Diphtheria immunity of Albanian and other eastern European immigrants in Greece compared with the local population--the risk of reemergence in Greece.
A large number of immigrants have come to Greece from diphtheria-endemic countries during the past 8 years. Information on the immune status against diphtheria among immigrants from Albania and the New Independent States (NIS) of the former USSR, as well as the Greek population, is essential in planning public health control measures. The main objective of the study was to determine the risk of the spread of diphtheria if new cases arrived in the country. Diphtheria antitoxin (DAT) in sera from 185 healthy individuals from northern Greece and 227 immigrants from Albania and the NIS was titrated using a quantitative ELISA test. The participants were adults aged 22 to 46 years. Titers were considered as protective when DAT levels were higher or equal to 0.1 IU/ml. Albanian immigrants exhibited the highest rates of protective titers (99 of 167, 59.3%), while lower immunity rates were detected among immigrants from the NIS (20 of 60, 33.3%) (1.5 < OR = 2.9 < 5.4, p = 0.0007) as well as among Greek participants (47 of 185, 25.4%) (2.8 < OR = 4.4 < 7.0, p = 0.00001). Immunity rates did not differ between Greek and NIS participants. DAT levels of persons with protective titers differed between the three population groups (analysis of variance, p = 0.0005), with the highest mean DAT values detected among NIS immigrants (0.613 IU/ml). Lower values were found among protected Albanians (0.482 IU/ml) and Greeks (0.314 IU/ml). There was no significant age- and sex-related difference in immunity rates and DAT levels among the groups. The low immunity rates among Greek adults might suggest that they have had no natural contact with toxigenic strains of corynebacteria. A booster dose of diphtheria toxoid for local adults is recommended, to reduce their risk of acquiring toxigenic strains from individuals who may carry the bacteria without exhibiting clinical disease.


A single cell density-sensing factor stimulates distinct signal transduction pathways through two different receptors.
In Dictyostelium discoideum, cell density is monitored by levels of a secreted protein, conditioned medium factor (CMF). CMFR1 is a putative CMF receptor necessary for CMF-induced G protein-independent accumulation of the SP70 prespore protein but not for CMF-induced G protein-dependent inositol 1,4,5-trisphosphate production. Using recombinant fragments of CMF, we find that stimulation of the inositol 1,4,5-trisphosphate pathway requires amino acids 170-180, whereas SP70 accumulation does not, corroborating a two-receptor model. Cells lacking CMFR1 do not aggregate, due to the lack of expression of several important early developmentally regulated genes, including gp80. Although many aspects of early developmental cAMP-stimulated signal transduction are mediated by CMF, CMFR1 is not essential for cAMP-stimulated cAMP and cGMP production or Ca(2+) uptake, suggesting the involvement of a second CMF receptor. Exogenous application of antibodies against either the region between a first and second or a second and third possible transmembrane domain of CMFR1 induces SP70 accumulation. Antibody- and CMF-induced gene expression can be inhibited by recombinant CMFR1 corresponding to the region between the first and third potential transmembrane domains, indicating that this region is extracellular and probably contains the CMF binding site. These observations support a model where a one- or two-transmembrane CMFR1 regulates gene expression and a G protein-coupled CMF receptor mediates cAR1 signal transduction.


Velocity distribution function of sputtered Cu atoms obtained by time resolved optical absorption spectroscopy.
A new method based on time resolved optical absorption spectroscopy is proposed to determine the velocity distribution function of sputtered Cu atoms in a magnetron plasma discharge. The method consists of applying a short pulse of 1.5 micros and of recording time variations in copper atom density in off pulse at different positions (1, 2, and 3 cm) from target surface under 3-30 mTorr. The time evolution of the density is then converted into velocity distribution. We estimate that only sputtered atoms with radial velocity component lower than 0.5 km/s are detected. The average velocity of Cu atoms is evaluated as the first order moment of the velocity distribution functions. The velocity distribution functions become the more dispersive the farther from target surface. The average velocities vary in the range of 2.5-3 km/s at the vicinity of target surface whereas at 3 cm a decrease from 2.5 to 1.2 km/s is observed at 30 mTorr.


An improved method for using electrolyte leakage to assess membrane competence in plant tissues.
A new expression for ion leakage from plant tissue, the tissue ionic conductance (g(Ti)), is compared with electrical conductivity (EC) and a commonly used damage index (I(d)) to test the ability of each expression to correctly describe leakiness in two model systems representing examples of physiological processes with well-known effects on membrane permeability. In experiments in which drought-acclimated leaves were compared with nonacclimated leaves and senescing leaves were compared with nonsenescing leaves, I(d) contradicted our expectation that acclimated tissue would be less leaky than nonacclimated tissue, and g(Ti) and EC confirmed this expectation. In a comparison of senescing and nonsenescing tissue, I(d) again contradicted our expectation that senescing tissue would be more leaky than nonsenescing, and EC and g(Ti) were confirming. Using a diffusion analysis approach, we show that I(d) fails to account for variation in the concentration gradient between the tissue and the bathing solution and variation in the surface area through which efflux occurs. Furthermore, because I(d) is a parameter that relates treatment performance to control performance as a percentage value, it distorts the actual differences among treatments. The resulting artifacts lead to a presentation of membrane integrity which is probably incorrect. EC is a more direct measurement of net ion efflux and appears to be less vulnerable to artifact. However, because g(Ti) is the only expression that explicitly includes chemical driving force and tissue surface area, it is the most reliable of the three expressions.


Study on the Correlation Between Ischemic Leukoaraiosis and Cerebral Large Artery Stenosis Using the Stages of the Preinfarction Period Based on the Result of Computed Tomography Perfusion.
The influence of cerebral large artery stenosis (CLAS) on ischemic leukoaraiosis (LA) remains elusive. Based on the proposed stages of the preinfarction period, this study aimed to adopt the staging system to assess the correlation between ischemic LA and CLAS. Patients with unilateral CLAS ≥50% and without cerebral stroke were screened. The severity and distribution of stenosis were evaluated on computed tomography angiography images. The degree of regional cerebral perfusion was rated according to the stages of preinfarction period: 0=normal, 1=stage Ia, 2=stage Ib, 3=stage IIa, 4=stage IIb. Stage I included stage Ia and stage Ib. Stage II included stage IIa and stage IIb. LA was scored with Fazakas scale on T2-weighted image and/or fluid-attenuated inversion recovery sequences. The cohort consisted of 212 patients (mean age, 66.89±11.39 y), including 145 (68.40%) males. CLAS severity and distribution did not differ between patients with and without LA (P>0.05). Normal, stage I, and stage II had significantly different incidences of LA and hemispheric LA scores in the left and right hemispheres (P<0.05). The degree of regional cerebral perfusion was independently associated with LA in the left (P=0.0094) and right hemispheres (P=0.0091). Ischemic LA is not directly related to CLAS but is independently associated with the degree of CLAS-induced cerebral hypoperfusion. The stages of the preinfarction period are helpful in identifying people at high risk of LA progression.


Enhanced Detection of Genitourinary Cancers Using Fragmentation and Copy Number Profiles Obtained from Urinary Cell-Free DNA.
Recent studies have reported that examining the fragmentation profiles (FP) of plasma cell-free DNA (cfDNA) further improves the clinical sensitivity of tumor detection. We hypothesized that considering the differences of the FP of urinary cfDNA would increase the clinical sensitivity of genitourinary (GU) cancer detection. 177 patients with GU cancer and 94 individuals without tumors were enrolled in the discovery cohort. An independent validation dataset comprising 30 patients without tumors and 66 patients with GU cancer was also collected. We constructed an ensemble classifier, GUIDER, to detect and localize GU cancers using fragmentation and copy number profiles obtained from shallow whole-genome sequencing of urinary cfDNA. Urinary cfDNA of patients with GU cancer had a higher proportion of long fragments (209-280 bp) and a lower proportion of short fragments (140-208 bp) compared to controls. The overall mean classification accuracy of the FP was 74.62%-85.39% for different algorithms, and integration of the FP and copy number alteration (CNA) features further enhanced the classification of samples from patients with GU cancer. The mean diagnostic accuracy was further improved by the ensemble classifier GUIDER, which integrated the FP and CNA profiles and resulted in a higher mean accuracy (87.52%) compared to the analysis performed without FP features (74.62%). GUIDER performed well in an independent validation dataset. The lengthening and shortening of urinary cfDNA within specific size ranges were identified in patients with GU cancer. Integration of the FP should further enhance the ability to use urinary cfDNA as a molecular diagnostic tool.


Optomechanical atomic force microscope.
In the scanning probe microscope system, the weak signal detection of cantilever vibration is one of the important factors affecting the sensor sensitivity. In our current work, we present a novel design concept for an atomic force microscope (AFM) combined with optomechanics with an ultra-high quality factor and a low thermal noise. The detection system consists of a fixed mirror placed on the cantilever of the AFM and pump-probe beams that is equivalent to a Fabry-Perot cavity. We realize that the AFM combined with an optical cavity can achieve ultra-sensitive detection of force gradients of 10-12 N m-1 in the case of high-vacuum and low effective temperature of 1 mK, which may open up new avenues for super-high resolution imaging and super-high precision force spectroscopy.


Does the liquid method of electret forming influence the adhesion of blood platelets?
This work presents the results of the effect of the electric charge on the adhesion of blood platelets. All experiments were carried out on polyethylene foil. The liquid method was used to form electrets. The evaluation of the electret effect influence on the adhesion of blood platelets was made on the basis of the observation of the electret surface after the contact with fresh citrate human blood group O Rh+ in an electron scanning microscope. Experimental results confirmed the essential influence of the electric charge on the process of adhesion of blood platelets. It was noticed that the preliminary aging of electrets decreases the density of the surface charge and improves the athrombogenic characteristics of polyethylene foil.


