First case report of pulmonary nocardiosis caused by Nocardia mexicana.
Nocardia species usually cause opportunistic infections, and the frequency of these infections is increasing owing to the growing population of immunocompromised hosts. However, Nocardia species may sometimes cause an infection disease in immunocompetent hosts. Nocardia mexicana infections are the least common and are very rare. Herein, we report the first case of a pulmonary infection with N. mexicana in a 61-year-old Japanese woman with a history of hyperlipidaemia and bronchiectasis and a 6-month history of non-productive hacking cough. A sample of bronchial lavage fluid obtained by bronchofiberscopy showed filamentous branching gram-positive rods and acid-fast filamentous branching rods, and a colony of suspected Nocardia was cultured. Based on 16S rRNA, gyrB,rpoB, secA1 and hsp65 gene sequence analyses and biochemical and physiological properties, the strain was identified as N. mexicana. The strain was resistant to the antimicrobial agents amoxicillin-clavulanic acid, clarithromycin, minocycline, gentamycin, tobramycin, ciprofloxacin and trimethoprim-sulfamethoxazole. The patient was treated with biapenem followed by intravenous amikacin and oral linezolid. Despite its rarity, the species require attention owing to the existence of multidrug-resistant strains.


Assessing a multilevel model of young children's oral health with national survey data.
To empirically test a multilevel conceptual model of children's oral health incorporating 22 domains of children's oral health across four levels: child, family, neighborhood and state. The 2003 National Survey of Children's Health, a module of the State and Local Area Integrated Telephone Survey conducted by the Centers for Disease Control and Prevention's National Center for Health Statistics, is a nationally representative telephone survey of caregivers of children. We examined child-, family-, neighborhood-, and state-level factors influencing parent's report of children's oral health using a multilevel logistic regression model, estimated for 26 736 children ages 1-5 years. Factors operating at all four levels were associated with the likelihood that parents rated their children's oral health as fair or poor, although most significant correlates are represented at the child or family level. Of 22 domains identified in our conceptual model, 15 domains contained factors significantly associated with young children's oral health. At the state level, access to fluoridated water was significantly associated with favorable oral health for children. Our results suggest that efforts to understand or improve children's oral health should consider a multilevel approach that goes beyond solely child-level factors.


Immunohistochemical localization of calcitonin gene-related peptide and substance P in the rat knee cartilage at birth.
Substance P (SP) and calcitonin gene-related peptide (CGRP) have been found in the perichondrium and within the cartilage canals. It is still unknown whether they exert a direct effect on chondrocytes during joint development. We processed 28 knees of newborn Wistar rats in 7 different fashions to perform histology and immunohistochemistry studies. Positive immunoreactivity against CGRP and SP was found in the inner aspect of the perichondrium in a close contact with chondrocytes. The presence of CGRP and SP indicates the presence of nerves fibers, and precedes the development of cartilage canals. Nerve fibers may play a role in the development of synovial joints before and during the presence of cartilage canals. The presence of CGRP and SP in the cartilage at birth may be involved in the early postnatal maturation of synovial joints. It remains to be determined whether autonomic innervation is later involved in age-related degenerative joint disease.


A four-gene operon in Bacillus cereus produces two rare spore-decorating sugars.
Bacterial glycan structures on cell surfaces are critical for cell-cell recognition and adhesion and in host-pathogen interactions. Accordingly, unraveling the sugar composition of bacterial cell surfaces can shed light on bacterial growth and pathogenesis. Here, we found that two rare sugars with a 3-C-methyl-6-deoxyhexose structure were linked to spore glycans in Bacillus cereus ATCC 14579 and ATCC 10876. Moreover, we identified a four-gene operon in B. cereus ATCC 14579 that encodes proteins with the following sequential enzyme activities as determined by mass spectrometry and one- and two-dimensional NMR methods: CTP:glucose-1-phosphate cytidylyltransferase, CDP-Glc 4,6-dehydratase, NADH-dependent SAM:C-methyltransferase, and NADPH-dependent CDP-3-C-methyl-6-deoxyhexose 4-reductase. The last enzyme predominantly yielded CDP-3-C-methyl-6-deoxygulose (CDP-cereose) and likely generated a 4-epimer CDP-3-C-methyl-6-deoxyallose (CDP-cillose). Some members of the B. cereus sensu lato group produce CDP-3-C-methyl-6-deoxy sugars for the formation of cereose-containing glycans on spores, whereas others such as Bacillus anthracis do not. Gene knockouts of the Bacillus C-methyltransferase and the 4-reductase confirmed their involvement in the formation of cereose-containing glycan on B. cereus spores. We also found that cereose represented 0.2-1% spore dry weight. Moreover, mutants lacking cereose germinated faster than the wild type, yet the mutants exhibited no changes in sporulation or spore resistance to heat. The findings reported here may provide new insights into the roles of the uncommon 3-C-methyl-6-deoxy sugars in cell-surface recognition and host-pathogen interactions of the genus Bacillus.


A CDC25 family protein phosphatase gates cargo recognition by the Vps26 retromer subunit.
We describe a regulatory mechanism that controls the activity of retromer, an evolutionarily conserved sorting device that orchestrates cargo export from the endosome. A spontaneously arising mutation that activates the yeast (Saccharomyces cerevisiae) CDC25 family phosphatase, Mih1, results in accelerated turnover of a subset of endocytosed plasma membrane proteins due to deficient sorting into a retromer-mediated recycling pathway. Mih1 directly modulates the phosphorylation state of the Vps26 retromer subunit; mutations engineered to mimic these states modulate the binding affinities of Vps26 for a retromer cargo, resulting in corresponding changes in cargo sorting at the endosome. The results suggest that a phosphorylation-based gating mechanism controls cargo selection by yeast retromer, and they establish a functional precedent for CDC25 protein phosphatases that lies outside of their canonical role in regulating cell cycle progression.


