatic intraepithelial neoplasia at its various advancing stages. The expressions of p16, p21, and p53 were assessed immunohistochemically in 70 patients with different pancreatic diseases (pancreatic ductal adenocarcinoma, pancreatitis, and pancreatic cysts), showing also pancreatic intraepithelial neoplasia. The results correlated with chosen clinicopathological parameters. Our study revealed a difference in p16, p21, and p53 expressions between normal pancreatic ducts and various stages of PanIN. p16 expression progressively decreased, whereas p21 and p53 increased from normal pancreas to PanIN 1, 2, and 3. The expression of p21 was associated with age, p53 with PanIN location in the pancreas and p16 with the type of primary diseases. Simultaneously, we observed a directly proportional relationship between the expression of p21 and p53 proteins and inversely proportional between the p16 and the p21 and p53 proteins. p16, p21, and p53 proteins play an important role in the deregulation of the cell cycle and participate in the development of pancreatic intraepithelial neoplasia. Immunohistochemical evaluation of their expressions may be helpful in the diagnosis of PanIN.


Plasma 3,4-dihydroxyphenylethyleneglycol and 3-methoxy-4-hydroxyphenylethyleneglycol as indicators of central noradrenergic activity. A comparative study on control subjects and depressed patients.
Animal studies have suggested interspecies differences in brain norepinephrine (NE) metabolism, especially with regard to the relative proportions of 3,4-dihydroxyphenylethyleneglycol (DOPEG) compared to 3-methoxy-4-hydroxyphenylethyleneglycol (MOPEG). In order to question the value of both glycol metabolites as peripheral indices of central noradrenergic activity, a comparative study of plasma DOPEG and MOPEG (measured by HPLC) related to depression, sex, age and diagnostic categories (DSM-III) was carried out on depressed and control subjects. In addition, two groups of 8 patients were randomly submitted to a desipramine 150 mg/day, or a metapramine 450 mg/day antidepressant treatment influencing the formation of DOPEG and MOPEG in a different way. The study did not demonstrate any difference between DOPEG and MOPEG for most of the experimental factors. We found also a significant positive correlation between plasma levels of DOPEG and MOPEG. Our results support the idea that each of these two biological indices can be used in the assessment of central noradrenergic activity.


Top-down control in contour grouping.
Human observers tend to group oriented line segments into full contours if they follow the Gestalt rule of 'good continuation'. It is commonly assumed that contour grouping emerges automatically in early visual cortex. In contrast, recent work in animal models suggests that contour grouping requires learning and thus involves top-down control from higher brain structures. Here we explore mechanisms of top-down control in perceptual grouping by investigating synchronicity within EEG oscillations. Human participants saw two micro-Gabor arrays in a random order, with the task to indicate whether the first (S1) or the second stimulus (S2) contained a contour of collinearly aligned elements. Contour compared to non-contour S1 produced a larger posterior post-stimulus beta power (15-21 Hz). Contour S2 was associated with a pre-stimulus decrease in posterior alpha power (11-12 Hz) and in fronto-posterior theta (4-5 Hz) phase couplings, but not with a post-stimulus increase in beta power. The results indicate that subjects used prior knowledge from S1 processing for S2 contour grouping. Expanding previous work on theta oscillations, we propose that long-range theta synchrony shapes neural responses to perceptual groupings regulating lateral inhibition in early visual cortex.


Growth hormone and low dose estrogen in Turner syndrome: results of a United States multi-center trial to near-final height.
A cardinal clinical feature of Turner syndrome (TS) is linear growth failure resulting in extreme short stature: the median adult height of untreated women with TS is 143 cm, 20 cm (8 in.) below that of the general female population. In the largest multicenter, randomized, long-term, dose-response study conducted in the United States, 232 subjects with TS received either 0.27 or 0.36 mg/kg.wk of recombinant human GH with either low dose ethinyl E2 or oral placebo. The study was placebo-controlled for both GH and estrogen for the first 18 months and remained placebo-controlled for estrogen for its duration. The near-final height of the 99 subjects whose bone age was at least 14 yr was 148.7 +/- 6.1 cm after 5.5 +/- 1.8 yr of GH started at a mean age of 10.9 +/- 2.3 yr; this represents an average increase of 1.3 +/- 0.6 SD scores from baseline (TS standard). Height was greater than 152.4 cm (60 in.) in 29% of subjects compared with the expected 5% of untreated patients. Mean near-final heights of subjects who received the lower GH dose, with or without estrogen, were 145.1 +/- 5.4 and 149.9 +/- 6.0 cm, respectively; those who received the higher GH dose with or without estrogen achieved mean near-final heights of 149.1 +/- 6.0 and 150.4 +/- 6.0 cm, respectively. Factors that most impacted outcome were younger age, lower bone age/chronological age ratio, lower body weight, and greater height SD score at study entry. This study demonstrates significant GH-induced improvement in height SD score, with correction of height to within the normal channels for a significant number of patients, and provides evidence of a GH dose-response effect. These data also indicate that early administration of estrogen, even at relatively low doses, does not improve gain in near-final height in patients with TS.


[Somatotropic axis and molecular markers of mineral metabolism in children undergoing chronic peritoneal dialysis].
Growth failure is one of the most relevant complications in children with chronic kidney disease (CKD). Among others, growth hormone (GH) resistance and bone mineral disorders have been identified as the most important causes of growth retardation. 1. To characterize bone mineral metabolism and growth hormone bio-markers in CKD children treated with chronic peritoneal dialysis (PD). 2. To evaluate height change with rhGH treatment. A longitudinal 12-month follow-up in prepuberal PD children. Tanner stage >1, nephrotic syndrome, genetic disorders, steroids, intestinal absorption disorders, endocrine disturbances, treatment with GH to the entry of the study. Demographic and anthropometric data were registered. FGF23, Klotho, VitD, IGF-1, IGFBP3, and GHBP were measured to evaluate mineral and growth metabolism. 15 patients, 7 male, age 6.9 ± 3.0 y were included. Time on PD was 14.33 ± 12.26 months. Height/age Z score at month 1 was -1.69 ± 1.03. FGF23 and Klotho: 131.7 ± 279.4 y 125.9 ± 24.2 pg/ml, respectively. 8 patients were treated with GH during 6-12 months, showing a non-significant increase in height/age Z-score during the treatment period. Bivariate analysis showed a positive correlation between Klotho and delta ZT/E, and between GHBP vs growth velocity index (p < .05). FGF23 values were high and Klotho values were reduced in children with CKD in PD, comparing to healthy children. Somatotropic axis variables were normal or elevated. rhGH tends to improve height and there is a positive correlation of GHBP and growth velocity in these children.