Collagen Organization Critical Role in Wound Contraction.
Open wound closure by wound contraction produces a healed defect made up mostly of dermis. Generating thicker collagen fibers condenses granulation tissue, which pulls surrounding skin into the defect. What is the mechanism for open wound contraction? Is it through the generation of contractile force using sustained myosin ATPase, thus causing cell contraction or by rapid myosin ATPase that condenses collagen fibrils into fibers? The mechanism for wound contraction is not often debated after the discovery of the myofibroblast. Myofibroblasts are the major cell phenotype in maturing granulation tissue. It is concluded, not quite accurately, that myofibroblasts are responsible for wound contraction. As wound contraction progresses, polarized light microscopy reveals birefringence patterns associated with ever-increasing thickening of collagen fibers. Collagen fibers thicken by eliminating water between fibrils. Wound contraction requires collagen synthesis and granulation tissue compaction. Both myofibroblasts and fibroblasts synthesize collagen, but fibroblasts, not myofibroblasts, compact collagen. Free-floating fibroblast-populated collagen lattices (FPCL) contract by rapid myosin ATPase, thus resulting in thicker collagen fibers by elongated fibroblasts. The release of an attached FPCL, using sustained myosin ATPase, produces rapid lattice contraction, now populated with contracted myofibroblasts in the absence of thick collagen fibers. In vivo and in vitro studies show that rapid myosin ATPase is the motor for wound contraction. Myofibroblasts maintain steady mechano-tension through sustained myosin ATPase, which generates cell contraction forces that fail to produce thicker collagen fibers. The hypothesis is that cytoplasmic microfilaments pull collagen fibrils over the fibroblast's plasma membrane surface, bringing collagen fibrils in closer contact with one another. The self-assembly nature of collagen fixes collagen fibrils in regular arrays generating thicker collagen fibers. Wound contraction progresses through fibroblasts generating thicker collagen fibers, using tractional forces; rather than by myofibroblasts utilizing cell contraction forces.


A DNA Vaccine Encoding Plasmodium falciparum PfRH5 in Cationic Liposomes for Dermal Tattooing Immunization.
Vaccines are the primary means of controlling and preventing pandemics and outbreaks of pathogens such as bacteria, viruses, and parasites. However, a major drawback of naked DNA-based vaccines is their low immunogenicity and the amount of plasmid DNA necessary to elicit a response. Nano-sized liposomes can overcome this limitation, enhancing both nucleic acid stability and targeting to cells after administration. We tested two different DNA vaccines in cationic liposomes to improve the immunogenic properties. For this, we cloned the coding sequences of the Plasmodium falciparum reticulocyte binding protein homologue 5 (PfRH5) either alone or fused with small the small hepatitis virus (HBV) envelope antigen (HBsAg) encoding sequences, potentially resulting in HBsAg particles displaying PfRH5 on their outside. Instead of invasive intraperitoneal or intramuscular immunization, we employed intradermal immunization by tattooing nano-encapsulated DNA. Mice were immunized with 10 μg encapsulated DNA encoding PfRH5 alone or in fusion with HBsAg and this elicited antibodies against schizont extracts (titer of 104). Importantly, only IgG from animals immunized with PfRH5-HBs demonstrated sustained IgG-mediated inhibition in in vitro growth assays showing 58% and 39% blocking activity after 24 and 48 h, respectively. Intradermal tattoo-vaccination of encapsulated PfRH5-HBsAg coding plasmid DNA is effective and superior compared with an unfused PfRH5-DNA vaccine, suggesting that the HBsAg fusion may be advantageous with other vaccine antigens.


A rare cause of acute abdominal disease: two reports of caecal diverticulum perforation.
Diverticulum of the caecum is a rare lesion. From a clinical point of view, the inflammation it causes can mimic symptoms of acute appendicitis, causing difficulties in diagnosis and thus prescription of appropriate treatment. It is almost impossible to differentiate this disease from acute appendicitis through physical examination alone, and radiological imaging may also prove insufficient. For this reason, it is common to perioperatively diagnose diverticula of the caecum. Two cases of patients who underwent surgery for perforated caecal diverticula are presently described.


Influence of flocculation and settling properties of activated sludge in relation to secondary settler performance.
Floc characteristics were studied at a full scale activated sludge treatment plant with a unique process solution incorporating pre-denitrification with post-nitrification in nitrifying trickling filters. Since greater nitrogen removal is achieved when more secondary settled wastewater is recirculated to the trickling filters, the secondary settlers are always operated close to their maximal capacity. The flocculation and settling properties are therefore crucial and have an effect on the overall plant performance. Since the plant is operated at a short sludge age, these properties change quickly, resulting in variable maximal secondary settler capacity. The dynamics in floc structure and microbial community composition were studied and correlated to the secondary settler performance. Fluorescence in situ hybridisation was used to investigate the microbial community structure and their spatial distribution. The floc structure could to some extent be related to the flocculation and settling properties of the sludge. Even small differences had an influence suggesting that colloidal properties also play a significant role in determining the floc properties. No correlation between microbial community composition and settling properties could be established with the group-specific probes investigated.


Establishment of a promoter-based chromatin architecture on recently replicated DNA can accommodate variable inter-nucleosome spacing.
Nucleosomes, the fundamental subunits of eukaryotic chromatin, are organized with respect to transcriptional start sites. A major challenge to the persistence of this organization is the disassembly of nucleosomes during DNA replication. Here, we use complimentary approaches to map the locations of nucleosomes on recently replicated DNA. We find that nucleosomes are substantially realigned with promoters during the minutes following DNA replication. As a result, the nucleosomal landscape is largely re-established before newly replicated chromosomes are partitioned into daughter cells and can serve as a platform for the re-establishment of gene expression programmes. When the supply of histones is disrupted through mutation of the chaperone Caf1, a promoter-based architecture is generated, but with increased inter-nucleosomal spacing. This indicates that the chromatin remodelling enzymes responsible for spacing nucleosomes are capable of organizing nucleosomes with a range of different linker DNA lengths.


Polo-like kinase 2 promotes chemoresistance and predicts limited survival benefit from adjuvant chemotherapy in colorectal cancer.
Colorectal cancer (CRC) is one of the most common malignances worldwide. Chemoresistance remains a major issue in the field of CRC treatment. The present study aimed to investigate the potential role of polo-like kinase 2 (Plk2) in chemoresistance in CRC. The associations between Plk2 and clinicopathological factors, as well as chemotherapeutic benefit were analyzed with a publicly available CRC dataset. The correlation between Plk2 expression and chemosensitivity was further confirmed in CRC cells. Moreover, knockdown and exogenous overexpression experiments of Plk2 were carried out to uncover the potential role of Plk2 in regulating the chemoresistance of CRC cells. We found that the expression of Plk2 was significantly associated with proximally located tumors. In addition, it was found that high expression ofPlk2 was associated with deficient mismatch repair status, B‑raf serine/threonine kinase proto‑oncogeneand Kirsten rat sarcoma viral oncogene homolog mutations. By contrast, tumor protein 53 mutation was correlated with a low expression level of Plk2. A higher expression level of Plk2 significantly predicted a poorer outcome in patients with CRC. However, the prognostic significance was only observed in patients who received adjuvant chemotherapy. In CRC cells, higher levels of Plk2 were associated with increased resistance to chemotherapeutic agents. Knocking down the expression of Plk2 resulted in elevated cellular apoptosis induced by oxaliplatin. By contrast, exogenous overexpression of Plk2 exerted an anti-apoptotic effect and enhanced the resistance of CRC cells to chemotherapeutic agents. In conclusion, a high expression of Plk2 was associated with chemoresistant traits of CRC through inhibiting apoptosis. These results suggested that Plk2 may serve as a predictive marker for chemoresistance and a novel target in CRC treatment.


Hematologic changes predict clinical outcome in recovered patients with COVID-19.
2019 coronavirus disease (COVID-19) presents as a newly recognized pneumonia that has brought about a global pandemic and is increasingly considered as a systemic illness. We investigated the clinical and laboratory features of recovered COVID-19 patients without pre-existing hematologic diseases at Wuhan No. 1 Hospital. Fifty-nine male and 68 female Chinese patients were included with the median age at 64 years in the present study. Eosinopenia (37.80%), monocytosis (51.97%), lymphocytopenia (25.20%), and anemia (51.97%) were the most common hematologic findings in our cohort, particularly in severe or critically ill COVID-19. The levels of changes in leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, platelets, hemoglobin levels, mean corpuscular volume (MCV), and mean cell hemoglobin concentration (MCHC) are overall associated with lung involvement, oxygen demand, and disease activity. However, changes of eosinophils (end hospitalization-baseline) (coefficients = 10.32; 95% CI = 1.03-19.60, P = 0.03) and basophils (Max - Min) (coefficients = 71.43; 95% CI = 8.55-134.31, P = 0.03) were independent predictors of delayed recovery in the hospital by the multivariate analysis in this recovered population. A variety of hematologic changes are associated with the severity and clinical outcome of recovered COVID-19 patients, which warrants further exploration of their underlying mechanisms.


Surgery for thoracic empyema: personal experience and current highlights.
Thoracic empyema remains challenging for thoracic surgeons. The principles of empyema treatment are early diagnosis and early treatment. Decision-making involves a triad consisting of the etiology of empyema, general condition of the patient and stage of disease. For acute empyema, early surgical intervention, such as video-assisted thoracoscopic debridement, is recommended when conventional chest tube drainage has failed. Radical treatments of chronic empyema include 1 removal of the empyema space (decortication with or without lung resection) and 2 obliteration of the pleural space with muscle flaps or omentum flaps, or by thoracoplasty. Decortication is the procedure of choice for patients with re-expandable underlying lung. For patients who are not eligible for the above-mentioned radical treatment, open-window thoracostomy can be considered. The current attitudes show that the present concepts are based mainly on expert opinion. No exclusive sequence of procedures leading to a uniformly predictable successful outcome is available. Individualized approaches can be recommended based on institutional practice and local protocols.


Genetic diversity and worldwide distribution of the deltavirus genus: A study of 2,152 clinical strains.
Hepatitis delta virus (HDV) is responsible for the most severe form of acute and chronic viral hepatitis. We previously proposed that the Deltavirus genus is composed of eight major clades. However, few sequences were available to confirm this classification. Moreover, little is known about the structural and functional consequences of HDV variability. One practical consequence is the failure of most quantification assays to properly detect or quantify plasmatic HDV RNA. Between 2001 and 2014, 2,152 HDV strains were prospectively collected and genotyped in our reference laboratory by means of nucleotide sequencing and extensive phylogenetic analyses of a 400-nucleotide region of the genome (R0) from nucleotides 889 to 1289 encompassing the 3' end of the delta protein-coding gene. In addition, the full-length genome sequence was generated for 116 strains selected from the different clusters, allowing for in-depth characterization of the HDV genotypes and subgenotypes. This study confirms that the HDV genus is composed of eight genotypes (HDV-1 to HDV-8) defined by an intergenotype similarity >85% or >80%, according to the partial or full-length genome sequence, respectively. Furthermore, genotypes can be segregated into two to four subgenotypes, characterized by an intersubgenotype similarity >90% (>84% for HDV-1) over the whole genome sequence. Systematic analysis of genome and protein sequences revealed highly conserved functional nucleotide and amino acid motifs and positions across all (sub)genotypes, indicating strong conservatory constraints on the structure and function of the genome and the protein. This study provides insight into the genetic diversity of HDV and a clear view of its geographical localization and allows speculation as to the worldwide spread of the virus, very likely from an initial African origin. (Hepatology 2017;66:1826-1841).