CT and DSA for evaluation of spontaneous intracerebral lobar bleedings.
This study retrospectively examined the extent to which computed tomography angiography (CTA) and digital subtraction angiography (DSA) can help identify the cause of lobar intracerebral bleeding. In the period from 2002 to 2020, data from patients who were >18 years at a university and an academic teaching hospital with lobar intracerebral bleeding were evaluated retrospectively. The CTA DSA data were reviewed separately by two neuroradiologists, and differences in opinion were resolved by consensus after discussion. A positive finding was defined as an underlying vascular etiology of lobar bleeding. The data of 412 patients were retrospectively investigated. DSA detected a macrovascular cause of bleeding in 125/412 patients (33%). In total, sixty patients had AVMs (15%), 30 patients with aneurysms (7%), 12 patients with vasculitis (3%), and 23 patients with dural fistulas (6%). The sensitivity, specificity, positive and negative predictive values, and accuracy of CTA compared with DSA were 93, 97, 100, and 97%. There were false-negative CTA readings for two AVMs and one dural fistula. The DSA is still the gold standard diagnostic modality for detecting macrovascular causes of ICH; however, most patients with lobar ICH can be investigated first with CTA, and the cause of bleeding can be found. Our results showed higher sensitivity and specificity than those of other CTA studies.


Development of a multi-channel 320 GHz interferometer for high density plasma measurement in Heliotron J.
We report the development of a new interferometer with two stable, high-power, 320 GHz solid-state sources in Heliotron J. A heterodyne Michelson interferometer optical scheme is employed. Two solid-state oscillators are utilized as sources with a fixed frequency at 320 GHz and frequency tunable of 312-324 GHz. Quasi-optical techniques are used for beam transmission. The beam is elongated in the vertical direction with two off-axis parabolic mirrors and injected into the plasma as a sheet beam for the multi-channel measurement (>5 ch.). Passing through the plasma, the beam is reflected at a retroreflector-array installed at the vacuum chamber wall. The retroreflector-array is a bunch of retroreflector structures, which can suppress the beam refraction caused by plasma without much space inside a vacuum chamber unlike a single retroreflector and can facilitate the system design. The source, detectors, and the retroreflector-array are tested to evaluate their basic performance on a tabletop experiment.


Molecular mechanism of transcriptional repression of gelsolin in human breast cancer cells.
Loss of gelsolin, a tumor suppressor, is one of the most frequently occurring molecular defects in breast cancers of diverse etiologies and across at least three animal species: human, mouse, and rat. Our previous analysis of breast cancer cells demonstrated that the deficiency is not due to mutation of the gelsolin gene, but instead to epigenetic factors, including decreased transcription of the gene. The study described herein provides the first functional characterization of the human gelsolin promoter and reveals a mechanistic basis for the reduced gelsolin transcription. In reporter gene assays, the gelsolin promoter was less active in low-gelsolin-expressing breast cancer cells. A cis-element mediating this reduced promoter activity was defined as a 27-bp sequence located approximately 135 bp upstream of the transcription start site. Gel shift and supershift assays and Southwestern blotting analysis indicated that activating transcription factor-1 (ATF-1) and a protein of approximately 100 kDa may have cancer cell-specific DNA-binding activity to the 27-bp gelsolin cis-element. Although the ATF-1 protein was highly expressed in both benign and tumorigenic breast cells, its DNA-binding activity was selectively abundant in the cancer cells and correlated inversely with the gelsolin mRNA level. Thus, our results suggest a role for ATF-1 in gelsolin promoter silencing in contrast to its transactivating effect on various other promoters.


Polypeptide fragments of horse cytochrome c activate a small subset of secondary B lymphocytes primed against the native protein.
Horse cytochrome c (cyt c) and two large, overlapping cyanogen bromide-cleaved fragments (1-80 and 66-104), together encompassing the entire length of the polypeptide chain, were examined for their abilities to stimulate into antibody production individual secondary B lymphocytes primed against the intact protein. T cell help was provided against the carrier protein, hemocyanin, to which cyt c and its peptides were conjugated by using glutaraldehyde. All the B cells activated by both of the fragments elicited antibodies that reacted with intact cyt c in enzyme-linked immunosorbent assay, whereas only a fraction of the antibodies elicited by the intact protein reacted with the peptides. However, in general, antibodies reactive with the polypeptide fragments, whether elicited by the intact protein or by the fragments, could not be effectively inhibited from binding plate-bound cyt c in enzyme-linked immunosorbent assay in the presence of soluble native cyt c. This indicates that these antibodies are specific for denatured forms of cyt c that apparently arise during the chemical coupling of cyt c to carrier molecules for immunization and/or during emulsification of the immunogen in adjuvant. Whereas, at most, 5% of the secondary B cells specific for native cyt c could be activated by the 1-80 fragment, even fewer were activated by the 66-104 fragment. Therefore, it is unlikely that smaller peptides which fail to assume native conformation would be effective. Antibodies elicited in vivo in a primary response to the 1-80 fragment also failed to bind native cyt c. These results suggest that linear peptides intended to mimic epitopes on globular proteins, and which have not been engineered to adopt native conformation, will not be very effective either as primary or as secondary vaccines for B cell activation.


Effects of cellulose derivative hydrocolloids on pasting, viscoelastic, and morphological characteristics of rice starch gel.
Effects of sodium carboxymethyl cellulose (CMC) and hydroxypropyl methyl cellulose (HPMC) on the pasting, viscoelastic, and morphological properties of rice starch gel were studied. The addition of CMC increased the peak and trough viscosities, while decreased the final and setback viscosities of rice starch. The peak and trough viscosities of rice starch gel were only little affected by the addition of HPMC. The dynamic viscoelastic result showed that the addition of CMC significantly increased the values of storage modulus (G') and loss modulus (G″), while reduced the value of tanδ as compared to the control sample. Only a small increase in values of G' and G″ was observed in the case of HPMC. The rice starch gel with CMC addition exhibited higher resistances to the stress and produced a stronger gel network. The creep recovery data were well fitted by a four-element Burger's model. Furthermore, the morphological characteristics were in agreement with the finding of rheological results. It was concluded that the addition of CMC and HPMC modified the rheology of rice starch gel in different ways and interacted under different models based on their molecular structures. Gluten-free foods such as rice cake are essential for people who suffer from celiac disease which is a digestive disorder caused by the consumption of grains containing gluten. The use of CMC and HPMC represents the most widespread approach used to mimic gluten in the manufacture of gluten-free breads based on rice starch, due to their structure-building and water-binding properties. Therefore, it is necessary and crucial to investigate the physical-chemical properties such as pasting and rheological properties of the rice starch with these hydrocolloids. In addition, a better understanding of the interactions of CMC and HPMC on the rice starch could provide additional tools for selection of gluten free recipes with improved rheological and textural properties.