The Collaborative Lipid Research Clinics Program Family Study. IV. Familial associations of plasma lipids and lipoproteins.
Familial associations of total cholesterol, low density lipoprotein cholesterol, triglycerides, and very low density lipoprotein cholesterol were examined in a population-based random sample of 858 white and 73 black probands and their 4,027 white and 245 black relatives from nine North American Lipid Research Clinics. Correlations among biologic relatives were highly significant for total cholesterol and low density lipoprotein cholesterol and to a lesser extent for triglycerides and very low density lipoprotein cholesterol in whites. Correlations for spouses, however, were not significant, suggesting a stronger influence of genes than shared environment in the determination of these traits. Homogeneity of familial correlations across age strata, clinics, and racial groups was examined. In general, correlations were homogeneous across age strata and clinics, and there was no asymmetry in parent-offspring correlations by the sex of the parent or offspring. Racial differences in correlations were not significant except in four of 32 comparisons, with blacks showing weaker correlations than whites in those instances.


Large gastric lipoma.
Gastric lipoma is a rare benign tumor and seen in five percent of gastro-intestinal lipomas and accounts for less than one percent of all gastric tumors. Gastric lipomas are located submucosally and usually in antral region of Stomach. Computed tomography is considered as valuable tool in the diagnosis of gastrointestinal lipomas. Due to their relative rarity, gastric lipomas are often left out of the differential diagnosis for upper gastro-intestinal submucosal masses. We report a case of 70 year female that presented with upper abdominal pain since last two years. Abdominal Computed tomography revealed a large gastric lipoma in antral region. Patient refused for any surgical intervention due to old age. Patient was provided symptomatic treatment and was under regular followup.


An epidemiologic study comparing fetal exposure to tobacco smoke in three Southeast Asian countries.
The high prevalence of smoking in Southeast Asia (SEA) means pregnant women face exposure to tobacco smoke that may affect the health of their fetus. This study determined fetal exposure to tobacco smoke by meconium analysis for cotinine in 3 locations in SEA: Bulacan Province, Philippines (N=316), Bangkok, Thailand (N=106) and Singapore City (N=61). Maternal exposure to tobacco smoke was 71.1% (1.3% active; 69.8% passive) in Bulacan, 57.5% (0.9% active; 58.6% passive) in Bangkok and 54.1% (11.5% active; 42.0% passive) in Singapore. Fetal exposure to tobacco smoke (by meconium analysis) was 1.3% (Bulacan), 4.7% (Bangkok) and 13.1% (Singapore); however, a large proportion of infants who tested positive for cotinine (65%) were born to mothers who gave no history of either active or passive exposure to environmental tobacco smoke. Fetal exposure to tobacco smoke is a major health problem.


Treatment options for synchronous lung and esophagus tumors: A difficult decision to make.
Synchronous lung and esophageal carcinomas are rare clinical entities. Curative resection with lymph node dissection is the most optimal treatment approach for both tumors. However, due to the high potential risk of postoperative complications, the right approach is to make a patient-specific decision via a multidisciplinary approach at all stages. In this article, we present three cases of synchronous lung and esophageal tumors treated with different approaches due to their specific circumstances and discuss their pre-, intra-, and postoperative stages.


Impact of magnesium:calcium ratio on calcification of the aortic wall.
An inverse relationship between serum magnesium concentration and vascular calcification has been reported following observational clinical studies. Moreover, several studies have been suggesting a protective effect of magnesium on the vascular calcification. However, the exact mechanism remains elusive, and investigators have speculated among a myriad of potential actions. The effect of magnesium on calcification of the aortic wall is yet to be investigated. In the present study, the effects of magnesium and calcium on the metabolism of extracellular PPi, the main endogenous inhibitor of vascular calcification, were investigated in the rat aorta. Calcium and magnesium have antagonist effects on PPi hydrolysis in the aortic wall. Km and Ki values for PPi hydrolysis in rat aortic rings were 1.1 mmol/L magnesium and 32 μmol/L calcium, respectively, but ATP hydrolysis was not affected with calcium. Calcium deposition in the rat aortic wall dramatically increased when the magnesium concentration was increased (ratio of Mg:Ca = 1:1; 1.5 mmol/L calcium and 1.5 mmol/L magnesium) respect to low magnesium concentration (ratio Mg:Ca = 1:3, 1.5 mmol/L calcium and 0.75 mmol/L magnesium). Data from observational clinical studies showing that the serum magnesium concentration is inversely correlated with vascular calcification could be reinterpreted as a compensatory regulatory mechanism that reduces both PPi hydrolysis and vascular calcification. The impact of magnesium in vascular calcification in humans could be studied in association with calcium levels, for example, as the magnesium:calcium ratio.


Maternal expression of the checkpoint protein BubR1 is required for synchrony of syncytial nuclear divisions and polar body arrest in Drosophila melanogaster.
The spindle checkpoint is a surveillance mechanism that regulates the metaphase-anaphase transition during somatic cell division through inhibition of the APC/C ensuring proper chromosome segregation. We show that the conserved spindle checkpoint protein BubR1 is required during early embryonic development. BubR1 is maternally provided and localises to kinetochores from prophase to metaphase during syncytial divisions similarly to somatic cells. To determine BubR1 function during embryogenesis, we generated a new hypomorphic semi-viable female sterile allele. Mutant females lay eggs containing undetectable levels of BubR1 show early developmental arrest, abnormal syncytial nuclear divisions, defects in chromosome congression, premature sister chromatids separation, irregular chromosome distribution and asynchronous divisions. Nuclei in BubR1 mutant embryos do not arrest in response to spindle damage suggesting that BubR1 performs a checkpoint function during syncytial divisions. Furthermore, we find that in wild-type embryos BubR1 localises to the kinetochores of condensed polar body chromosomes. This localisation is functional because in mutant embryos, polar body chromatin undergoes cycles of condensation-decondensation with additional rounds of DNA replication. Our results suggest that BubR1 is required for normal synchrony and progression of syncytial nuclei through mitosis and to maintain the mitotic arrest of the polar body chromosomes after completion of meiosis.