Award for Distinguished Scientific Early Career Contributions to Psychology: Dobromir Rahnev.
The Early Career Awards, given for the first time in 1974, recognize the large number of excellent early career psychologists. Recipients of this award may not have held a doctoral degree for more than nine years. For purposes of this award, psychology has been divided into 10 areas: animal learning and behavior, comparative; developmental; health; cognition/human learning; psychopathology; behavioral and cognitive neuroscience; perception/motor performance; social; applied research; and individual differences. Five areas are considered each year, with areas rotated in two-year cycles. The areas considered in 2021 were animal learning and behavior, comparative; developmental; health; cognition/human learning; and psychopathology. Each year, panels are selected for the areas under consideration, and these panels recommend nominees to the Committee on Scientific Awards. The 2021 recipients of the APA Scientific Contribution Awards were recognized by the 2020 Board of Scientific Affairs and selected by the 2020 Committee on Scientific Awards. For outstanding contributions to the fields of perceptual decision making and visual metacognition. Dobromir Rahnev's work has revealed the determinants of subjective evaluation in perceptual tasks, the sources of metacognitive inefficiency, and the neural implementation of the control of perceptual decision making in the prefrontal cortex. Rahnev's research on the suboptimality of perception is beginning to shift the role of optimality in the field. He creatively combines computational modeling, functional neuroimaging, brain stimulation, and psychophysics, while his dedication to the principles of open science has resulted in the creation of large repositories of open data such as the Confidence Database. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Environmental psychology 1989-1994.
A review of research and theory on transactions between people and physical environments emphasizes new contributions to theory and empirical research published in major journals of environmental psychology, 1989-1994. Theories focused on arousal, load, stress, privacy-regulation, behavior settings, and transactional analysis; new theory increasingly incorporated situational and contextual variables. Empirical research emphasized field settings over the laboratory and employed increasingly diverse methods, populations, and cultures. Environmental design studies integrated scientific and applied goals through post-occupancy evaluation. New findings concerned features of residences, work places, hospitals, schools, prisons, and larger community environments. New studies also addressed environmental stressors (e.g., temperature, noise); effects of attitudes and behaviors on conservation, crime, pollution, and hazards; and issues for neighborhoods, public places, and natural environments. Directions for the future include integrated theory to guide research, more design experiments, and development of conventions for case studies.


Hydrocode Investigations of Terminal Astroballistics Problems during the Hypothetical Future Planetary Defense System's Space Mission.
The article is devoted to the preliminary concept of the Future Planetary Defense System (FPDS) emphasizing astroballistics. This paper is intended to support international efforts to improve the planetary security of Earth. The work covers three areas of knowledge: astronautics, astrodynamics, and astroballistics. The most important part of the presented article is dynamic, contact combat modeling against small, deformable celestial bodies. For these purposes, the original, proprietary hydrocode of the free particle method (HEFPM-G) with gravity was used. The main aim of combat is to redirect potentially hazardous objects (PHOs) to orbits safe for Earth or destroy them. This concept's first task is to find, prepare, and use dynamic three-dimensional models of the motion of celestial bodies and spacecraft or human-crewed spaceships in the solar system's relativistic frame. The second task is to prepare the FPDS' architecture and computer simulation space missions' initial concepts in the internal part of the solar system. The third and main task covers simulating, using hydrocodes, and selected methods of fighting 100 m diameter rock material asteroids.


Distress and psychosocial risk in families with newly diagnosed pediatric brain tumors.
In BriefThe investigators administered surveys to parents whose children were hospitalized with a brain tumor. They learned that parents in this situation are highly distressed, and that families have multiple sources of stress when a child is hospitalized. The investigators used this information to improve the psychosocial supportive care provided at their hospital. In general, these findings have the potential to improve the patient's and family's experience with a new brain tumor by guiding teams to address family needs as well as the child's acute medical needs.


Susceptibility of corneas from various animal species to in vitro binding and invasion by Acanthamoeba castellanii [corrected].
A crucial requirement for establishing corneal infection by the extracellular protozoal parasite, Acanthamoeba, is the ability of the parasite to bind to the corneal surface. In a series of in vitro studies, we examined the ability of Acanthamoeba castellanii [corrected] to adhere, invade, and damage normal, intact corneas of 11 mammalian and one avian species. A. castellanii [corrected] (80-90% trophozoites and 10-20% cysts) were incubated with corneas for 24 hours in vitro and examined by scanning electron microscopy (SEM). Results of several independent SEM experiments revealed that parasites not only failed to produce cytopathic effects but did not even bind to the corneal epithelium of mice, rats, cotton rats, horses, guinea pigs, cows, chickens, dogs, and rabbits. However, parasites adhered, invaded, and produced severe damage to human, pig, and Chinese hamster corneas during the 24-hour in vitro incubation period. Additional in vitro experiments quantified the binding of A. castellanii [corrected] to the corneas of selected susceptible and nonsusceptible species. In vitro binding assays revealed scant binding of parasites to mouse, rat, and rabbit (range = 5-20 parasites/7.07 mm2 corneal button). In contrast, extensive binding was observed on Chinese hamster, pig, and human corneas (range = 100-200 parasites/7.07 mm2 button). The results indicate that A. castellanii [corrected] exercises rigid host specificity at the host cell surface.


Carbon gain and photosynthetic response of chrysanthemum to photosynthetic photon flux density cycles.
Most models of carbon gain as a function of photosynthetic irradiance assume an instantaneous response to increases and decreases in irradiance. High- and low-light-grown plants differ, however, in the time required to adjust to increases and decreases in irradiance. In this study the response to a series of increases and decreases in irradiance was observed in Chrysanthemum x morifolium Ramat. "Fiesta" and compared with calculated values assuming an instantaneous response. There were significant differences between high- and low-light-grown plants in their photosynthetic response to four sequential photosynthetic photon flux density (PPFD) cycles consisting of 5-minute exposures to 200 and 400 micromoles per square meter per second (mumol m(-2)s(-1)). The CO(2) assimilation rate of high-light-grown plants at the cycle peak increased throughout the PPFD sequence, but the rate of increase was similar to the increase in CO(2) assimilation rate observed under continuous high-light conditions. Low-light leaves showed more variability in their response to light cycles with no significant increase in CO(2) assimilation rate at the cycle peak during sequential cycles. Carbon gain and deviations from actual values (percentage carbon gain over- or underestimation) based on assumptions of instantaneous response were compared under continuous and cyclic light conditions. The percentage carbon gain overestimation depended on the PPFD step size and growth light level of the leaf. When leaves were exposed to a large PPFD increase, the carbon gain was overestimated by 16 to 26%. The photosynthetic response to 100 mumol m(-2) s(-1) PPFD increases and decreases was rapid, and the small overestimation of the predicted carbon gain, observed during photosynthetic induction, was almost entirely negated by the carbon gain underestimation observed after a decrease. If the PPFD cycle was 200 or 400 mumol m(-2) s(-1), high- and low-light leaves showed a carbon gain overestimation of 25% that was not negated by the underestimation observed after a light decrease. When leaves were exposed to sequential PPFD cycles (200-400 mumol m(-2) s(-1)), carbon gain did not differ from leaves exposed to a single PPFD cycle of identical irradiance integral that had the same step size (200-400-200 mumol m(-2) s(-1)) or mean irradiance (200-300-200 mumol m(-2) s(-1)).


Cell size-proliferation relationship in rat glioma cells.
The homeostasis of the central nervous system is highly controlled by glial cells and is dramatically altered in the case of glioma. In this respect, the complex connection between cell size and division is of particular importance and needs clarifying. In order to investigate this connection, cell number and volume were measured in C6 rat glioma cells under different experimental conditions, including continuous cell culture, Cl- channel blockade, and anisotonicity, and in the presence of an inhibitory conditioned medium collected from cell cultures or in a medium containing a low level of fetal calf serum. The rate of cell proliferation changed with cell volume in a bell-shaped manner, so that it is optimal within a cell volume window and appears to be controlled by low and high cell size checkpoints. The cell size-proliferation relationship can be defined by Boltzmann-like equations, which may reflect the effects of macromolecular crowding on proteins controlling the cell cycle progression. Altogether, these observations indicate that glioma cell proliferation is controlled predominantly but not exclusively by cell size-dependent mechanisms.


[Traumatic luxation of the extensor apparatus of the dorsum of the metacarpophalangeal joint of the little finger. Six cases].
Dislocation of the extensor tendon over the MP joint as a result of trauma is a rare and unrecognized injury as our six patients were only operated subsequently. The diagnosis is simple: flexion is possible, while extension is not. The patient is able to hold the extension despie resistance if the dislocation is reduced by artificial extension. X-rays eliminate any possible fracture. Six cases have revealed two different assumptions: either the two tendons (extensor digitorum communis and extensor digiti quinti proprius) are simultaneously dislocated together on the ulnar side, or they are dislocated on either sides of the joint. In the first assumption, the injury occurred ulnar-wise tearing the sagittal band. This case concerns the three older patients. The dislocation was reduced and stabilized by the Michon surgery method. The second assumption concerns the three youngest patients who suffered from a direct axial shock. This separation was reduced by suture of the two tendons on the dorsal base of the joint. The postoperative care was ensured in all cases by a splint attached to the palm, keeping the MP joint in extension and enabling immediate web-fingered reeducation. This therapeutic technique has given satisfactory results as over an average period of six years no recurrence of stiffness has been observed.