Impact of work-related pain on physical therapists and occupational therapists.
Physical therapists and occupational therapists experience high rates of work-related pain. Although most therapists continue to work through this pain, it interferes with work and alters therapists' work habits. However, the effects on productivity, quality of patient care, and therapists' quality of life and long-term career plans are unknown. The purpose of this study was to determine the impact of working with work-related pain on physical therapists and occupational therapists. Multiple methods were used in this study. It was primarily a phenomenological study. A phenomenological approach was used to explore the meaning of work-related pain in therapists. Focus group interviews were used as the method of data collection. A questionnaire was used to supplement the qualitative analysis. Nineteen therapists participated in 4 focus groups ranging from 2 to 7 participants each. The participants noted substantial effects of work-related pain at work, at home, and in their career plans. All of the therapists were concerned about their potential clinical longevity. The professional culture complicated these effects by forcing therapists into a professional ideal. Work-related pain affects therapists in several personal and professional domains. It also may affect career plans. Strategies to reduce the risk of injury and physical loading of jobs are needed.


Survival of Campylobacter jejuni in water: effect of grazing by the freshwater crustacean Daphnia carinata (Cladocera).
Environmental studies of the human-pathogenic bacterium Campylobacter jejuni have focused on linking distributions with potential sources. However, in aquatic ecosystems, the abundance of C. jejuni may also be regulated by predation. We examine the potential for grazing by the freshwater planktonic crustacean Daphnia carinata to reduce the survival of C. jejuni. We use a system for measuring grazing and clearance rates of D. carinata on bacteria and demonstrate that D. carinata can graze C. jejuni cells at a rate of 7% individual(-1) h(-1) under simulated natural conditions in the presence of an algal food source. We show that passage of C. jejuni through the Daphnia gut and incorporation into fecal material effectively reduces survival of C. jejuni. This is the first evidence to suggest that grazing by planktonic organisms can reduce the abundance of C. jejuni in natural waters. Biomanipulation of planktonic food webs to enhance Daphnia densities offers potential for reducing microbial pathogen densities in drinking water reservoirs and recreational water bodies, thereby reducing the risk of contracting water-borne disease.


Acute Biventricular Interaction in Pediatric Patients Implanted with Continuous Flow and Pulsatile Flow LVAD: A Simulation Study.
Left ventricular assist devices (LVADs) are used to bridge pediatric patients till transplantation. However, the LVADs effects on right ventricular (RV) function are controversial. This work aims at studying the ventricular interdependency in the presence of continuous (c-) and pulsatile (p-) flow LVAD in pediatric patients using a lumped parameter model including the representation of the septum. Five pediatric patients' data were used to simulate patients' baseline. The effects on LV and RV functions, energetics, preloads and afterloads of different c-LVAD speeds, p-LVAD rate, p-LVAD systole duration, p-LVAD filling and ejection pressures were simulated. c-LVAD and p-LVAD unload the LV decreasing the LV external work and improving the LV ventriculo-arterial coupling and these effects are more evident increasing the c-LVAD speed and the p-LVAD rate. Continuous-LVAD and p-LVAD decrease the RV afterload, increase the RV ejection fraction and improve the RV ventriculo-arterial coupling. The changes in RV function are inversely proportional to the degree of the interventricular septum leftward shift that increased by increasing the LVAD contribution. The study of the interventricular interaction could lead to the development of a dedicated algorithm to optimize LVAD setting in pediatric population.


Effects of complete monocular deprivation in visuo-spatial memory.
Monocular deprivation has been associated with both specific deficits and enhancements in visual perception and processing. In this study, performance on a visuo-spatial memory task was compared in congenitally monocular individuals and sighted control individuals viewing monocularly (i.e., patched) and binocularly. The task required the individuals to view and memorize a series of target locations on two-dimensional matrices. Overall, congenitally monocular individuals performed worse than sighted individuals (with a specific deficit in simultaneously maintaining distinct spatial representations in memory), indicating that the lack of binocular visual experience affects the way visual information is represented in visuo-spatial memory. No difference was observed between the monocular and binocular viewing control groups, suggesting that early monocular deprivation affects the development of cortical mechanisms mediating visuo-spatial cognition.


Two new anticancer phenolic derivatives from leaves of Piper betle Linn.
In this study, phytochemical analyses of the chloroform extract of Piper betle L. var. haldia and maghai, Piperaceae, leaves led to the isolation of two new phenolic derivatives: 1-n-decanoyl hydroxy-benzoic acid/1-n-decanoyl phenol (H2) and 3-butylphenol (M1) on the basis of spectroscopic data 1D NMR (1H, 13C) and 2D NMR (1H - 1H COSY, HMBC) as well as ESI-MS, FT-IR and HR-ESI-MS analyses. Compounds H2 and M1 showed excellent antioxidant DPPH free radical scavenging activity with IC50 values of 10.66 μ/mL and 13.65 μg/mL compared to ascorbic acid as a standard antioxidant with an IC50 value of 2.52 μg/mL. Evaluation of cytotoxic activity against two human oral cancer cell lines (SCC-40 and SCC-29B) showed significant effect with GI50 values of 24.08 and 33.08 μg/mL for compound H2 and 35.03 and 47.06 μg/mL for compound M1, compared to Doxorubicin® as a standard cytotoxic drug with GI50 value of < 10 μg/mL.


Cu Nanoclusters-Encapsulated Liposomes: Toward Sensitive Liposomal Photoelectrochemical Immunoassay.
Herein we report the strategy of liposome-mediated Cu2+-induced exciton trapping upon CdS quantum dots (QDs) for amplified photoelectrochemical (PEC) bioanalysis application. Specifically, the Cu nanoclusters (NCs)-encapsulated liposomes were first fabricated and then processed with antibodies bound to their external surfaces. After the sandwich immunocomplexing, the confined liposomal labels were subjected to sequential lysis treatments for the release of Cu NCs and numerous Cu2+ ions, which were then directed to interact with the CdS QDs electrode. The interaction of Cu2+ ions with CdS QDs could generate CuxS and form the trapping sites to block the photocurrent generation. Since the photocurrent inhibition is closely related with the Cu NCs-loaded liposomal labels, a novel and general "signal-off" PEC immunoassay could thus be tailored with high sensitivity. Meanwhile, a complementary "signal-on" fluorescent detection could be accomplished by measuring the fluorescence intensity originated from the Cu NCs. This work features the first use of Cu NCs in PEC bioanalysis and also the first NCs-loaded liposomal PEC bioanalysis. More importantly, by using other specific ions/reagents-semiconductors interactions, this protocol could serve as a common basis for the general development of a new class of liposome-mediated PEC bioanalysis.