Treatment of tumors of the third ventricle: a new and simple technique.
A new surgical technique is described for the treatment of benign cystic tumors of the third ventricle. It basically consist of: 1) introduction of a catheter to the third ventricle, therefore to the cyst; 2) suction of all the material of the cyst; 3) connection of the catheter to a ventriculoatrial shunt. A report of five patients with a possible colloid cyst in the third ventricle treated with this technique and the satisfactory results obtained in all the cases, with lack of morbidity and mortality, is presented. A comparison between the traditional surgical procedure and ours, as far as the technique itself and the results are concerned, is made. The simplicity of the technique is emphasized and it is proposed as another solution for the treatment of cystic tumors of the third ventricle.


Brain and liver fatty acid composition changes upon consumption of Lactobacillus rhamnosus LA68.
Recent reports suggest that the metabolic activity of the enteric microbiota may influence the fatty acid composition of the host tissue. There are many studies dealing with the influence of lactobacilli on various pathological conditions, and some of the effects are strain-specific. This study was designed to test the effects of a particular Lactobacillus strain, Lactobacillus rhamnosus LA68 on fatty acid composition of the liver and the brain of C57BL/6 mice in the absence of an underlying pathological condition. Female mice were supplemented with live L. rhamnosus LA68 bacteria for the duration of 1 month. Serum biochemistry was analyzed and liver and brain fatty acid composition was assessed by gas-liquid chromatography. Significant changes in liver and brain fatty acid composition were detected. In the liver tissue we detected an increase in palmitoleic acid (p = 0.038), while in the brain compartment we found an increase in palmitic (p = 0.042), stearic (p = 0.017), arachidonic acid (p = 0.009) and docosahexaenoic acid (p = 0.004) for control versus experimental group. These results show discrete changes caused by LA68 strain consumption. Even short duration of administration of LA68 influences the fatty acid composition of the host which adds to the existing knowledge about Lactobacillus host interaction, and adds to the growing knowledge of metabolic intervention possibilities.


Visual outcome and impact on quality of life after surgeries differ in children operated for unilateral and bilateral cataract (Pune study 2011).
We compared vision and quality of life (VQL) of children aged 5-15 years and operated for unilateral and bilateral cataract between 2008 and 2010 in western India. In this cohort study, ophthalmologists assessed vision, anterior and posterior segment of eyes with cataract. Children completed a functional vision questionnaire (LVP-FVQ). Follow up at 6 months after surgery included the best corrected visual acuity (BCVA), FVQ and eye assessment. The improvement of BCVA and quality of life were compared in group of unilateral and bilateral cataract. A total of 20 (70%) bilateral and 7 (39%) unilateral cataract were operated within 1 month of detection. All 48 eyes with bilateral cataract were congenital and 12 (67%) unilateral cataract were traumatic. Among bilateral group, 27 eyes [56.2% (95% confidence interval (CI) 44.4-72.2)] and in unilateral group 11 eyes [61.1% (95% CI 38.6-83.6)] had vision ≥ 20/60 at 6 months follow up. The visual gain was significantly higher in children who were operated between 1 month and 1 year of detection (adjusted Odds ratio (OR) = 15.6 P = 0.03). Positive impact on VQL in bilateral group was noted in 50%, 27%, and 13% children for subscale of distant vision, near vision, and field of vision, respectively. There was positive impact in these subscales among children with unilateral cataract. Thirty percent eyes with bilateral cataract and 22% of eyes with unilateral cataract improved their vision. Surgery within 1 month of cataract was significant predictor of improved vision (OR = 16.6 P = 0.02). Vision and VQL improved in children with unilateral and bilateral cataract. However, it was better 6 months following surgery in children with bilateral cataract than in children with unilateral cataract.


Effect of matrix elasticity on affinity binding and release of bioparticles. Elution of bound cells by temperature-induced shrinkage of the smart macroporous hydrogel.
The first step of bacterial or viral invasion is affinity and presumably multisite binding of bioparticles to an elastic matrix like a living tissue. We have demonstrated that model bioparticles such as inclusion bodies (spheres of about 1 microm in size) Escherichia coli cells (rods 1 x 3 microm), yeast cells (8 microm spheres), and synthetic microgel particles (0.4 microm spheres) are binding via different affinity interactions (IgG antibody-protein A, sugar-lectin, and metal ion-chelate) to a macroporous hydrogel (MH) matrix bearing appropriate ligands. The elastic deformation of the MH results in the detachment of affinity bound bioparticles. The particle detachment on elastic deformation is believed to be due to multipoint attachment of the particles to affinity matrix and the disturbance of the distance between affinity ligands when the matrix is deformed. No release of affinity bound protein occurred on elastic deformation. The efficiency of the particle release by the elastic deformation depends on the density of the ligands at the particle surface as well as on the elasticity of the matrix for relatively large particles. The release of the particles occurred irrespectively of whether the deformation was caused by external forces (mechanical deformation) or internal forces (the shrinkage of thermosensitive macroporous poly-N-isopropylacrylamide hydrogel on increase in temperature).


Higher Daily Physical Activities Continue to Preserve Muscle Strength After Mid-Life, But Not Muscle Mass After Age of 75.
The objective of this study is to explore the impact of aging and daily physical activities (PA) on muscle mass and muscle strength among community-dwelling people in Taiwan.The design is a cross-sectional study. Setting is a population-based community study.One thousand eight hundred thirty-nine community-dwelling people aged 50 years and older in Taiwan participated in the study.Measurements include demographic characteristics, Charlson Comorbidity Index (CCI) for multimorbidity, mini-nutritional assessment (MNA) for nutritional evaluation, functional autonomy measurement system (SMAF) for functional capacity, Chinese version mini mental state examination (MMSE), 5-item Taiwan Geriatric Depression Scale (TGDS-5), Chinese version of International Physical Activity Questionnaire (IPAQ), height-adjusted skeletal muscle index (SMI) by dual-energy X-ray absorptiometry, handgrip strength, timed 6-m walking test for usual gait speed. Laboratory measurements include testosterone, sex-hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEA-S), insulin-like growth factor-1 (IGF-1), high-sensitivity C-reactive protein (hsCRP), 25-OH vitamin D, and insulin resistance.After adjusted for age, the lowest PA tertile was associated with multimorbidity, poorer functional capacity and nutritional status, more depressive symptoms, lower SMI and lower handgrip strength, and lower free androgen index (FAI) in men. The negative association between PA and low SMI was more significant among subjects aged younger than 65 and the association decreased with older age. For subjects aged younger than 65, moderate daily PA (Q2) group had lower risk of low SMI compared with Q1 participants (OR: 0.62, 95% CI = 0.39-0.98, P = 0.040). For muscle strength, higher daily PA was associated with lower risk of low handgrip strength after age of 65 and the effect was dose-dependent. The effect was attenuated by potential confounders during age 65 to 74, while after age 75, the result was almost unchanged in fully adjusted model (OR = 0.37, 95% CI = 0.18-0.79, P = 0.010).Older age may attenuate the protective effects of higher daily PA on preventing muscle loss, but higher daily PA continues to preserve muscle strength at different age groups, even after the age of 75. The prognostic role of daily PA may be mediated by muscle strength instead of muscle mass among people aged 75 years and older.