Correlates of sports practice, occupational and leisure-time physical activity in Brazilian adolescents.
To analyze the relationship between different physical activity (PA) domains and sociodemographic, psychological, behavioral and biological factors in Brazilian adolescents. 1,220 adolescents (55.1% female) aged between 10 and 16 years-old participated in this study. The Baecke questionnaire was used to evaluate different PA domains, namely occupational, sports and leisure-time. Socioeconomic status, number of siblings, friendships satisfaction, mother's and father's PA level and previous experience with sports were self-reported. Cardiorespiratory fitness, waist circumference, and somatic maturity were estimated by objective indicators. Linear regression was used for the main statistical analysis. The variables consistently related to all of the PA domains were gender (boys more active), friendship satisfaction (positive with sports and leisure-time PA and negative with occupational PA) and cardiorespiratory fitness (positive). There were also domain-specific relationships for occupational (number of siblings [β = 0.02] and father's PA [β = 0.13]), sport practice (previous experience with sports [β = 0.33], waist circumference [β = 0.01] and somatic maturity [β = -0.12]) and leisure-time PA (chronological age [β = -0.15], mother's PA [β = 0.47] and previous experience with sports [β = 0.17]). The different domains of PA are related to specific variables in adolescence. This information may be helpful in formulating strategies for physical activity promotion, particularly in adolescents from low-to-middle income countries.


Production of secretory component and pathogenesis of gastric cancer in Helicobacter pylori-infected stomach.
The purpose of this study was to examine the production of secretory component (SC) and immunoglobulin A (IgA) in the gastric mucosa with Helicobacter pylori infection and to investigate the influence of immunological reactions on various phases of infection (gastritis, intestinal metaplasia, gastric cancer). Production of SC and IgA was assessed by immunohistochemical staining in (1) endoscopic biopsy samples of H. pylori-eradicated cases (n = 25), and (2) surgically resected stomach tissues of H. pylori-positive gastric cancer cases, intestinal type (IGC, n = 25) and diffuse type (DGC, n = 25). Before eradication therapy, all samples showed positive staining of SC and IgA in epithelial cells, and IgA was also positive in plasma cells in the mucosal layer. H. pylori bacteria were positively stained for SC and IgA. After treatment, the degree of SC and IgA staining in epithelial cells was reduced with successful eradication; but with intestinal metaplasia, SC staining was positive regardless of the results of treatment. In nonmetaplastic mucosa, SC-positive cells were increased in the glandular neck zone to the surface mucosal layer; and the intensity of SC staining was increased in proportion to the degree of mucosal inflammation and IgA-positive cell aggregation. In intestinal metaplasia, SC was positive irrespective of the degree of inflammation. Most cancer foci also showed positive staining of SC, irrespective of histological type. Production of SC and IgA was thought to be a specific reaction against H. pylori infection, occurring from the early to the late stages and not limited to intestinal metaplasia. It was suggested that immunological reactions against H. pylori infection might generally be involved with the pathogenesis of intestinal metaplasia and both histological types of gastric cancer (IGC and DGC).


Identification of mutations conferring insecticide-insensitive AChE in the cotton-melon aphid, Aphis gossypii Glover.
We have identified two mutations in the ace1 gene of Aphis gossypii that are associated with insensitivity of acetylcholinesterase (AChE) to carbamate and organophosphate insecticides. The first of these, S431F (equivalent to F331 in Torpedo californica), is associated with insensitivity to the carbamate insecticide pirimicarb in a range of A. gossypii clones. The S431F mutation is also found in the peach-potato aphid, Myzus persicae (Sulzer), and a rapid RFLP diagnostic allows the identification of individuals of both aphid species with a resistant genotype. This diagnostic further revealed the presence of S431 in several other pirimicarb-susceptible aphid species. The serine at this position in the wild-type enzyme has only been reported for aphids and provides a molecular explanation of why pirimicarb has a specific aphicidal action. A less specific insensitivity to a wide range of carbamates and organophosphates is associated with a second mutation, A302S (A201 in T. californica).


[Epidemiology and prognosis of atrial fibrillation in Japanese population].
Atrial fibrillation (AF) is one of the common arrhythmias encountered in general practice as well as in the field of cardiology. AF could be responsible for increased mortality and various morbidities including clinical symptoms, impaired cardiac function and thromboembolism. An epidemiological study showed that prevalence of AF increased with the aging of the population and that the increase became striking after 60 years of age, affecting approximately 4 % in men and 2 % in women aged 80 years or more. Rhythm control with antiarrhythmic drugs and/or catheter ablation could not fully prevent AF reccurence. Understanding the epidemiology, risk factors, clinical course and prognosis of AF is very important to management of AF.


Goitre causing acute respiratory arrest.
A patient reported symptoms of upper airway obstruction for 4 years. His symptoms worsened with a viral upper respiratory infection and he suffered acute respiratory arrest. He was resuscitated and a large goitre with intrathoracic extension which was compressing the trachea was resected. The mechanisms of upper airway compromise by goitre are discussed. The symptoms of the effect of goitre on the airway are reviewed.


Systematic review of Spanish outcome measures on motor imagery ability: use in physical rehabilitation.
Motor imagery is a mental representation of movement without any body movement and its training accelerates motor learning and improves motor skills. A thorough understanding of how to manipulate mental images is necessary before using motor imagery in physical rehabilitation. This systematic review analyzes the psychometric properties of the outcome measures on motor imagery ability for the Spanish-speaking people and discusses its usefulness in people with motor disabilities. A review was conducted, using the COSMIN checklist to appraise 19 articles on measurement properties of motor imagery ability assessments found in reviewed databases. The criteria for grading the usefulness of instruments to measure motor imagery was established depending on the sensory modality assessed. We found 17 questionnaires. Methodological quality was mostly fair in reliability and validity. Four tests have been considered highly useful in assessing motor imagery. MIQ (alpha = 0.90; EFA=2) and MIQ-R (alpha = 0.84; EFA=2) are the best suited to evaluate motor imagery in Spanish-speaking population. To handle spatial images, MASMI (alpha = 0.93) or MARMI (alpha = 0.90) tests may be more beneficial. MIQ and MIQ-R evaluate visual and kinesthetic imagery, but these are difficult to use in the physical rehabilitation of people with motor disabilities. Currently, there are no valid Spanish translations of studies regarding motor imagery outcome measures for people with disabilities.


Testicular dysgenesis does not affect expression of anti-müllerian hormone by Sertoli cells in premeiotic seminiferous tubules.
Anti-Müllerian hormone (AMH) immunoreactivity was studied on paraffin sections obtained from archival testicular biopsies of 29 children with intersex disorders and of 22 controls. Strong AMH immunoreactivity was observed in Sertoli cell cytoplasm from 8 fetal weeks until puberty. During pubertal maturation, in both normal and intersex patients, AMH expression was present in premeiotic seminiferous tubules, but was no longer detected in neighboring tubules with meiotic development. AMH immunostaining was abolished in the testis of one patient with persistent Müllerian ducts due to a mutation of the AMH gene, but was conserved in the testes of two patients with mutations of the AMH receptor gene. Testicular dysgenesis usually results in sexual ambiguity, with low testosterone and AMH serum levels and persistence of Müllerian derivatives. AMH immunoreactivity was conserved in premeiotic seminiferous tubules of dysgenetic testes, and also in sex-cord cells of a gonadoblastoma. In patients with asymmetric gonadal differentiation, the streak gonad was AMH-negative. In conclusion, secretion of AMH is a constitutive feature of the immature Sertoli cell and its expression is altered only by mutations of the AMH gene, but not by gonadal dysgenesis. The degree of regression of Müllerian ducts and serum AMH levels reflect the number, not the functional value, of Sertoli cells present in the immature testis.


Mechanisms of disease: understanding resistance to HER2-targeted therapy in human breast cancer.
Trastuzumab is a monoclonal antibody targeted against the human epidermal growth factor receptor (HER) 2 tyrosine kinase receptor, which is overexpressed in approximately 25% of invasive breast cancers. The majority of patients with metastatic breast cancer who initially respond to trastuzumab, however, demonstrate disease progression within 1 year of treatment initiation. Preclinical studies have indicated several molecular mechanisms that could contribute to the development of trastuzumab resistance. Increased signaling via the phosphatidylinositol 3-kinase/Akt pathway could contribute to trastuzumab resistance because of activation of multiple receptor pathways that include HER2-related receptors or non-HER receptors such as the insulin-like growth factor 1 receptor, which appears to be involved in a cross-talk with HER2 in resistant cells. Additionally, loss of function of the tumor suppressor PTEN gene, the negative regulator of Akt, results in heightened Akt signaling that leads to decreased sensitivity to trastuzumab. Decreased interaction between trastuzumab and its target receptor HER2, which is due to steric hindrance of HER2 by cell surface proteins such as mucin-4 (MUC4), may block the inhibitory actions of trastuzumab. Novel therapies targeted against these aberrant molecular pathways offer hope that the effectiveness and duration of response to trastuzumab can be greatly improved.


Fine mapping of progressive pseudorheumatoid dysplasia: a tool for heterozygote identification.
Progressive pseudorheumatoid dysplasia is a skeletal genetic disorder affecting primarily the articular cartilage, causing joint stiffness and leading to a crippling status. More than two-thirds of the reported patients belong to Arab and Mediterranean populations. The disease locus has been mapped to chromosome 6q22 in a region of 12.9 cM using a Jordanian family. We examined two additional families, one Jordanian and one Palestinian, to test for homogeneity of the disorder and the presence of a common haplotype, to fine map the disorder, and to use all the information to derive a tool for heterozygote identification. The two families showed linkage to the same previously reported locus, thus suggesting homogeneity, but they did not share a common haplotype. They also provided information that refined the genetic region for the disease locus to 2.1 cM with three microsatellite markers. The absence of a common haplotype indicates that no common ancestor mutations were inherited by our patients. Genotyping for the three-marker haplotype showed that it can be used as a heterozygote identification tool.


[Suburethral cyst. A case report].
Suburethral cysts are rare, are formed from remnants of embryonic or blockage of the paraurethral glands, whose location in more than 85% of cases are found in the proximal two thirds and posterior and lateral to the urethra. The diagnosis is clinical and radiological studies are needed to demonstrate the absence of communication with the urethra. Once the diagnosis of suburethral cyst, surgery is the treatment of choice. Before its resection, the presence of a urethral diverticulum. Urethral injury is the most common surgical risk, as noted during surgery must be repaired immediately. So far it has not been reported urethra-vaginal fistula as a complication after repair. The present patient had a cyst in the distal third of Suburethral 4 x 2 cm, a 6-month follow-up remained asymptomatic, with no postoperative complication. The pathology reported wall 3 x 2.2 cm with a thickness of 0.3 cm, greyish, irregular, soft consistency. Microscopically identified transitional epithelium and foci of squamous metaplasia and focal chronic inflammation. According to the histopathological report, the transitional epithelium indicates the cyst Skene.