The effect of Lacto- and Bifidobacteria in monoculture on the vaginal microflora in norm and in cases of intravaginal staphylococcosis.
The influence of probiotic strains of Lactobacillus casei IMV B-7280, Lactobacillus acidophilus IMV B-7279, Bifidobacterium animalis VKL, Lactobacillus delbrueckii subsp. bulgaricus IMV B-7281 and Bifidobacterium animalis VKB, each strain separately, to the range of the urogenital tract microflora in physiological norm and in cases of experimental intravaginal staphylococcosis of mice induced by Staphylococcus aureus 8325-4. It was found that all these strains had different efficiency in Staphylococcus aureus 8325-4 growth suppression in the vagina of infected mice and affect the spectrum of microorganisms. Lactobacillus casei IMV B-7280 strain had effective antistaphylococcal effect and reduced the number of coliform bacteria and fungi in the vagina in cases of intravaginal staphylococcosis of mice. Lactobacillus casei IMV B-7280 strain is promising to create probiotic drugs effective in treating intravaginal staphylococcosis.


Changing practice patterns of Gamma Knife versus linear accelerator-based stereotactic radiosurgery for brain metastases in the US.
Single-fraction stereotactic radiosurgery (SRS) is a crucial component in the management of limited brain metastases from non-small cell lung cancer (NSCLC). Intracranial SRS has traditionally been delivered using a frame-based Gamma Knife (GK) platform, but stereotactic modifications to the linear accelerator (LINAC) have made an alternative approach possible. In the absence of definitive prospective trials comparing the efficacy and toxicities of treatment between the 2 techniques, nonclinical factors (such as technology accessibility, costs, and efficiency) may play a larger role in determining which radiosurgery system a facility may choose to install. To the authors' knowledge, this study is the first to investigate national patterns of GK SRS versus LINAC SRS use and to determine which factors may be associated with the adoption of these radiosurgery systems. The National Cancer Data Base was used to identify patients > 18 years old with NSCLC who were treated with single-fraction SRS to the brain between 2003 and 2011. Patients who received "SRS not otherwise specified" or who did not receive a radiotherapy dose within the range of 12-24 Gy were excluded to reduce the potential for misclassification. The chi-square test, t-test, and multivariable logistic regression analysis were used to compare potential demographic, clinicopathologic, and health care system predictors of GK versus LINAC SRS use, when appropriate. This study included 1780 patients, among whom 1371 (77.0%) received GK SRS and 409 (23.0%) underwent LINAC SRS. Over time, the proportion of patients undergoing LINAC SRS steadily increased, from 3.2% in 2003 to 30.8% in 2011 (p < 0.001). LINAC SRS was adopted more rapidly by community versus academic facilities (overall 29.2% vs 17.2%, p < 0.001). On multivariable analysis, 4 independent predictors of increased LINAC SRS use emerged, including year of diagnosis in 2008-2011 versus 2003-2007 (adjusted OR [AOR] 2.04, 95% CI 1.52-2.73, p < 0.001), community versus academic facility type (AOR 2.04, 95% CI 1.60-2.60, p < 0.001), non-West versus West geographic location (AOR 4.50, 95% CI 2.87-7.09, p < 0.001), and distance from cancer reporting facility of < 20 versus ≥ 20 miles (AOR 1.57, 95% CI 1.21-2.04, p = 0.001). GK remains the most commonly used single-fraction SRS modality for NSCLC brain metastases in the US. However, LINAC-based SRS has been rapidly disseminating in the past decade, especially in the community setting. Wide geographic variation persists in the distribution of GK and LINAC SRS cases. Further comparative effectiveness research will be needed to evaluate the impact of these shifts on SRS-related toxicities, local control, and survival, as well as treatment costs and efficiency.


Child abuse: is there a mandate for researchers to report?
During the past 20 years, states have increasingly expanded the lists of individuals who are obligated to report their suspicions of child abuse and neglect. These legal requirements are juxtaposed with ethical considerations in research and professional practice. The ethical issues include the obligation to maintain both confidentiality of information provided by human participants and the safety and protection of these participants. This article reviews the types of state child abuse reporting statutes and outlines the categories of mandated reporters. I develop a model of how individual researchers should approach deciding whether they are mandated reporters of child abuse and neglect.


The respiratory resistance sensitivity task: An automated method for quantifying respiratory interoception and metacognition.
The ability to sense, monitor, and control respiration - e.g., respiratory interoception (henceforth, respiroception) is a core homeostatic ability. Beyond the regulation of gas exchange, enhanced awareness of respiratory sensations is directly related to psychiatric symptoms such as panic and anxiety. Indeed, chronic breathlessness (dyspnea) is associated with a fourfold increase in the risk of developing depression and anxiety, and the regulation of the breath is a key aspect of many mindfulness-based approaches to the treatment of mental illness. Physiologically speaking, the ability to accurately monitor respiratory sensations is important for optimizing cardiorespiratory function during athletic exertion, and can be a key indicator of illness. Given the important role of respiroception in mental and physical health, it is unsurprising that there is increased interest in the quantification of respiratory psychophysiology across different perceptual and metacognitive levels of the psychological hierarchy. Compared to other more popular modalities of interoception, such as in the cardiac domain, there are relatively few methods available for measuring aspects of respiroception. Existing inspiratory loading tasks are difficult to administer and frequently require expensive medical equipment, or offer poor granularity in their quantification of respiratory-related perceptual ability. To facilitate the study of respiroception, we here present a new, fully automated and computer-controlled apparatus and psychophysiological method, which can flexibly and easily measure respiratory-related interoceptive sensitivity, bias and metacognition, in as little as 30 min of testing, using easy to make 3D printable parts.


Bioactivity of anacardic acid against colorado potato beetle (Leptinotarsa decemlineata) larvae.
Anacardic acid (2-hydroxy-6-alkylbenzoic acid) produced and secreted from glandular trichomes of zonal geranium (Pelargonium x hortorum; Geraniaceae family) provides resistance to small pests (aphids and spider mites). To assess the potential bioactivity of anacardic acid against larger insect pests and to determine if an alternate mode of application (ingestion rather than the topical application) could impart resistance to pests, the effects of anacardic acid consumption on the development of Colorado potato beetle larvae were tested. Analysis of dose-response curves indicated a significant effect on weight gain and mortality. Assessment of food preference (treated versus untreated) indicated larvae avoid food containing anacardic acid and have a lower feeding rate on food containing anacardic acid. On the basis of these results, it is suggested that anacardic acid, applied as a chemical spray or through bioengineering production in crop plants, may provide a new tool in the arsenal to minimize damage to plants caused by pests.