Radiolabelled granulocytes in inflammatory bowel disease: diagnostic possibilities and clinical indications.
Radiolabelled granulocytes in chronic inflammatory bowel diseases (CIBD) are able to diagnose the disease extent and assess the disease activity. It may be performed with 111In oxine- and 99Tcm hexamethylpropyleneamineoxime (HMPAO)-labelled cells. The granulocyte scan localizes inflamed bowel segments with an accuracy comparable with radiology and endoscopy including biopsy of the bowel (r = 0.95; P less than 0.001). The specificity of the scan for diseased segments is near 100%, the sensitivity 92%. A three-phase white blood cell scan (imaging: 0.5, 4, 20 h post injection) allows differentiation of diseased bowel segments from abscesses and fistulas. False positive results are possible in necrotic carcinomas. The 99Tcm HMPAO scan shows rapid renal and delayed biliary and intestinal excretion of tracer. In this way diagnostic problems arise in the small pelvis. Because of the intestinal and biliary excretion, early images should be obtained (0.5-2 h post injection). Later scans with 99Tcm HMPAO are of minor importance. The disease activity can very specifically be assessed by the determination of the percentage faecal 111In excretion (96 h faecal collection). Active and non-active diseases can be clearly differentiated. We found no correlation with the subjectively influenced Crohn's disease activity index (CDAI) (r = 0.25; P greater than 0.05), but good correlations with the Dutch Index (van Hees: r = 0.67), ESR (r = 0.69), serum albumin (r = -0.54) and orosomucoid (r = 0.65). The percentage faecal excretion correlates well with the histologically estimated leucocytic bowel infiltration. Because of the intestinal 99Tcm HMPAO excretion the determination of faecal excretion is pointless in 99Tcm studies.(ABSTRACT TRUNCATED AT 250 WORDS)


Fossil alpha-recoil analysis of certain variant radioactive halos.
The distribution of alpha-radioactivity in the vicinity of uranium and of certain variant radioactive halos in biotite was investigated by the fossil alpharecoil method. Within the limits of the method I could not confirm a previously proposed hydrothermal mechanism for the origin of certain variant halo types due to polonium isotopes.


Coumarins as Modulators of the Keap1/Nrf2/ARE Signaling Pathway.
The Keap1/Nrf2/ARE system is a central defensive mechanism against oxidative stress which plays a key role in the pathogenesis and progression of many diseases. Nrf2 is a redox-sensitive transcription factor controlling a variety of downstream antioxidant and cytodefensive genes. Nrf2 has a powerful anti-inflammatory activity mediated via modulating NF-κB. Therefore, pharmacological activation of Nrf2 is a promising therapeutic strategy for the treatment/prevention of several diseases that are underlined by both oxidative stress and inflammation. Coumarins are natural products with promising pharmacological activities, including antioxidant, anticancer, antimicrobial, and anti-inflammatory efficacies. Coumarins are found in many plants, fungi, and bacteria and have been widely used as complementary and alternative medicines. Some coumarins have shown an ability to activate Nrf2 signaling in different cells and animal models. The present review compiles the research findings of seventeen coumarin derivatives of plant origin (imperatorin, visnagin, urolithin B, urolithin A, scopoletin, esculin, esculetin, umbelliferone, fraxetin, fraxin, daphnetin, anomalin, wedelolactone, glycycoumarin, osthole, hydrangenol, and isoimperatorin) as antioxidant and anti-inflammatory agents, emphasizing the role of Nrf2 activation in their pharmacological activities. Additionally, molecular docking simulations were utilized to investigate the potential binding mode of these coumarins with Keap1 as a strategy to disrupt Keap1/Nrf2 protein-protein interaction and activate Nrf2 signaling.


Molecular tools for isolate and community studies of Pyrenomycete fungi.
The Pyrenomycetes, defined physiologically by the formation of a flask-shaped fruiting body present in the sexual form, are a monophyletic group of fungi that consist of a wide diversity of populations including human and plant pathogens. Based on sequence analysis of 18S ribosomal DNA (rDNA), rDNA regions conserved among the Pyrenomycetes but divergent among other organisms were identified and used to develop selective PCR primers and a highly specific primer set. The primers presented here were used to amplify large portions of the 18S rDNA as well as the entire internal transcribed spacer (ITS) region (ITS 1, 5.8S rDNA, and ITS 2). In addition to database searches, the specificity of the primers was verified by PCR amplification of DNA extracted from pure culture isolates and by sequence analysis of fungal rDNA PCR-amplified from environmental samples. In addition, denaturing gradient gel electrophoresis (DGGE) analyses were performed on closely related Colletotrichum isolates serving as a model pathogenic genus of the Pyrenomycetes. Although both ITS and 18S rDNA DGGE analyses of Colletotrichum were consistent with a phylogeny established from sequence analysis of the ITS region, DGGE analysis of the ITS region was found to be more sensitive than DGGE analysis of the 18S rDNA. This study introduces molecular tools for the study of Pyrenomycete fungi by the development of two specific primers, demonstration of the enhanced sensitivity of ITS-DGGE for typing of closely related isolates and application of these tools to environmental samples.


[New arguments in favor of early extubation following surgical interventions on the heart].
An algorithm was introduced for simplification of postoperative treatment after cardiac operations which safely enables an early weaning from the ventilator and extubation. Using this algorithm consequently, the postoperative time of respirator treatment was reduced to an average 132 minutes in adults. The extubation could be performed an average 36 minutes later. In 121 patients with aortocoronary bypass grafts and 57 patients with valve replacements, extensive haemodynamic investigations based on the SWAN-GANZ-monitoring system showed that after weaning from the ventilator and extubation stabilisation occurred after a short period of instability. The data including arterial and mixed venous blood gases confirm that under the conditions of modern cardiac surgery a short postoperative respirator treatment is not only possible but necessary for avoiding cardiocirculatory and respiratory side-effects.