Serological analysis of tumor antigens in malignant glioma patients.
Sera from 27 malignant glioma patients were tested for antibodies to surface antigens of cultured human glioma cells using enzyme-linked immunosorbent assay. Average antibody titer for glioma cell lines was 0.558 +/- 0.123, which was significantly higher than in the normal control group (0.165 +/- 0.082). Surprisingly, average antibody titer for autologous glioma cells was low (0.207 +/- 0.154) in these patients. The results suggest that various surface antigens in glioma cells include specific autologous antigens, antigens associated with gliomas, and common antigens present on cultured normal and malignant cells. These analyses are important in the evaluation of monoclonal antibodies and explanation of escape mechanisms.


Transitions in Discrete Absorption Bands of Au130 Clusters upon Stepwise Charging by Spectroelectrochemistry.
Rich and tunable physicochemical properties make noble metal clusters promising candidates as novel nanomolecules for a variety of applications. Spectroelectrochemistry analysis is employed to resolve previously inaccessible electronic transitions in Au130 clusters stabilized by a monolayer of di- and monothiolate ligands. Well-defined quantized double-layer charging of the Au core and oxidizable ligands make this Au130 nanocluster unique among others and enable selective electrolysis to different core and ligand charge states. Subsequent analysis of the corresponding absorption changes reveals that different absorption bands originate from different electronic transitions involving both metal core energy states and ligand molecular orbitals. Besides the four discrete absorption bands in the steady-state UV-visible-near-IR absorption spectrum, additional transitions otherwise not detectable are resolved upon selective addition/removal of electrons at cores and ligand energy states, respectively, upon electrolysis. An energy diagram is proposed that successfully explains the major features observed in electrochemistry and absorption spectroscopy. Those assignments are believed applicable and effective to explain similar transitions observed in some other Au thiolate clusters.


Low-Cost and Scaled-Up Production of Fluorine-Free, Substrate-Independent, Large-Area Superhydrophobic Coatings Based on Hydroxyapatite Nanowire Bundles.
To date, the scaled-up production and large-area applications of superhydrophobic coatings are limited because of complicated procedures, environmentally harmful fluorinated compounds, restrictive substrates, expensive equipment, and raw materials usually involved in the fabrication process. Herein, the facile, low-cost, and green production of superhydrophobic coatings based on hydroxyapatite nanowire bundles (HNBs) is reported. Hydrophobic HNBs are synthesised by using a one-step solvothermal method with oleic acid as the structure-directing and hydrophobic agent. During the reaction process, highly hydrophobic C-H groups of oleic acid molecules can be attached in situ to the surface of HNBs through the chelate interaction between Ca2+ ions and carboxylic groups. This facile synthetic method allows the scaled-up production of HNBs up to about 8 L, which is the largest production scale of superhydrophobic paint based on HNBs ever reported. In addition, the design of the 100 L reaction system is also shown. The HNBs can be coated on any substrate with an arbitrary shape by the spray-coating technique. The self-cleaning ability in air and oil, high-temperature stability, and excellent mechanical durability of the as-prepared superhydrophobic coatings are demonstrated. More importantly, the HNBs are coated on large-sized practical objects to form large-area superhydrophobic coatings.


[Cytosine deaminase and thymidine kinase double suicide gene system driven by carcinoembryonic antigen promoter for the treatment of colorectal carcinoma xenograft in nude mice].
To explore the therapeutic efficacy of double suicide gene system driven by carcinoembryonic antigen (CEA) promoter (Cp-CDglyTK) on colorectal carcinoma xenograft in nude mice. The plasmid pcDNA3.1(-)Cp-CDglyTK was transfected into the CEA-positive SW480 and CEA-negative HeLa cells respectively. The expression of suicide gene was detected by RT-PCR. And the transfected cells were treated with 5-fluorocytosine (5-FC) and ganciclovir (GCV) at different concentrations and the cell-killing and bystander effects assayed by methyl thiazolyl tetrazolium (MTT). By a transplantation of cultivated cells, SW480 or HeLa cell lines were injected subcutaneously into right axillary of nude mice to establish 96 SW480 and 72 HeLa tumor animal models. Nude mice were completely randomized with statistical software according to tumor volume. For prodrug therapy, 48 SW480-bearing mice were divided equally into 4 groups of I-IV. At the same time, 48 HeLa-bearing mice were divided equally into 4 groups of V-VIII. Groups I & V received an intratumoral injection of PBS, groups II & VIGCV and 5-FC intratumorally, groups III & VII PBS intraperitoneally and groups IV & VIII GCV and 5-FC intraperitoneally. Forty-eight SW480-bearing mice were divided equally into 4 groups of IX∼XII and 24 Hela-bearing ones into groups of & in therapy experiment by suicide gene plus prodrug. Six groups received an intratumoral injection of liposome Lipofectamine and plasmid CP-CDglyTK and then an intraperitoneal injection of drug. The groups of IX and received an injection of PBS, group X GCV, group XI 5-FC and groups XII & GCV and 5-FC. The observation parameters included tumor bulk, tumor weight, survival time and treatment effect in each group. SW480 cells transfected by plasmid pcDNA3.1(-)Cp- CDglyTK expressed CDglyTK gene. The inhibition rates of GCV and 5-FC were significantly higher than those of HeLa cells (59.87% ± 0.21% vs 9.90% ± 0.09%, P < 0.01). And higher inhibition rates and stronger bystander effect existed in double versus single produg (all P < 0.05). Tumor size, final tumor weight and survival time of nude mice in groups ofII, IV, VI & VIII had no significant difference with groups ofI, III, V & VII (all P < 0.05). Final tumor size and weight of group XII was significantly smaller than those of groups of IX, X and XI ((150.0 ± 3.2) vs (522.5 ± 1.9) and (256.8 ± 10.4) and (260.7 ± 2.2) mm(3), (54.1 ± 10.4) vs (682.0 ± 12.0) and (251.8 ± 15.1) and (271.6 ± 17.7) mg, all P < 0.05). Meanwhile, the tumor inhibition rate and survival time of group XII(92.1% and (25.7 ± 0.8)d) were significant higher and longer than group X (63.1% and (21.8 ± 0.5) d) and group XI (60.2% and (18.0 ± 0.9) d) (all P < 0.05). However, no significant difference existed in tumor size, final tumor weight and survival time between groups and (all P > 0.05). The inhibition rate of group was merely 0.9%. CDglyTK double suicide gene system driven by CEA promoter may inhibit CEA positive colorectal cancer xenograft in prodrug-treated nude mice.


Self-assembly of a group I intron active site from its component tertiary structural domains.
The catalytic core of Group I self-splicing introns has been proposed to consist of two structural domains, P4-P6 and P3-P9. Each contains helical segments and conserved unpaired nucleotides, and the isolated P4-P6 domain has been shown to have substantial native tertiary structure. The proposed tertiary structure domains of the Tetrahymena intron were synthesized separately and shown to self-assemble into a catalytically active complex. Surprisingly, the concentration dependence of these reactions revealed that the domains interact with nanomolar apparent dissociation constants, even though there is no known base pairing between P4-P6 and P3-P9. This suggests that the domains interact through multiple tertiary contacts, the nature of which can now be explored in this system. For example, a circularly permuted version of the P4-P6 domain, which folds similarly to the native P4-P6 molecule, formed a stable but inactive complex. Interestingly, activity was demonstrated with the permuted molecule when nucleotides proposed to form a triple-strand interaction with P4 and P6 were restored as part of the P1-P3 substrate or as part of the P3-P9 RNA. Thus, beyond stabilization of the P4-P6 domain, the triple-strand region may facilitate correct orientation of the RNA domains or participate more directly in catalysis.


Baricitinib: The First Jak Inhibitor Approved in Europe for the Treatment of Moderate to Severe Atopic Dermatitis in Adult Patients.
Background: Atopic dermatitis (AD) is an inflammatory skin disease characterized by a wide phenotypic variety with a very complex pathophysiological mechanism that has led to the identification of new therapeutic targets, such as janus kinasis (JAK) inhibitors. Objectives: To evaluate the efficacy and safety of baricitinib, the first JAK 1 and 2 inhibitor approved in Europe for the treatment of adult patients with moderate-to-severe AD. Methods: The efficacy and safety data available from the Phase III studies belonging to the BREEZE AD program are presented. Results: Results from BREEZE-AD1, AD2, AD4, and AD7 showed the efficacy of Baricitib 4 mg, administered orally, once daily, as monotherapy or in combination with topical corticosteroid (TCS), with a significant proportion of patients achieving primary endpoints IGA 0-1 (16.4% vs. 4.8%; 13.8% vs. 4.5%; 21.7% vs. 9.7%; 30.6% vs. 14.7%) and EASI75 (24.8% vs. 8.8%; 21.1% vs. 6.1%; 31.5% vs. 17.2%; 47.7% vs. 22.9%) at week 16 (W16) compared to placebo, respectively. Baricitinib showed rapid improvement in symptoms, starting from week 1 of treatment at 4 mg dosage, with a good safety profile. Nasopharyngitis, upper respiratory tract infections (URIs), creatine phosphokinase (CPK) elevations, and headache were the most frequently reported adverse events. Conclusions: Following the efficacy and safety data on W 16 from the phase III BREEZE-AD studies, baricitinib has recently been approved in Europe for the treatment of moderate to severe AD in adult patients. Further data to evaluate long-term efficacy and safety in a real-life setting are needed.


Is surgical intervention in acute cholecystitis in pregnancy justified?
Over a three-year period 49 cases were admitted to our hospital with an acute abdomen in pregnancy due to cholecystitis. In this article we compare surgical treatment with medical treatment and consider the aetiology of the high prevalence. Out of the 49 cases admitted, 15 cases (31%) had emergency cholecystectomy within the first week and 34 cases (69%) were treated conservatively of whom 24 relapsed many times and had to be readmitted to the hospital (mean number of admissions was 4 +/- 1.4 and the mean hospital stay was 8 +/- 2.3 days) and of the remaining 10 on conservative management, three had emergency cholecystectomy and seven reached term safely. The maternal morbidity is significantly less in the surgically treated group (P < 0.0001) but the perinatal outcome failed to show any significant difference. The frequency of acute cholecystitis in pregnancy (0.33%) is high in comparison with other studies. Although tocolytics were used in 13 cases they did not improve the fetal outcome significantly and had maternal and fetal side effects. In conclusion early surgical intervention is recommended and the use of tocolytics did not improve the perinatal outcome.