Development and characterization of optoelectronic circuit boards produced by two-photon polymerization using a polysiloxane containing acrylate functional groups.
Research into the integration of optical interconnects in printed circuit boards (PCBs) is rapidly gaining interest due to the increase in data transfer speeds now required along with the need for miniaturized devices with increased complexity and functionality. We present a method that involves embedding optoelectronic components in a polymeric material and fabricating optical waveguides in one step. A silanol-terminated polysiloxane cross-linked with an acryloxy functional silane is utilized as a matrix material into which the 3D optical waveguides are inscribed by two-photon-induced polymerization. A pulsed femtosecond laser is used to directly write optical waveguides into the material, forming an optical link between lasers and photodiodes that are directly mounted on a specially designed PCB. The boards produced were characterized by monitoring the transmitted photocurrent as well as temperature-dependent data transmission properties. Data rates exceeding 4 Gbit/s were achieved.


Expression of CD1 in the mouse thymus.
The CD1 antigens are a family of differentiation antigens found predominantly, but not exclusively, in the human thymus. Although three antigens (CD1a-c) are described by monoclonal antibodies, five genes (CD1A-E) are found in the human genome. The cloning of the mouse CD1 genes (Bradbury, A., Belt, K.T., Nery, T.M., Milstein, C. and Calabi, F., EMBO J. 1988. 7:3081) demonstrated the presence of homologues to human CD1D, but not to any of the other human CD1 genes. In this work we have examined the expression of mouse CD1D mRNA in the thymus and shown that it is predominantly cortical, as is the expression of the CD1 antigens in man. Somewhat surprisingly, we also find that most CD1D mRNA in the mouse thymus is unspliced. Despite this, we have also been able to show, using a polyclonal antiserum directed against a bacterial fusion protein, the existence of the expected protein product.


Collective equipoise, disappointment, and the therapeutic misconception: on the consequences of selection for clinical research.
Private information induces individuals to self-select as subjects into clinical research trials, and it induces researchers to select which trials they conduct. The authors show that selection can induce ex ante therapeutic misconception and ex post disappointment among research subjects, and it undermines the rationale of collective equipoise as an ethical basis for clinical trials. Selection provides a reason to make nontrivial payments to subjects, and it implies that researchers should not design experiments to maximize statistical power.


Polymer-additive extraction via pressurized fluids and organic solvents of variously cross-linked poly(methylmethacrylates).
Variously cross-linked poly(methylmethacrylates) (PMMAs) are synthesized with three additives incorporated at theoretically 1000 microg of the additive per gram of prepared polymer. The additives are Irganox 1010, Irganox 1076, and Irgafos 168. The in-house" synthesized polyacrylates are then subjected to supercritical fluid extraction (SFE) to determine if additive recovery is a function of percent cross-linking. Although considerable work in this regard has been performed with non-cross-linked polyolefins, the literature is lacking regarding polyacrylates. Some additive degradation apparently occurs during the synthesis, as judged by the increased complexity of the extract high-performance liquid chromatographic trace and the low percent recoveries observed especially for the Irganoxes. For low polymer cross-linking (1%), it appears that both PMMA synthetic reproducibility and readily observed polymer swelling during SFE are serious issues that adversely affect additive percent recovery and precision of results. Higher percent cross-linking yields more consistent analytical data than low percent cross-linking, even though the amount of additive extracted in all PMMA samples (regardless of cross-linking percentage) is essentially the same whether the extraction is via SFE or liquid-solid extraction with methylene chloride. Results for comparably cross-linked poly(ethylmethacrylate) and poly(butylmethacrylate) are similar to PMMA.


Acquisition of the polarity sensitive item renhe 'any' in Mandarin Chinese.
The present study investigated Mandarin-speaking children's acquisition of the polarity sensitive item renhe 'any' in Mandarin Chinese. Like its English counterpart any, renhe can be used as a negative polarity item (NPI), or as a free choice (FC) item, and both the distribution and interpretation of renhe are governed by the same syntactic and semantic constraints as English any. Using a Truth Value Judgment Task, the present study tested five-year-old Mandarin-speaking children's comprehension of FC renhe in sentences containing the modal word neng 'can', and tested children's comprehension of NPI renhe in sentences containing the temporal conjunction zai…zhiqian 'before'. Most children demonstrated knowledge of the interpretation of both FC renhe and NPI renhe despite a paucity of relevant adult input. Like adults, however, Mandarin-speaking children do not use renhe frequently in ordinary conversation, due to the availability of alternative colloquial expressions (wh-pronouns) that also convey children's intended meanings.


Multicentre comparison of quantitative PCR-based assays to detect SARS-CoV-2, Germany, March 2020.
Containment strategies and clinical management of coronavirus disease (COVID-19) patients during the current pandemic depend on reliable diagnostic PCR assays for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here, we compare 11 different RT-PCR test systems used in seven diagnostic laboratories in Germany in March 2020. While most assays performed well, we identified detection problems in a commonly used assay that may have resulted in false-negative test results during the first weeks of the pandemic.


Simulations of the dynamics of thermal undulations in lipid bilayers in the tensionless state and under stress.
The relaxation processes of height undulations and density fluctuations in a membrane have been studied by molecular dynamics simulations of a coarse grained amphiphilic bilayer model. We observe a double exponential decay in their time correlations, with relaxation rates in good quantitative agreement with the theory by Seifert and Langer [Europhys. Lett. 23, 71 (1993)]. Intermonolayer friction due to slippage between the two monolayers is shown to be the dominant dissipative mechanism at the high wave numbers, q>10 mum(-1), typically encountered in computer simulations. We briefly discuss the ramifications of the slow undulatory relaxation process for the calculation of bending rigidities from the static undulation structure factors. The relaxation rates are sensitive to the surface tension, and at high elongations an oscillatory contribution is observed in the time correlation of the undulations.