Detrimental effects of N(omega) nitro-L-arginine methyl ester (L-NAME)in experimental Escherichia coli sepsis in the newborn piglet.
The role of nitric oxide during neonatal sepsis is complex. We tested the hypothesis that nonselective inhibition of nitric oxide synthase with N(omega) -nitro-L-arginine methyl ester (L-NAME) is detrimental during the early phase of experimental sepsis in the newborn piglet. Newborn piglets were divided into four groups: 6 in the control group, 6 in the L-NAME control group, 12 in the sepsis group (SG), and 11 in the sepsis with L-NAME group (NS). Sepsis was induced by intravenous injection of 10(8) colony forming units of Escherichia coli. L-NAME 10 mg/kg was given intravenously 60 min before the induction of sepsis. The survival rate of piglets after 4 hr was 27% in NS, while it was 100% in other groups. Systemic hypotension, observed in both SG and NS, were more profound in NS. Leukopenia was observed in both SG and NS. Thrombocytopenia, prolongation of prothrombin time and activated partial thromboplastin time, and increase in thrombin-antithrombin complexes were observed only in NS. Decreased PaO2 /FiO2 ratio, arterial pH and base excess, and increased blood lactate levels observed in both SG and NS, but were more profound in NS. These findings suggest that nonselective inhibition of nitric oxide synthase with L-NAME is detrimental during the early phase of experimental neonatal sepsis.


Effects of narasin supplementation frequency on intake, ruminal fermentation parameters, and nutrient digestibility of Bos indicus Nellore steers fed with forage-based diets.
The study aimed to evaluate if the frequency of narasin supplementation impacts dry matter intake, ruminal fermentation parameters, and apparent digestibility of nutrient in Nellore (Bos indicus) steers fed forage-based diets. A total of 32 rumen-cannulated Nellore steers (initial body weight [BW] = 317 ± 27 kg; age =18 ± 1 mo) were assigned to individual pens in a randomized complete block design according to their initial shrunk BW. Within block, steers were randomly assigned to 1 of 4 treatments: 1) forage-based diet without the addition of narasin (CON; n = 8), 2) CON diet plus 13 ppm of narasin every 24 h (N24; n = 8), 3) CON diet plus 26 ppm of narasin every 48 hours (N48; n = 8), or 4) CON diet plus 39 ppm of narasin every 72 hours (N72; n = 8). The experimental period lasted 30 d, with 18 d for diet adaptation and 12 d for sample collection. The experimental diets contained 95% of Tifton-85 (Cynodon dactylon spp.) haylage and 5% ground corn used as a delivery vehicle for narasin. Ruminal fluid was obtained from d 25 to 30 at 6 h after feeding to determine ruminal fermentation parameters. Narasin supplementation frequency did not affect (P ≥ 0.22) nutrient intake and total tract apparent digestibility. Steers fed N24 and N48 had reduced (P = 0.02) ruminal acetate concentration compared with CON and N72. Daily supply of narasin increased (P = 0.01) the molar proportion of propionate compared with CON and N72, and it did not differ between N24 vs. N48, N48 vs. N72, and N72 vs. CON. Also, N48 steers had greater (P = 0.01) rumen propionate concentration compared with CON. The N24 treatment decreased the Ac:Prop (P = 0.01) and AcBut:Prop (P = 0.02) ratio compared with CON and N72, while N48 had reduced (P = 0.01) Ac:Prop and AcBut:Prop ratio when compared with CON steers. Steers fed N24 and N48 had greater (P = 0.04) ruminal short-chain fatty acids compared with CON, but it did not differ (P > 0.11) between N24, N48, and N72. Supplementing narasin to steers fed forage-based diets decreased (P < 0.01) ruminal ammonia concentration compared with CON steers regardless of supplementation frequency, being the least result observed for N24 steers. Collectively, narasin supplementation frequency affected fermentation parameters without altering the nutrient intake and total tract apparent digestibility. Hence, decreasing frequency of narasin supplementation to Nellore steers fed a forage-based diet did not reduce the capacity to modulate rumen fermentation parameters.


Handgrip strength and associated sociodemographic and lifestyle factors: A systematic review of the adult population.
The aim of this study was to identify studies on handgrip strength (HGS) and associations with sociodemographic variables and lifestyle in adults. Searches were performed in Scielo, PubMed, EBSCO, Lilacs, Scopus and Web of Science databases. Two blinded reviewers independently screened the articles, scored their methodological quality and extracted data. The selected studies were analyzed according to the agreement of their findings with the evidence summary. Overall, 18,038 studies were found and 26 articles were selected. Lower HGS levels were found in older individuals (n = 20), females (n = 13) and in those not engaged in physical activities (n = 5). Older adults, females, those of lower educational level and not physically active had lower HGS levels. The adoption of standardization in relation to specific cutoff points for HGS classification becomes necessary in order to allow better comparison of results.


Anxiety in candidates for radical prostatectomy in a university hospital.
Metabolic changes caused by anxiety can interfere in both the surgery itself and the recovery process. One way to reassure the patient is to clarify how the procedure will be performed and discuss the possible complications. This study aimed to investigate the anxiety level of candidates for radical prostatectomy at a university hospital. Thirty-four patients with a diagnosis of prostate cancer were studied prospectively. Data collection involved the administration of the Hospital Anxiety and Depression Scale and a radical prostatectomy knowledge test. The results showed that 94.1% of the patients reported having received clarifications from the physician or healthcare team regarding the surgery and 23.5% reported having received information on the probability of a medical error during surgery. The most cited postoperative complications were sexual impotence and urinary incontinence. A significant association was found between the total Hospital Anxiety and Depression Scale score and the complications cited (p=0.0004); patients who marked a larger number of possible complications had a higher Hospital Anxiety and Depression Scale score. The present study demonstrates that the explanations given by the multidisciplinary health team are not achieving their maximum potential in terms of lowering patient anxiety.


Parent-reported toilet training practices and the role of pediatric primary care providers.
Toilet training is a universal developmental milestone and a stressful period for families with few empirically based guidelines. This study identified currently used methods of toilet training and sources used for parental guidance. A descriptive, qualitative design was used. Participants included 479 parents of children aged 2-6 years. Parents described diverse toilet training strategies, most of which were behavioral and inconsistent with recommendations of the American Academy of Pediatrics. Most children were toilet trained between 24 and 36 months within 5 weeks. Forty-one percent of parents relied on the Internet for toilet training information, and fewer than half reported involvement of their child's primary care provider. Parents in the community would likely benefit from additional education and anticipatory guidance from primary care providers about normative toilet training. Further work is needed to understand the effectiveness of different methods of training and improve adherence to AAP recommendations.