Small angle x-ray scattering with a beryllium compound refractive lens as focusing optic.
At BW4 at HASYLAB a beryllium compound refractive lens (Be-CRL) is used for the focusing in small-angle x-ray scattering experiments. Using it provides the advantages of higher long-term stability and a much easier alignment compared to a setup with focusing mirrors. In our investigations presented here, we show the advantages of using a Be-CRL in small-angle and also ultra small-angle x-ray scattering. We investigated the beam characteristics at the sample position with respect to spot size and photon flux. The spot size is comparable to that of a setup with focusing mirrors but with a gain in flux and better long-term stability. It is also shown that plane mirrors are still necessary to suppress higher order energies passing the monochromator.


Embryonic stem cells in cattle.
Because of the potential use of embryonic stem cells (ESC), especially for genetic modifications, there is great interest in establishing domestic animals-related ESCs. Unfortunately, despite considerable efforts, validated ESC lines in species other than mice and primates are yet to be isolated. In this paper, we will summarize the current knowledge on bovine ESCs in an attempt to understand why derivation of domestic animal ESC is still unsuccessful and we will discuss some promising future approaches.


Experimental and model investigations of bleaching and saturation of fluorescence in flow cytometry.
We investigated the fluorescence emission from three fluorophores commonly used for labeling cells in flow cytometry. We have demonstrated that the fluorescence emission from cells labeled with fluorescein-isothiocyanate (FITC), phycoerythrin (PE), and allophycocyanin (APC) is considerably saturated and bleached in standard flow cytometric conditions. Therefore, for optimization of fluorescence detection in a flow cytometer, it is important to know the emission kinetics in detail. We made a mathematical model of the optical processes involved: absorption, fluorescence emission, nonradiative decay, photodestruction, and triplet state occupation. The validity of the model was experimentally tested with a set of averaged fluorescence pulses, measured in a large range of intensities and illumination times. The fluorescence of APC could be completely described by the model and produced the following rate constants: photodestruction rate kb1 = 6 x 10(3) s(-1), triplet state population rate k12 = 2 x 10(5) s(-1), and depopulation rate k20 = 5 x 10(4) s(-1). The fluorescence kinetics of FITC- and PE-labeled cells could not be fitted with only three parameters over the entire range, indicating that other optical processes are involved. We used the model to determine the sensitivity of our flow cytometer and to calculate the optimum conditions for the detection of APC. The results show that in principle a single APC molecule on a cell can be detected in the presence of background, i.e., autofluorescence and Raman scattering by water.


Acute Subdural Hematoma Complicating Heparin-induced Thrombocytopenia: A Case Report.
Heparin-induced thrombocytopenia (HIT) is an antibody-mediated drug reaction to heparin use that causes platelet aggregation, followed by thrombocytopenia. Despite the thrombocytopenia, the main complications of HIT are thromboembolic in nature rather than hemorrhagic, and in particular, intracranial hemorrhage is rare. Herein, we describe a case of atraumatic acute subdural hematoma secondary to HIT, which was treated by platelet transfusion and surgery. A 77-year-old woman was admitted to our hospital for the treatment of severe aortic valve stenosis. Unfractionated heparin was administered during the preoperative period and during the aortic valve replacement surgery. Three days after the cardiac surgery, the patient presented with coma consistent with an acute subdural hematoma in the posterior fossa and obstructive hydrocephalus. Laboratory examination revealed a marked decrease of the platelet count to 40000/µL, and subsequent serological assay confirmed the diagnosis of HIT. The patient was treated by transfusion of platelets and fresh frozen plasma, and surgical removal of the hematoma. We started the administration of argatroban for substitution of heparin 4 days after the craniotomy. On day 13 after the neurosurgery, the patient developed cerebral infarction due to left middle cerebral artery occlusion and persistent right hemiparesis. We presented a rare case of the patient who developed acute subdural hematoma complicating HIT. Emergency craniotomy was successfully performed after administering platelet transfusions. Our experience with the present case suggests that platelet transfusions may be effective for performing emergency surgery for intracranial hemorrhage, even in patients with HIT.


[A case of rheumatoid factor-positive pachymeningitis].
We report a case of rheumatoid pachymeningitis involving the posterior fossa. A 71-year-old woman presented with headache, vertigo and dizziness. MRI demonstrated hypertrophic masses in the meninges of the left cerebellar tentorium, cerebellopontine angle and the fourth ventricle. Six months of treatment with betamethasone, prednisolone and azathioprine improved the patient's neurological status. Because an inappropriate immune process and systemic immune disease may cause idiopathic pachymeningitis, the performance of immunological studies for idiopathic cases is mandatory.


"Plugged" Anterior Inferior Cerebellar Artery Aneurysm Causing Facial Palsy, Hearing Loss, and Subarachnoid Hemorrhage Treated by a Translabyrinthine Approach.
Anterior inferior cerebellar artery (AICA) aneurysms are rare, less than 1%-2% of all intracranial aneurysms. Aneurysms of the distal AICA are even less common and can present with hearing loss and facial paralysis because of their relationship with the internal auditory canal (IAC). A 65-year-old male was followed for fluctuating left facial weakness and left-sided hearing loss for over a year. Serial magnetic resonance imaging (MRI) scans showed a mass near the left IAC, thought to be a vestibular schwannoma. Just prior to his next clinic visit, the patient deteriorated suddenly from a subarachnoid hemorrhage. Cerebral angiography revealed a 5.5 mm saccular aneurysm at the distal left AICA, which was clip ligated via a translabyrinthine (TL) approach. The patient had a good functional outcome (modified Rankin Scale [mRS] 1) after 30 days despite persistent left facial weakness. Stable obliteration of the aneurysm was demonstrated by cerebral angiography postoperatively. Distal AICA aneurysms are rare and can have a similar presentation to tumors in the cerebellar pontine angle. Because of the unique anatomy of the distal AICA, open clip ligation via a TL approach is an effective method to secure these aneurysms.


Erythroid cell fusion in the early phase of Friend virus leukemogenesis.
Infection of susceptible strain mice with the oncogenic Friend erythroleukemia virus initially results in fulminant erythroid hyperplasia. Several weeks later a frank erythroid leukemia develops. At the earliest stages of Friend disease there is extensive cell fusion involving erythroid cells but not platelets and granulocytes. Fusion was detected in experiments with allophenic (chimeric) mice whose component strains express electrophoretically distinct forms of the dimeric enzyme glucose phosphate isomerase (GPI). Infection of such animals with the polycythemic strain of Friend virus resulted in the rapid development of Friend disease. Concomitant with the appearance of early disease symptoms was the appearance in the red cells of the heterodimeric form of GPI, an unequivocal consequence of cell fusion. Platelet and granulocyte samples from the same infected animals failed to exhibit the hybrid GPI form. Furthermore, no hybrid dimer was evident in red cells from chimeric mice in which blood formation had been stimulated by phenylhydrazine treatment. These observations suggest that the occurrence of cell fusion early after infection by Friend virus is a significant aspect in the rapid development of neoplastic disease.


Alternative cybex exercise positions.
Many alternative exercise positions are possible with the Cybex(R). The most practical of these positions are presented. Clinicians are encouraged to test and adopt these variations if they are deemed appropriate and useful for their facility and patient clientele. J Orthop Sports Phys Ther 1985;7(2):73-76.


ADAP plays a pivotal role in CD4+ T cell activation but is only marginally involved in CD8+ T cell activation, differentiation, and immunity to pathogens.
The adhesion and degranulation promoting adaptor protein (ADAP) is a multifunctional scaffold involved in many different signaling pathways that are important for the function of T cells, including the inside-out and outside-in signaling of integrins, the activation of NF-κB, and the subsequent production of proinflammatory cytokines (e.g., IFN-γ and IL-2). Strikingly, despite its well-established role in T cells, previous studies did not distinguish between CD4+ and CD8+ T cells, and thus, it is unknown whether ADAP fulfills equally important functions in both T cell subsets. We show here that despite comparable ADAP expression levels in CD4+ and CD8+ T cells, their function is differentially dependent on ADAP. Whereas in vitro TCR-stimulation experiments revealed that activation, proliferation, and adhesion are severely compromised in CD4+ T cells lacking ADAP, their CD8+ counterparts are hardly affected by ADAP deficiency. Accordingly, antigen-specific in vivo stimulation of adoptively transferred CD8+ T cells during Listeria monocytogenes (Lm) and influenza A virus (IAV) infection revealed only moderate effects of ADAP deficiency in terms of CD8+ T cell activation, proliferation, and differentiation, which, however, did not impair pathogen-specific immunity. Thus, we show for the first time that ADAP fulfills different functions in CD4+ and CD8+ T cells, with CD8+ T cells being less dependent on ADAP. Our data identify ADAP as a potential molecular target for T cell subset-specific therapeutic interventions.


Biomechanical testing of cadaveric specimens: importance of bone mineral density assessment.
The bone density of cadaveric specimens is highly variable and has a significant effect on the results of biomechanical testing but it is not often assessed before testing is performed in the lab. Bone mineral density (BMD) tests such as dual X-ray absorptiometry (DXA) are widely available, easy to perform and correlate highly and significantly with bone strength in many modes of failure. We present the results of two different studies performed on cadaveric foot and ankle specimens. In these studies the results vary significantly according to BMD, and this effect is not always eliminated with the use of matched pairs of cadaveric specimens.


[Determination of the antioxidant properties of the blood and their diagnostic significance in the elderly].
Blood antioxidant system parameters were examined in elderly subjects. The authors have developed methods for measurements of catalase, superoxide dismutase, and lipid peroxidation products. They introduce a new factor 'F' that is supposed to characterize the blood antioxidant system; this factor is based on the values of catalase and superoxide dismutase activities and the intensity of lipid peroxidation. The authors come to a conclusion that the blood antioxidant and oxidant systems may be more accurately described with the use of this new factor F. In case of an abdominal tumor whole blood catalase level is elevated and superoxide dismutase activity significantly reduced. Factor F values were found extremely low before death, therefore this factor may be considered an important criterion of a critical state. The blood antioxidant parameters of patients with diabetes mellitus and essential hypertension did not much differ from those of age-matched healthy subjects.