[Computed tomography (CT) utility for diagnosis and triage during COVID-19 pandemic].
The nasopharyngeal smear with PCR analysis is the first diagnostic test proposed to confirm infection with COVID-19 SARS-CoV-2. However, its usefulness in emergency centers is limited due to its imperfect sensitivity (56-83 %), limited availability and the time required to obtain results. For this reason, the chest CT-scan has been proposed as a rapid triage tool for diagnosis in these suspect Covid-19 patients. However, its specificity is limited, exposing to the risk of over-diagnosis, and further data are needed to confirm its usefulness, and to highlight the possible prognostic value of the CT, in detecting early lesions associated with poor outcome, indicating the need for admission to intensive care.


H2AX regulates meiotic telomere clustering.
The histone H2A variant H2AX is phosphorylated in response to DNA double-strand breaks originating from diverse origins, including dysfunctional telomeres. Here, we show that normal mitotic telomere maintenance does not require H2AX. Moreover, H2AX is dispensable for the chromosome fusions arising from either critically shortened or deprotected telomeres. However, H2AX has an essential role in controlling the proper topological distribution of telomeres during meiotic prophase I. Our results suggest that H2AX is a downstream effector of the ataxia telangiectasia-mutated kinase in controlling telomere movement during meiosis.


Human tumor growth in nude mice is associated with decreased plasma cysteine and homocysteine.
The methionine cycle and its metabolites homocysteine and cysteine serve several important functions in cellular metabolism. Abnormalities in metabolism of the methionine cycle have been associated with cancer. We determined plasma levels of methionine, homocysteine and cysteine in nude mice implanted with human cancer cell lines (MDA-MB-435 breast, PC-3 prostate, HT29 colon, BX-PC3 pancreas) over a prolonged period of tumor growth. The data were compared with correspondins values in nontumor-bearing controls. Nude mice were injected s.c. in the right flank with 10(6) cancer cells. Tumor growth was measured over time. Methionine was measured in plasma by HPLC. Cysteine and homocysteine were measured in plasma by recombinant enzyme assays and spectrophotometry to measure products. The concentrations of cysteine and homocysteine in plasma decreased significantly as a result of progression of breast, prostate and the pancreas tumor types implanted in the nude mice at least over a two-month period. Data for the colon tumors were nonsignificant for both cysteine and homocysteine. In the case of methionine, the decrease was significant only due to progression of the breast tumors, grown over a long time period, as compared to the mice without tumors control. The results suggest that sulphur amino acids may be plasma or serum biomarkers for cancer progression.


Comparing test-retest reliability of dynamic functional connectivity methods.
Due to the dynamic, condition-dependent nature of brain activity, interest in estimating rapid functional connectivity (FC) changes that occur during resting-state functional magnetic resonance imaging (rs-fMRI) has recently soared. However, studying dynamic FC is methodologically challenging, due to the low signal-to-noise ratio of the blood oxygen level dependent (BOLD) signal in fMRI and the massive number of data points generated during the analysis. Thus, it is important to establish methods and summary measures that maximize reliability and the utility of dynamic FC to provide insight into brain function. In this study, we investigated the reliability of dynamic FC summary measures derived using three commonly used estimation methods - sliding window (SW), tapered sliding window (TSW), and dynamic conditional correlations (DCC) methods. We applied each of these techniques to two publicly available rs-fMRI test-retest data sets - the Multi-Modal MRI Reproducibility Resource (Kirby Data) and the Human Connectome Project (HCP Data). The reliability of two categories of dynamic FC summary measures were assessed, specifically basic summary statistics of the dynamic correlations and summary measures derived from recurring whole-brain patterns of FC ("brain states"). The results provide evidence that dynamic correlations are reliably detected in both test-retest data sets, and the DCC method outperforms SW methods in terms of the reliability of summary statistics. However, across all estimation methods, reliability of the brain state-derived measures was low. Notably, the results also show that the DCC-derived dynamic correlation variances are significantly more reliable than those derived using the non-parametric estimation methods. This is important, as the fluctuations of dynamic FC (i.e., its variance) has a strong potential to provide summary measures that can be used to find meaningful individual differences in dynamic FC. We therefore conclude that utilizing the variance of the dynamic connectivity is an important component in any dynamic FC-derived summary measure.


Involvement of iron and iron-catalyzed free radical production in ethanol metabolism and toxicity.
Lipoperoxidation, a degradative process of membranous polyunsaturated fatty acids, has been suggested to represent an important mechanism in the pathogenesis of ethanol toxicity on the liver and possibly also on the brain. Catalysis by transition metals, especially iron, is involved in the biosynthesis of free radicals contributing to lipid peroxidation. Although the exact nature of the redox-active iron implicated in this catalysis is still unknown, it has been well established that lipid peroxidation can be prevented in vitro by iron chelators such as desferrioxamine. Deprivation of redox-active iron through desferrioxamine inhibits by about 50% the microsomal oxidation of ethanol in vitro and reduces very significantly in vivo the overall ethanol elimination rate in rats. Administration of desferrioxamine together with ethanol also reduces the ethanol-induced disturbances in the antioxidant defense mechanisms of the hepatocyte. It also reduces in mice both the severity of physical dependence on ethanol and lethality following the acute administration of a narcotic dose of ethanol. Chronic overloading of rats with iron results, on the opposite, in an increased rate of ethanol elimination, although alcohol dehydrogenase and catalase activities are reduced and cytochrome P-450 depleted in the liver of such iron-overloaded animals. The magnitude of the ethanol-induced increase in lipid peroxidation and decrease in the major membranous antioxidant, alpha-tocopherol, is exacerbated in iron-overloaded rats. Several disturbances of iron metabolism have been reported in human alcoholics. Their contribution to ethanol toxicity appears very likely in the case of hepatic siderosis associated with alcohol abuse. Ethanol could however disturb iron metabolism even in the absence of gross abnormalities of the total iron stores. It is suggested that ethanol intoxication could increase cellular redox-active iron, thus contributing to an enhanced steady-state concentration of reactive-free radicals. This oxidative stress would lead to lipoperoxidative damage and cellular injury.