De novo design of buttressed loops for sculpting protein functions.
In natural proteins, structured loops play central roles in molecular recognition, signal transduction and enzyme catalysis. However, because of the intrinsic flexibility and irregularity of loop regions, organizing multiple structured loops at protein functional sites has been very difficult to achieve by de novo protein design. Here we describe a solution to this problem that generates structured loops buttressed by extensive hydrogen bonding interactions with two neighboring loops and with secondary structure elements. We use this approach to design tandem repeat proteins with buttressed loops ranging from 9 to 14 residues in length. Experimental characterization shows the designs are folded and monodisperse, highly soluble, and thermally stable. Crystal structures are in close agreement with the computational design models, with the loops structured and buttressed by their neighbors as designed. We demonstrate the functionality afforded by loop buttressing by designing and characterizing binders for extended peptides in which the loops form one side of an extended binding pocket. The ability to design multiple structured loops should contribute quite generally to efforts to design new protein functions.


Modeling hepatitis C virus protein and p53 interactions in hepatocytes: Implications for carcinogenesis.
Hepatitis C virus (HCV) infection has reached epidemic proportions worldwide. Individuals with chronic HCV infection and without access to treatment are at high risk for developing hepatocellular carcinoma (HCC), a liver cancer that is rapidly fatal after diagnosis. A number of factors have been identified that contribute to HCV-driven carcinogenesis such as scarring of the liver, and chronic inflammation. Recent evidence indicates a direct role for HCV-encoded proteins themselves in oncogenesis of infected hepatocytes. The viral protein HCV core has been shown to interact directly with the host tumor suppressor protein p53, and to modulate p53-activity in a biphasic manner. Here, biochemically-motivated mathematical models of HCV-p53 interactions are developed to elucidate the mechanisms underlying this phenomenon. We show that by itself, direct interaction between HCV core and p53 is insufficient to recapitulate the experimental data. We postulate the existence of an additional factor, activated by HCV core that inhibits p53 function. We present experimental evidence in support of this hypothesis. The model including this additional factor reproduces the experimental results, validating our assumptions. Finally, we investigate what effect HCV core-p53 interactions could have on the capacity of an infected hepatocyte to repair damage to its DNA. Integrating our model with an existing model of the oscillatory response of p53 to DNA damage predicts a biphasic relationship between HCV core and the transformative potential of infected hepatocytes. In addition to providing mechanistic insights, these results suggest a potential biomarker that could help in identifying those HCV patients most at risk of progression to HCC.


Stochastic reconstruction of anisotropic polarizabilities.
By solving a linear stochastic equation, we demonstrate how probability density functions of scattered intensities and order statistics can be used for reconstructing the statistical properties of fluctuating anisotropic polarizabilities. Depending on the statistical relationship between the elements of the polarizability tensor, we show how task optimized measurements can be conducted to reduce the number of necessary measurements. This approach is directly applicable to polarimetric measurements with limited control over the experimental conditions.


Impact of E-cig aerosol vaping on fetal and neonatal respiratory development and function.
Electronic cigarette (e-cig) use has increased over the past decade, and exposure to e-cig aerosols during pregnancy raises concern for maternal and fetal health. The developing fetal lung is known to be sensitive to prenatal tobacco product exposure. Utilizing a 3-pronged approach, we examined the effects of prenatal e-cig aerosols with, and without nicotine on respiratory development in a murine model. RNAseq analysis of fetal lungs revealed extensive dysregulation in gene expression. Morphologic assessment of distal airspaces in neonatal lungs display an emphysematic phenotype. Respiratory mechanics of neonates display signs of increased respiratory workload, with increased resistance and decreased compliance. These data are novel and provide evidence that prenatal e-cig exposure may result in altered lung function or development of disease.


The Prevention of Musculoskeletal Complaints in Instrumental Musicians: A Systematic Review.
This systematic review synthesizes the evidence of various interventions aiming to prevent muscu¬loskeletal complaints in professional musicians. This study comprises a systematic review according to PRISMA guidelines. A database search was performed in Cochrane, Embase, and PubMed on 13 September 2022 without time and language restrictions. The search consisted of the following groups of keywords: preventive measures AND musculoskeletal AND musicians. Risk of bias was assessed with the PEDro and MINORs criteria. Two reviewers independently selected and assessed the quality of the studies. A total of 1,831 articles were screened and 20 articles were included in this review. There is a wide range of interventions aiming to reduce musculoskeletal complaints in musicians. Among the studied programs were interventions focused on strength, cardiovascular and general fitness, flexibility as well as educational interventions and combinations of these. On average, scientific quality was good, moderate, and low for randomized controlled trials (RCTs), comparative studies, and non-comparative studies, respectively. A significant beneficial effect of the evaluated intervention on either playing-related musculoskeletal disorders (PRMD) frequency or severity or (playing-related) pain frequency and intensity was reported in at least 12 of the 20 studies. In particular, interventions with a strength training program reported a beneficial effect on PRMD frequency and severity as well as pain intensity and interference on the short-term. This systematic review highlights the heterogeneity in interventions aiming to prevent musculoskeletal complaints in musicians. Strength training might have a positive short-term effect on reducing musculoskeletal complaints. There is a need for further research to improve the quality of evidence as well as long-term outcomes of injury prevention programs.


Characterization of Epichloë coenophiala within the US: are all tall fescue endophytes created equal?
Tall fescue (Lolium arundinaceum) is a valuable and broadly adapted forage grass that occupies approximately 14 million hectares across the United States. A native to Europe, tall fescue was likely introduced into the US around the late 1800's. Much of the success of tall fescue can be attributed to Epichloë coenophiala (formerly Neotyphodium coenophialum) a seed borne symbiont that aids in host persistence. Epichloë species are capable of producing a range of alkaloids (ergot alkaloids, indole-diterpenes, lolines, and peramine) that provide protection to the plant host from herbivory. Unfortunately, most tall fescue within the US, commonly referred to as "Kentucky-31" (KY31), harbors the endophyte E. coenophiala that causes toxicity to grazing livestock due to the production of ergot alkaloids. Molecular analyses of tall fescue endophytes have identified four independent associations, representing tall fescue with E. coenophiala, Epichloë sp. FaTG-2, Epichloë sp. FaTG-3, or Epichloë sp. FaTG-4. Each of these Epichloë species can be further distinguished based on genetic variation that equates to differences in the alkaloid gene loci. Tall fescue samples were evaluated using markers to simple sequence repeats (SSRs) and alkaloid biosynthesis genes to determine endophyte strain variation present within continental US. Samples represented seed and tillers from the Suiter farm (Menifee County, KY), which is considered the originating site of KY31, as well as plant samples collected from 14 states, breeder's seed and plant introduction lines (National Plant Germplasm System, NPGS). This study revealed two prominent E. coenophiala genotypes based on presence of alkaloid biosynthesis genes and SSR markers and provides insight into endophyte variation within continental US across historical and current tall fescue samples.