Discrepancies between two automated immunoassay systems in determining hepatitis B virus markers in serum samples with concomitant presence of antigens and antibodies.
This study compared the assay results of HBV markers obtained with two automated immunoassay systems in serum samples with concomitant HBV antigens and antibodies. Eighty-nine samples of concomitant HBsAg and anti-HBs and 74 samples of concomitant HBeAg and anti-HBe were analyzed by the Abbott Architect i2000 and the Roche Elecsys 2010 immunoassay systems. The overall concordance rates of the Architect and Elecsys results were 78.6% for samples with concomitant HBsAg and anti-HBs and 77% for samples with concomitant HBeAg and anti-HBe. The data show that substantial differences exist between the results obtained by these two systems, especially in determining anti-HBs and HBeAg at low concentrations.


Applications of liquid chromatography coupled to mass spectrometry-based metabolomics in clinical chemistry and toxicology: A review.
The metabolome is the set of small molecular mass organic compounds found in a given biological media. It includes all organic substances naturally occurring from the metabolism of the studied living organism, except biological polymers, but also xenobiotics and their biotransformation products. The metabolic fingerprints of biofluids obtained by mass spectrometry (MS) or nuclear magnetic resonance (NMR)-based methods contain a few hundreds to thousands of signals related to both genetic and environmental contributions. Metabolomics, which refers to the untargeted quantitative or semi-quantitative analysis of the metabolome, is a promising tool for biomarker discovery. Although proof-of-concept studies by metabolomics-based approaches in the field of toxicology and clinical chemistry have initially been performed using NMR, the use of liquid chromatography hyphenated to mass spectrometry (LC/MS) has increased over the recent years, providing complementary results to those obtained with other approaches. This paper reviews and comments the input of LC/MS in this field. We describe here the overall process of analysis, review some seminal papers in the field and discuss the perspectives of metabolomics for the biomonitoring of exposure and diagnosis of diseases.


Where are we now: assessing the price, availability and affordability of essential medicines in Delhi as India plans free medicine for all.
Inequitable access to medicines is a major weakness in the Indian health care system. Baseline data needed to develop effective public health policy and provide equitable access to essential medicines. The present survey was conducted to investigate the price, availability, and affordability of fifty essential medicines in the public and private sector in Delhi, India using standardized WHO/HAI methodology. Data on procurement price and availability was collected (July-October 2011) from three public healthcare providers: the federal (central) government, state government and Municipal Corporation of Delhi (MCD). Data on price and availability of medicines was collected from private retail and chain pharmacies of a leading corporate house. Prices were compared to an international reference price (expressed as median price ratio-MPR). The procurement price of surveyed medicines was 0.53-0.82 times the international reference price-IRP. However, the overall mean availability of surveyed medicines in facilities under state government and MCD was 41.3% and 23.2%, respectively. The overall mean availability of medicines in three tertiary care facilities operated by the federal government was 49.3%. Availability of generic medicines was much higher in the private sector. Off-patented medicines, like diazepam, diclofenac, and doxycycline had the highest MPRs. The price ratio between procurement and retail was as high as 28 (range 11-28) for certain medicines. Seven-day treatment with a popular brand of amoxicillin+clavulanic acid or one inhaler each of budesonide and salbutamol cost 2.3 and 1.4 days' wages for the lowest paid government worker. A majority of India's population cannot afford these prices. This study revealed that procurement prices of surveyed medicines were reasonable in comparison to IRP. However, variation in procurement prices of certain medicines by different public procurement agencies was noted. Availability of medicines was very poor in public sector facilities, which are the primary source of free medicines for a majority of India's low-income population. Availability of medicines is better in private retail pharmacies but affordability remains a big challenge for a majority of the population. These data have significant policy implications that could help in amending policies to increase the access to essential medicines for India's population.


Pioneer Axon Navigation Is Controlled by AEX-3, a Guanine Nucleotide Exchange Factor for RAB-3 in Caenorhabditis elegans.
Precise and accurate axon tract formation is an essential aspect of brain development. This is achieved by the migration of early outgrowing axons (pioneers) allowing later outgrowing axons (followers) to extend toward their targets in the embryo. In Caenorhabditis elegans the AVG neuron pioneers the right axon tract of the ventral nerve cord, the major longitudinal axon tract. AVG is essential for the guidance of follower axons and hence organization of the ventral nerve cord. In an enhancer screen for AVG axon guidance defects in a nid-1/Nidogen mutant background, we isolated an allele of aex-3 aex-3 mutant animals show highly penetrant AVG axon navigation defects. These defects are dependent on a mutation in nid-1/Nidogen, a basement membrane component. Our data suggest that AEX-3 activates RAB-3 in the context of AVG axon navigation. aex-3 genetically acts together with known players of vesicular exocytosis: unc-64/Syntaxin, unc-31/CAPS, and ida-1/IA-2. Furthermore our genetic interaction data suggest that AEX-3 and the UNC-6/Netrin receptor UNC-5 act in the same pathway, suggesting AEX-3 might regulate the trafficking and/or insertion of UNC-5 at the growth cone to mediate the proper guidance of the AVG axon.


MEERCAT: Multiplexed Efficient Cell Free Expression of Recombinant QconCATs For Large Scale Absolute Proteome Quantification.
A major challenge in proteomics is the absolute accurate quantification of large numbers of proteins. QconCATs, artificial proteins that are concatenations of multiple standard peptides, are well established as an efficient means to generate standards for proteome quantification. Previously, QconCATs have been expressed in bacteria, but we now describe QconCAT expression in a robust, cell-free system. The new expression approach rescues QconCATs that previously were unable to be expressed in bacteria and can reduce the incidence of proteolytic damage to QconCATs. Moreover, it is possible to cosynthesize QconCATs in a highly-multiplexed translation reaction, coexpressing tens or hundreds of QconCATs simultaneously. By obviating bacterial culture and through the gain of high level multiplexing, it is now possible to generate tens of thousands of standard peptides in a matter of weeks, rendering absolute quantification of a complex proteome highly achievable in a reproducible, broadly deployable system.


Glycemic control in type 2 diabetes: time for an evidence-based about-face?
Some diabetes guidelines set low glycemic control goals for patients with type 2 diabetes mellitus (such as a hemoglobin A(1c) level as low as 6.5% to 7.0%) to avoid or delay complications. Our review and critique of recent large randomized trials in patients with type 2 diabetes suggest that tight glycemic control burdens patients with complex treatment programs, hypoglycemia, weight gain, and costs and offers uncertain benefits in return. We believe clinicians should prioritize supporting well-being and healthy lifestyles, preventive care, and cardiovascular risk reduction in these patients. Glycemic control efforts should individualize hemoglobin A(1c) targets so that those targets and the actions necessary to achieve them reflect patients' personal and clinical context and their informed values and preferences.


Discontinuation of octreotide LAR after long term, successful treatment of patients with acromegaly: is it worth trying?
Somatostatin analogs (SA) have been used for over 25 years in the treatment of acromegaly. A major disadvantage is the need to continue therapy indefinitely. To evaluate the feasibility of discontinuing therapy in well-controlled patients with acromegaly treated chronically with SA. Of the 205 subjects on octreotide LAR, we selected those who met the following criteria: two or more years of treatment, a stable dose and injection interval of 20 mg every 8 weeks or longer for the previous year, no history of radiation, no cabergoline for the previous 6 months, a GH <1.5 ng/ml, and an IGF1 <1.2×upper limit of normal (ULN). Octreotide LAR was stopped and both GH and IGF1 were measured monthly for 4 months; a glucose-suppressed GH value and magnetic resonance imaging were obtained at the 4th month, thereafter, basal GH and IGF1 were measured q. 3 months, for 12-18 months. Patients were removed from the study if GH or IGF1 rose to 1.5 ng/ml or 1.2×ULN respectively. Twelve patients (ten women, mean age 48±13 years) were studied. Seven patients (58.3%) relapsed biochemically within 1 year of having stopped the SA; two patients relapsed by GH and IGF1 criteria, the remaining five patients kept GH levels within target. Five patients (41.7%) remain in remission after 12 months of follow-up. Non-recurring patients were on longer injection intervals but no other characteristic was associated with a successful withdrawal. Withdrawal of SA is possible in a small but distinct subset of patients, particularly in those who are very well controlled on relatively low doses administered at long intervals.


Does clofazimine have a prophylactic role against neuritis?
A study was undertaken with the aim of testing the usefulness of clofazimine as a prophylactic agent against neuritis and nerve damage. A modified regimen, using initial high doses of clofazimine followed by regular multibacillary multidrug therapy (MB-MDT) WHO regimen, was given to a series of consecutive cases of high risk borderline leprosy patients, fulfilling defined selection criteria (n = 65). These patients were studied for the incidence of neuritis/Type I reaction, over a period of 2 years. Results were compared with a matched series of consecutive cases treated only with regular MB-MDT WHO regimen (n1 = 57). The difference in incidence rates of neuritis between the two groups was significant (p < 0.01), suggesting that clofazimine may have a useful prophylactic role against neuritis/Type I reaction and nerve damage.


Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI.
We have characterized a new selenium-dependent glutathione peroxidase, GSHPx-GI, by expressing a GSHPx-GI cDNA isolated from human hepatoma HepG2 cells in human mammary carcinoma MCF-7 cells, which have virtually undetectable expression of either the classical cellular enzyme, GSHPx-1, or GSHPx-GI at the protein level. One of the G418-resistant clones, neo-D1, expresses the transfected GSHPx-GI cDNA. This is based on 1) the presence of an additional GSHPx-GI DNA restriction fragment detected by Southern analysis; 2) the presence of a 1.9-kilobase (kb) GSHPx-GI mRNA in addition to the 1.0-kb endogenous mRNA by Northern analysis; and 3) the appearance of a 22-kDa 75Se-labeled protein which is absent in parental MCF-7 cells revealed by SDS-polyacrylamide gel electrophoresis. GSHPx-GI expressed in neo-D1 is a tetrameric protein localized in cytosol. GSHPx-GI does not cross-react with antisera against human GSHPx-1 or human plasma glutathione peroxidase (GSHPx-P). Similar substrate specificities are found for GSHPx-1 and GSHPx-GI; they both catalyze the reduction of H2O2, tert-butyl hydroperoxide, cumene hydroperoxide, and linoleic acid hydroperoxide with glutathione, but not of phosphatidylcholine hydroperoxide. GSHPx-GI mRNA was readily detected in human liver and colon, and occasionally in human breast samples, but not other human tissues including kidney, heart, lung, placenta, or uterus. In rodent tissues, GSHPx-GI mRNA is only detected in the gastrointestinal tract, and not in other tissues including liver. In fact, GSHPx-GI appears to be the major glutathione-dependent peroxidase activity in rodent GI tract. This finding suggests that GSHPx-GI could play a major role in protecting mammals from the toxicity of ingested lipid hydroperoxides. In conclusion, we have demonstrated that GSHPx-GI is the fourth member in the selenium-dependent glutathione peroxidase family, in addition to GSHPx-1, GSHPx-P, and phospholipid hydroperoxide glutathione peroxidase (PHGPX).