Taxonomic Diversity Not Associated with Gross Karyotype Differentiation: The Case of Bighead Carps, Genus Hypophthalmichthys (Teleostei, Cypriniformes, Xenocyprididae).
The bighead carps of the genus Hypophthalmichthys (H. molitrix and H. nobilis) are important aquaculture species. They were subjected to extensive multidisciplinary research, but with cytogenetics confined to conventional protocols only. Here, we employed Giemsa-/C-/CMA3- stainings and chromosomal mapping of multigene families and telomeric repeats. Both species shared (i) a diploid chromosome number 2n = 48 and the karyotype structure, (ii) low amount of constitutive heterochromatin, (iii) the absence of interstitial telomeric sites (ITSs), (iv) a single pair of 5S rDNA loci adjacent to one major rDNA cluster, and (v) a single pair of co-localized U1/U2 snDNA tandem repeats. Both species, on the other hand, differed in (i) the presence/absence of remarkable interstitial block of constitutive heterochromatin on the largest acrocentric pair 11 and (ii) the number of major (CMA3-positive) rDNA sites. Additionally, we applied here, for the first time, the conventional cytogenetics in H. harmandi, a species considered extinct in the wild and/or extensively cross-hybridized with H. molitrix. Its 2n and karyotype description match those found in the previous two species, while silver staining showed differences in distribution of major rDNA. The bighead carps thus represent another case of taxonomic diversity not associated with gross karyotype differentiation, where 2n and karyotype structure cannot help in distinguishing between genomes of closely related species. On the other hand, we demonstrated that two cytogenetic characters (distribution of constitutive heterochromatin and major rDNA) may be useful for diagnosis of pure species. The universality of these markers must be further verified by analyzing other pure populations of bighead carps.


Visible-Light-Enabled Decarboxylative Sulfonylation of Cinnamic Acids with Sulfonylhydrazides under Transition-Metal-Free Conditions.
Decarboxylative cross-coupling reactions of cinnamic acids with sulfonylhydrazides were explored using oxygen as the sole terminal oxidant, realizing a conceptually novel technology for vinyl sulfone synthesis under the synergistic interactions of visible light irradiation, organic dye-type photocatalyst eosin Y, KI, and Cs2CO3 at room temperature.


Recovering a repressed memory, and representational shift in an adolescent.
This case report focuses on the disappearance of a fixed pictorial iconic representation and transformation to symbolic (word) representation following the recovery of a repressed memory in a twelve-and-a-half-year-old after the first eleven months of psychoanalysis. There is a substantial body of psychoanalytic literature on the importance of language, naming or articulation of experiences associated with transformation of psychic structure (Fenichel, 1941; Glover, 1955; Kris, 1956a, 1956b; Werner and Kaplan, 1963; Schafer, 1976, 1978a, 1978b, 1980; Shapiro, 1979; Spence, 1982; Stern, 1989) and a relatively autonomous literature on the communicative representational power of children's play or visual portrayals (Piaget, 1962; A. Freud, 1947; Klein, 1964; Axeline, 1947; Esman, 1983; Neubauer et al., 1987; Krall, 1989). To our knowledge, there is no report of the structural effect of the recovery of a repressed traumatic experience, in this case, with subsequent parental confirmation of the traumatic event.


Assessment of initial SARS-CoV-2 seroprevalence in the most affected districts in the municipality of São Paulo, Brazil.
São Paulo city has been one of the regions most affected by the COVID-19 pandemic in Brazil. Frequent asymptomatic and oligosymptomatic infections and poor access to diagnostic tests make serosurveys crucial to monitor the magnitude of the epidemic and to inform public health policies, such as vaccination plans. To estimate, early in the epidemic, the seroprevalence of antibodies to SARS-CoV-2 in adults living in the six most affected districts in São Paulo city, and to assess potential associated risk factors. This was a cross-sectional population-based survey of 1,152 households randomly selected from 72 census tracts. During the period May 4-12, 2020, 463 participants completed a questionnaire on sociodemographic characteristics and history of symptoms in the past two weeks, and provided a blood sample. Prevalence of SARS-CoV-2 antibodies was the outcome of interest and was estimated based on results of two immunoassays, Maglumi SARS-CoV-2 chemiluminescence assay Immunoglobulin (Ig) M (IgM) and IgG, and Roche electrochemiluminescence assay total Ig. Serum samples reactive to either assay were considered positive. Weighted overall seroprevalence was 6% (95%CI 3.9-8.3%). No association was observed between seropositivity and sex, age group or education level. Participants who reported black and brown skin color showed a 2.7 fold higher prevalence than people with white skin (p = 0.007). Among the 30 seropositive individuals, 14 (46.6%) reported no COVID-19 compatible symptoms in the past two weeks. This study represents the first assessment of SARS-CoV-2 seroprevalence in the city of São Paulo and 6% is the baseline estimate of a series of population-based seroprevalence surveys. Serological screening using sound serological assays is the key tool to monitoring temporal and geographic changes in the spread of the virus through an important epicenter of the COVID-19 pandemic in Brazil. Ultimately, it may inform prevention and control efforts.


Functional characterization of lysophosphatidic acid receptor 1 mutants identified in rat cancer tissues.
Lysophosphatidic acid (LPA), an extracellular lipid mediator, exerts various cellular effects through activation of LPA receptors, LPA1-LPA6, in many types of cells including cancer cells. We recently found several missense mutations of Lpar1 in rat cancer tissues. One of these mutations is located at the extracellular tip of the seventh transmembrane domain of LPA1, and another three mutations are found within the NPXXY motif in the seventh transmembrane domain. These mutants are designated F295S LPA1 and P308S, I310T, and Y311H LPA1, respectively. Here, we examined the functions of these LPA1 mutants. Compared with wild-type (WT) LPA1, F295S, P308S, and I310T LPA1 showed decreased maximal responses in inhibition of cAMP formation, Ca2+ mobilization, and cytoskeletal changes. Y311H LPA1 failed to show LPA-induced cellular responses. However, these LPA1 mutants were internalized in response to LPA exposure. Finally, while WT and F295S LPA1 showed a similar, broad distribution throughout the cell, P308S, I310T, and Y311H LPA1 displayed a restricted cellular distribution and co-localized with the endoplasmic reticulum. These data suggest that the LPA1 mutants perturb LPA signaling in cancer tissues.