The effects of obesity on orthopaedic foot and ankle pathology.
It is believed that obese individuals may have an increased number of foot and ankle problems. The World Health Organization recommends a standard classification of adult overweight and obesity using the following body mass index (BMI) calculations: a BMI of 25.0 to 29.9 kg per m(2) is defined as overweight; a BMI of 30.0 kg per m(2) or more is defined as obesity. The purpose of this paper was to report a survey of 1411 patients in an orthopaedic foot and ankle practice and compare the incidence of orthopaedic foot and ankle complaints with the BMI. One thousand four hundred and eleven adults, including 887(62.4%) women and 535(37.6%) men, were evaluated in this study. The BMI was calculated for each subject using the standards of the World Health Organization. The subjects were divided into two groups: normal and overweight. The normal weight subjects had a BMI of 18.5 to 24.9 (n = 684; 48.1%) and the overweight or obese group had a BMI greater than or equal to 25 (n = 738; 51.9%). In this study, being overweight or obese significantly increased the chances of having tendinitis in general. If the subjects were overweight or obese, there was an increased likelihood, although not significant, of plantar fasciitis and osteoarthritis. If the individuals were of normal weight, there was an increased likelihood of hallux valgus. Tendinitis, plantar fasciitis, and osteoarthritis usually are secondary to overuse and increased stress on the soft tissues and joints, which may be directly related to increased weight on these structures.


Identification of a potentially radiosensitive subgroup among patients with breast cancer.
The description of genes and genetic syndromes, such as ataxia-telangiectasia, that predispose some women to breast cancer will provide greater insight into the genetic basis of cancer susceptibility. Our goal was to establish cell lines from patients with breast and bladder cancers, to screen for enhanced levels of radiation-induced arrest in the G2 phase of the cell cycle such as is observed in ataxia-telangiectasia heterozygotes, and to correlate G2 arrest with other prognostic indicators of these cancers and in vivo radiosensitivity. Epstein-Barr virus-transformed lymphoblastoid cells were established from 108 female patients with breast cancer and 24 age-matched female control subjects, and from 45 patients with bladder cancer and 18 age-matched control subjects. Cells were exposed to 3 Gy of gamma radiation, and the percentages of cells in G1 and G2 phases were determined at 18 and 24 hours after irradiation by fluorescence-activated cell sorter analysis. Postirradiation delay in G2 phase was determined by calculating the percentage of cells in G2 and by using the ratio G2/G1. When we determined the percentage of cells in G2 phase at 18 hours after irradiation in 108 lymphoblastoid cells from breast cancer patients, we observed an increase of between 3% and 38% in the number of cells in G2 phase in comparison with cells that were not irradiated. Comparison with previous G2-phase arrest data for ataxia-telangiectasia heterozygotes using a cutoff point at 29% delay demonstrated that 20% and 8% of the breast cancer cell lines of the case patients and control subjects, respectively, fell into that category (P < .001). At the same time after irradiation, it was not possible to distinguish between bladder cancer cell lines (7%) and those of the corresponding control group (6%). Assessment of radiation effects by G2/G1 ratio showed that 18% of the breast cancer patients and 8% of the control subjects were in the high range. When G2 arrest was correlated with other prognostic factors, we found that case patients with a greater G2 block were more likely to have had a family history of breast cancer (P < .006) and more aggressive tumors when assessed by number of involved lymph nodes (P < .002) and tumor size (P < .05). Furthermore, an adverse response to radiotherapy was observed in a group of patients with high G2 arrest. While the postirradiation increase in G2-phase arrest in cells from breast cancer patients observed in this study may indicate genetic heterozygosity for ataxia-telangiectasia, it might also reflect other genetic abnormalities important to breast cancer.


Test-retest reliability of resting-state magnetoencephalography power in sensor and source space.
Several studies have reported changes in spontaneous brain rhythms that could be used as clinical biomarkers or in the evaluation of neuropsychological and drug treatments in longitudinal studies using magnetoencephalography (MEG). There is an increasing necessity to use these measures in early diagnosis and pathology progression; however, there is a lack of studies addressing how reliable they are. Here, we provide the first test-retest reliability estimate of MEG power in resting-state at sensor and source space. In this study, we recorded 3 sessions of resting-state MEG activity from 24 healthy subjects with an interval of a week between each session. Power values were estimated at sensor and source space with beamforming for classical frequency bands: delta (2-4 Hz), theta (4-8 Hz), alpha (8-13 Hz), low beta (13-20 Hz), high beta (20-30 Hz), and gamma (30-45 Hz). Then, test-retest reliability was evaluated using the intraclass correlation coefficient (ICC). We also evaluated the relation between source power and the within-subject variability. In general, ICC of theta, alpha, and low beta power was fairly high (ICC > 0.6) while in delta and gamma power was lower. In source space, fronto-posterior alpha, frontal beta, and medial temporal theta showed the most reliable profiles. Signal-to-noise ratio could be partially responsible for reliability as low signal intensity resulted in high within-subject variability, but also the inherent nature of some brain rhythms in resting-state might be driving these reliability patterns. In conclusion, our results described the reliability of MEG power estimates in each frequency band, which could be considered in disease characterization or clinical trials.


The associations of BMI trajectory and excessive weight gain with demographic and socio-economic factors: the Adolescent Nutritional Assessment Longitudinal Study cohort.
Assessing changes in adolescents' BMI over brief periods could contribute to detection of acute changes in weight status and prevention of overweight. The objective of this study was to analyse the BMI trajectory and the excessive weight gain of Brazilian adolescents over 3 years and the association with demographic and socio-economic factors. Data regarding the BMI of 1026 students aged between 13 and 19 years were analysed over 3 consecutive years (2010, 2011 and 2012) from the Adolescent Nutritional Assessment Longitudinal Study. Linear mixed effects models were used to assess the BMI trajectory according to the type of school attended (public or private), skin colour, socio-economic status and level of maternal schooling by sex. Associations between excessive weight gain and socio-economic variables were identified by calculation of OR. Boys attending private schools (β coefficient: 0·008; P=0·01), those with white skin (β coefficient: 0·007; P=0·04) and those whose mothers had >8 years of schooling (β coefficient: 0·009; P=0·02) experienced greater BMI increase than boys and girls in other groups. Boys in private schools also presented higher excessive weight gain compared with boys attending public schools (P=0·03). Boys attending private schools experienced greater BMI increase and excessive weight gain, indicating the need to develop specific policies for the prevention and reduction of overweight in this population.