Telomere protein complexes and their role in lymphoid malignancies.
Telomeres are highly regulated and dynamic complexes that protect the genomic DNA and prevent the end of linear chromosomes from being misrecognized as a broken DNA. Due to the end replication problem, telomeres of somatic cells shorten with each cell division, inducing cell senescence. Telomerase is a reverse transcriptase capable of compensating telomere attrition by adding telomere repeats to the ends of chromosomes. Human telomeres are associated with the shelterin complex which consists of six telomere-associated proteins that specifically bind to telomeric DNA. Alterations or removal of individual shelterin components would lead to telomere uncapping and telomere dysfunction, resulting in cellular senescence and transformation to a malignant state. Another complex of multifunctional proteins, named non-shelterin complex, is thought to prevent telomere degradation and facilitate telomerase-based telomere elongation. As telomerase is highly expressed in most human tumor cells, it is considered an attractive target for new therapeutic strategies. In this review, we will summarize the characteristics of telomeres and telomerase in lymphoid malignancies and discuss the role of telomere-associated proteins in these entities.


Preschoolers' mental rotation of letters: Sex differences in hemispheric asymmetry.
Adults' mental rotation performance has been found to produce one of the largest sex differences in cognition accompanied by sex differences in functional cerebral asymmetry. In this study sex differences in mental rotation of letters were investigated with children as young as five years. Based on the electrophysiological brain correlates of mental rotation, we observed a bilateral brain activity for preschool girls whereas the preschool boys' brain activity was clearly lateralized towards the right hemisphere if and only if mental rotation was needed to solve the task. At the same time, we did not find any sex differences in mental rotation speed or accuracy. Thus, sex differences in functional hemispheric asymmetry during mental rotation do not require hormonal changes that occur during puberty.


Less aggressive treatment of neonatal jaundice and reports of kernicterus: lessons about practice guidelines.
The publication of guidelines calling for less aggressive treatment of jaundice in newborns has been followed by a reappearance of case reports of kernicterus. These case reports illustrate important issues for writers and consumers of practice guidelines. One issue is the particular salience of identified patients with bad outcomes, and their potentially disproportionate influence on decision-makers. A second issue is whether, when good evidence of treatment benefit is lacking, policymakers should recommend what has traditionally been done, recommend less treatment, or not make recommendations at all. Finally, the cases raise the question of whether treatment guidelines should be more conservative than their authors actually believe is necessary, to take into account the likelihood that they will not be closely followed. We believe that case reports can serve as an important early warning system, but policymakers should be aware of their potentially disproportionate influence. In the long run, patients and clinicians will be best served by guidelines that summarize and acknowledge the limitations of existing evidence, that allow a wide range of treatment options when evidence is weak, and that recommend what the guideline authors actually believe should be done. In the short run a period of readjustment may be required, however, as clinicians become accustomed to guidelines written to be followed, rather than bent.


Technology and Humanity.
New technologies have brought immeasurable benefits to medicine. They have also altered our patients' experiences and our role as providers in significant ways. To give you an example, my patient sessions often start with me madly clicking away in the electronic health record, trying to reconcile three duplicate instances of the same medication in the patient's chart. After that maze, a series of pop-up boxes flash alerts to query the patient about weight, smoking, depression, and pain. I am now clicking as fast as I can to preserve any remaining time in the 15-minute session to address the patient's cancer. And, all of this is happening with my back to the patient!


Water transport mechanism through open capillaries analyzed by direct surface modifications on biological surfaces.
Some small animals only use water transport mechanisms passively driven by surface energies. However, little is known about passive water transport mechanisms because it is difficult to measure the wettability of microstructures in small areas and determine the chemistry of biological surfaces. Herein, we developed to directly analyse the structural effects of wettability of chemically modified biological surfaces by using a nanoliter volume water droplet and a hi-speed video system. The wharf roach Ligia exotica transports water only by using open capillaries in its legs containing hair- and paddle-like microstructures. The structural effects of legs chemically modified with a self-assembled monolayer were analysed, so that the wharf roach has a smart water transport system passively driven by differences of wettability between the microstructures. We anticipate that this passive water transport mechanism may inspire novel biomimetic fluid manipulations with or without a gravitational field.


[How does thermotherapy effectively work on benign prostatic hyperplasia--an experimental study].
Isometric contractile force of rabbit prostatic tissue in response to electric field stimulation (EFS), KCl, and phenylephrine were measured at incubation temperature of 37 degrees C, before and after thermal exposure to 42 degrees C, 45 degrees C, 48 degrees C and 50 degrees C for 30 minutes. The contractile force in response to EFS decreased after thermal exposure above 45 degrees C, and the contractile force in response to KCL or phenylephrine decreased after thermal exposure above 48 degrees C. All the contractile response abolished after thermal exposure to 50 degrees C. The results indicate that the nerve is more hear-sensitive than the smooth muscle in the prostate. Histological examination revealed shrinkage of cell body and dark staining of nuclear chromatin of the smooth muscle cells after thermal exposure above 48 degrees C. The same histological change of the smooth muscle as well as degenerative change of the nerve cells was observed on the prostate 3-7 months after clinical thermotherapy. From these results, it is suggested that clinical effect of thermotherapy is brought about from both neural and muscular damage of the prostate. Since the least temperature to cause an irreversible tissue damage ranges from 48 degrees C through 50 degrees C, we believe it is ideal to heat the prostate around 50 degrees C to obtain a good clinical effect of thermotherapy on benign prostatic hyperplasia as a minimum invasive treatment.


Managing the problem patient.
Anxiety, overtreatment, inappropriate combination therapy, and noncompliance are all characterized as prevalent etiologic factors in so-called resistant hypertension. But perhaps the most common problem that expresses itself as resistant hypertension is failure to adequately control intravascular volume. The key point is that a cause for resistance is almost always discoverable.


Covalent Binding of Antibodies to Cellulose Paper Discs and Their Applications in Naked-eye Colorimetric Immunoassays.
This report presents two methods for the covalent immobilization of capture antibodies on cellulose filter paper grade No. 1 (medium-flow filter paper) discs and grade No. 113 (fast-flow filter paper) discs. These cellulose paper discs were grafted with amine functional groups through a silane coupling technique before the antibodies were immobilized on them. Periodate oxidation and glutaraldehyde cross-linking methods were used to graft capture antibodies on the cellulose paper discs. In order to ensure the maximum binding capacity of the capture antibodies to their targets after immobilization, the effects of various concentrations of sodium periodate, glutaraldehyde, and capture antibodies on the surface of the paper discs were investigated. The antibodies that were coated on the amine-functionalized cellulose paper discs through a glutaraldehyde cross-linking agent showed enhanced binding activity to the target when compared to the periodate oxidation method. IgG (in mouse reference serum) was used as a reference target in this study to test the application of covalently immobilized antibodies through glutaraldehyde. A new paper-based, enzyme-linked immunosorbent assay (ELISA) was successfully developed and validated for the detection of IgG. This method does not require equipment, and it can detect 100 ng/ml of IgG. The fast-flow filter paper was more sensitive than the medium-flow filter paper. The incubation period of this assay was short and required small sample volumes. This naked-eye, colorimetric immunoassay can be extended to detect other targets that are identified with conventional ELISA.


Lipid peroxidation, hemolysis and antioxidant enzymes of erythrocytes in stroke.
Erythrocyte membrane lipid peroxidation and consequent percentage hemolysis and related antioxidant enzymes viz., superoxide dismutase, glutathione peroxidase, glutathione reductase and catalase were determined in 16 cases of hemorrhagic stroke and 30 cases of thrombotic stroke. The results obtained were compared with 50 age and sex matched controls. 12 thrombotic stroke patients who showed symptomatic recovery after medication were considered for follow up. Lipid peroxidation and percentage hemolysis in patients with thrombotic stroke and hemorrhagic stroke was significantly elevated when compared to controls. Glutathione reductase and superoxide dismutase levels were found to be significantly reduced in thrombotic stroke and hemorrhagic stroke respectively, when compared to healthy subjects. There was no significant difference in the other parameters when compared to controls. In post treatment thrombotic stoke, catalase and glutathione reductase levels increased significantly and oxidative hemolysis decreased compared to their pretreatment values. Thus, our results indicate considerable oxidative stress in stroke.


Incidence and characteristics of lower limb amputations in people with diabetes.
To estimate the incidence, characteristics and potential causes of lower limb amputations in France. Admissions with lower limb amputations were extracted from the 2003 French national hospital discharge database, which includes major diagnoses and procedures performed during hospital admissions. For each patient, diabetes was defined by its record in at least one admission with or without lower limb amputation in the 2002-2003 databases. In 2003, 17 551 admissions with lower limb amputation were recorded, involving 15 353 persons, which included 7955 people with diabetes. The crude incidence of lower limb amputation in people with diabetes was 378/100 000 (349/100 000 when excluding traumatic lower limb amputation). The sex and age standardized incidence was 12 times higher in people with than without diabetes (158 vs. 13/100 000). Renal complications and peripheral arterial disease and/or neuropathy were reported in, respectively, 30% and 95% of people with diabetes with lower limb amputation. Traumatic causes (excluding foot contusion) and bone diseases (excluding foot osteomyelitis) were reported in, respectively, 3% and 6% of people with diabetes and lower limb amputation, and were 5 and 13 times more frequent than in people without diabetes. We provide a first national estimate of lower limb amputation in France. We highlight its major impact on people with diabetes and its close relationship with peripheral arterial disease/neuropathy and renal complications in the national hospital discharge database. We do not suggest the exclusion of traumatic causes when studying the epidemiology of lower limb amputation related to diabetes, as diabetes may contribute to amputation even when the first cause appears to be traumatic.