Changes in amount and synthesis of poly(A)- and poly(A)+ RNA in growing and resting cultures of Tetrahymena.
This investigation deals both qualitatively and quantitatively with the changes of RNA content and synthesis during the culture growth cycle of Tetrahymena. Affinity chromatography with an oligo(dT) column was used to separate poly(A)+ RNA from total RNA. The rates of synthesis of poly(A)- and poly(A)+ RNA were determined in terms of the incorporation of [5-3H]uridine. During the log phase, the cellular RNA and protein contents decreased steadily, whereas during the resting stage, both were constant. The extents of decrease of both fractions of RNA were essentially the same (54.4% and 50.6% for total and poly(A)+ RNA, respectively). Therefore, the relative contents of poly(A)+ RNA was constant from the beginning of the log to the resting stage (4.58%). The decrease in protein content, however, amounted to only 24.8%. Theoretically, a change in the age distribution during culture growth would cause a lower content of both fractions of RNA. The extents of the decrease in the rate of synthesis of both fractions were the same (75% and 79% for poly(A)- and poly(A)+ RNA, respectively). However, this reduction is so large that it cannot be solely the result of a shift of the age distribution of the cell population.


Controversies in paraesophageal hernia repair: a review of literature.
The surgical repair of paraesophageal hiatal hernias (PHH) can be performed by endoscopic means, but the procedure is not standardized and results have not been evaluated systematically so far. The aim of this review article was to clarify controversial subjects on the surgical approach and technique, i.e., recurrence rate after conventional versus laparoscopic PHH treatment, results of mesh reinforcement of the cruroplasty, the necessity for additional antireflux surgery, and indications for an esophageal lengthening procedure. An electronic Medline search was performed to identify all publications reporting on laparoscopic and conventional PHH surgery. The computer search was followed by additional hand searches in books, journals, and related articles. All types of publications were evaluated because of a lack of high-level evidence studies such as randomized controlled trials. Critical analysis followed for all articles describing a study population of >10 patients and those reporting postoperative outcome. A total of 32 publications were reviewed. Randomized controlled trials comparing laparoscopic and open techniques could not be identified. Nineteen of the publications described the results of retrospective series. Therefore, most of the studies retrieved were low in hierarchy of evidence (level II-c or lower). The overall median hospital time as published was 3 days for patients operated laparoscopically and 10 days in the conventional group. Postoperative complications, such as pneumonia, thrombosis, hemorrhage, and urinary and wound tract infections, appeared to be more frequent after conventional surgery. Follow-up was longer for conventional surgery (median 45 months versus 17.5 months after the laparoscopic technique). Recurrence rates reported were higher in patients operated conventionally (median 9.1% versus 7.0% for patients operated laparoscopically). Recurrences after PHH repair may decrease with usage of mesh in the hiatus, although uniform criteria for this procedure are lacking. No conclusions could be drawn regarding the necessity for an additional antireflux procedure. Furthermore, uniform specific indications for the need of an esophageal lengthening procedure or preoperative assessment methods for shortened esophagus could not be detected. Treatment based on standardized protocols for preoperative assessment and postoperative follow-up is required to clarify the current controversies.


Case Presentation: A 63-year-old Man with Bilateral Adrenal Mass and Large Renal Cell Carcinoma.
The challenging case of an asymptomatic 63-yr-old man with a large renal cell carcinoma, bilateral adrenal mass, and small pancreatic and pulmonary nodules suspicious for metastases is presented. Treatment strategy is discussed by a surgeon recommending immediate cytoreductive nephrectomy and unilateral adrenalectomy as the first step and a medical oncologist favouring systemic targeted therapy at symptomatic disease progression.


Severe immune thrombocytopenia in two patients with systemic sclerosis.
Thrombocytopenia in the context of systemic sclerosis (SSc) is rare. It should primarily raise the possibility of scleroderma renal crisis. Immune thrombocytopenia (ITP) is another cause of low platelets that is common in systemic lupus erythematosus, but tremendously rare in patients with SSc. We herein report two cases of severe ITP in patients with SSc. The first case is a 29-year-old woman with very low platelet counts (2×109/L) that did not increase despite receiving corticosteroids, intravenous immunoglobulins (IVig), rituximab and romiplostim. Because of a symptomatic acute subdural haematoma, emergency splenectomy was performed and subsequently platelet counts normalised without neurological sequelae. The second case is a 66-year-old woman in whom self-limited mild epistaxis revealed low platelet counts (8×109/L). The patient did not improve after the use of IVig and corticosteroids. Secondarily rituximab and romiplostim normalised the platelet counts after 8 weeks. To the best of our knowledge this is the first reported case of severe ITP in a patient with diffuse cutaneous SSc and anti-topoisomerase antibodies.


Colorectal polyps and diet: a case-control study in Marseilles.
This study investigates the differences in usual past diet between 252 subjects with newly diagnosed adenomatous or villous polyps of the colon and rectum and a group of 238 hospital controls. Cases and controls were interviewed in hospital by 3 nutritionists using a dietary history questionnaire focused on the diet during the preceding year. Nutrient intake was estimated by means of ad hoc food tables adapted from French and British tables. Out of 16 food groups considered in the analyses, the cases reported lower consumption of oil and potatoes and higher consumption of sugar added to food and drink. Among nutrients, we found that cases had a lower consumption of carbohydrates (not taking into account added sugar), potassium, magnesium and vitamin B6. We found a slightly lower intake of fibre and a slightly higher intake of saturated fat among cases, though neither was statistically significant. Intake values for fibre and for carbohydrates were highly intercorrelated and, due to measurement errors, the effect of one may be masked by the other and vice versa. The hypothesis that some components of carbohydrates (starches, fibre and natural sugars but not added sugar) play a protective role in relation to the biology of tumours of the intestinal tract is considered in further multivariate analyses and in the "Discussion".