Understanding Health Behavior Technology Engagement: Pathway to Measuring Digital Behavior Change Interventions.
Researchers and practitioners of digital behavior change interventions (DBCI) use varying and, often, incongruent definitions of the term "engagement," thus leading to a lack of precision in DBCI measurement and evaluation. The objective of this paper is to propose discrete definitions for various types of user engagement and to explain why precision in the measurement of these engagement types is integral to ensuring the intervention is effective for health behavior modulation. Additionally, this paper presents a framework and practical steps for how engagement can be measured in practice and used to inform DBCI design and evaluation. The key purpose of a DBCI is to influence change in a target health behavior of a user, which may ultimately improve a health outcome. Using available literature and practice-based knowledge of DBCI, the framework conceptualizes two primary categories of engagement that must be measured in DBCI. The categories are health behavior engagement, referred to as "Big E," and DBCI engagement, referred to as "Little e." DBCI engagement is further bifurcated into two subclasses: (1) user interactions with features of the intervention designed to encourage frequency of use (ie, simple login, games, and social interactions) and make the user experience appealing, and (2) user interactions with behavior change intervention components (ie, behavior change techniques), which influence determinants of health behavior and subsequently influence health behavior. Achievement of Big E in an intervention delivered via digital means is contingent upon Little e. If users do not interact with DBCI features and enjoy the user experience, exposure to behavior change intervention components will be limited and less likely to influence the behavioral determinants that lead to health behavior engagement (Big E). Big E is also dependent upon the quality and relevance of the behavior change intervention components within the solution. Therefore, the combination of user interactions and behavior change intervention components creates Little e, which is, in turn, designed to improve Big E. The proposed framework includes a model to support measurement of DBCI that describes categories of engagement and details how features of Little e produce Big E. This framework can be applied to DBCI to support various health behaviors and outcomes and can be utilized to identify gaps in intervention efficacy and effectiveness.


Personal experience with tympanoplasty in children.
An analysis is presented of a series of 434 operations in chronic otitis media in children taking into account the extent of the lesion, the type of operation, the early and late functional and morphological results. In 18% of cases a radical operation was performed, in 21% atticotomy or other conservative operations, and in 61% open or closed tympanoplasty. Because of dynamic character of the cholesteatomatous process in childhood, the creation of a "safe ear", i.e. free of recurrences of cholesteatoma, is difficult by means of closed tympanoplasty operations.


Photobiomodulation of Cytochrome c Oxidase by Chronic Transcranial Laser in Young and Aged Brains.
In cellular bioenergetics, cytochrome c oxidase (CCO) is the enzyme responsible for oxygen consumption in the mitochondrial electron transport chain, which drives oxidative phosphorylation for adenosine triphosphate (ATP) production. CCO is also the major intracellular acceptor of photons in the light wavelengths used for photobiomodulation (PBM). Brain function is critically dependent on oxygen consumption by CCO for ATP production. Therefore, our objectives were (1) to conduct the first detailed brain mapping study of the effects of PBM on regional CCO activity, and (2) to compare the chronic effects of PBM on young and aged brains. Specifically, we used quantitative CCO histochemistry to map the differences in CCO activity of brain regions in healthy young (4 months old) and aged (20 months old) rats from control groups with sham stimulation and from treated groups with 58 consecutive days of transcranial laser PBM (810 nm wavelength and 100 mW power). We found that aging predominantly decreased regional brain CCO activity and systems-level functional connectivity, while the chronic laser stimulation predominantly reversed these age-related effects. We concluded that chronic PBM modified the effects of aging by causing the CCO activity on brain regions in laser-treated aged rats to reach levels similar to those found in young rats. Given the crucial role of CCO in bioenergetics, PBM may be used to augment brain and behavioral functions of older individuals by improving oxidative energy metabolism.


Significant Change in Marine Plankton Structure and Carbon Production After the Addition of River Water in a Mesocosm Experiment.
Rivers are known to be major contributors to eutrophication in marine coastal waters, but little is known on the short-term impact of freshwater surges on the structure and functioning of the marine plankton community. The effect of adding river water, reducing the salinity by 15 and 30%, on an autumn plankton community in a Mediterranean coastal lagoon (Thau Lagoon, France) was determined during a 6-day mesocosm experiment. Adding river water brought not only nutrients but also chlorophyceans that did not survive in the brackish mesocosm waters. The addition of water led to initial increases (days 1-2) in bacterial production as well as increases in the abundances of bacterioplankton and picoeukaryotes. After day 3, the increases were more significant for diatoms and dinoflagellates that were already present in the Thau Lagoon water (mainly Pseudo-nitzschia spp. group delicatissima and Prorocentrum triestinum) and other larger organisms (tintinnids, rotifers). At the same time, the abundances of bacterioplankton, cyanobacteria, and picoeukaryote fell, some nutrients (NH4+, SiO43-) returned to pre-input levels, and the plankton structure moved from a trophic food web based on secondary production to the accumulation of primary producers in the mesocosms with added river water. Our results also show that, after freshwater inputs, there is rapid emergence of plankton species that are potentially harmful to living organisms. This suggests that flash flood events may lead to sanitary issues, other than pathogens, in exploited marine areas.


Human T-cell leukemia/lymphoma viruses. Life cycle, pathogenicity, epidemiology, and diagnosis.
Human T-cell leukemia/lymphoma virus type I (HTLV-I) was discovered in 1980, and it subsequently was found to be the cause of adult T-cell leukemia/lymphoma. A progressive neurologic disease known as tropical spastic paraparesis, or HTLV-I-associated myelopathy, has also been linked to infection with HTLV-I. A related virus, HTLV type II (HTLV-II), has been isolated from patients with hairy-cell leukemia, but it has not been proved to be the cause of any disease. In late 1988, US blood banks began screening all blood donations for antibodies to HTLV-I/II. This program has resulted in the identification of many unexpectedly seropositive blood donors and provided much information about the prevalence of HTLV-I/II in the United States. In this article, I review the replication of these agents, as well as their pathogenesis, diagnosis, and mechanisms of spread.


Immunization of networks with limited knowledge and temporary immunity.
Modern view of network resilience and epidemic spreading has been shaped by percolation tools from statistical physics, where nodes and edges are removed or immunized randomly from a large-scale network. In this paper, we produce a theoretical framework for studying targeted immunization in networks, where only n nodes can be observed at a time with the most connected one among them being immunized and the immunity it has acquired may be lost subject to a decay probability ρ. We examine analytically the percolation properties as well as scaling laws, which uncover distinctive characters for Erdős-Rényi and power-law networks in the two dimensions of n and ρ. We study both the case of a fixed immunity loss rate as well as an asymptotic total loss scenario, paving the way to further understand temporary immunity in complex percolation processes with limited knowledge.


Cutaneous immunopathology: recent observations.
Immunofluorescent studies are currently being done on patients with pemphigus, pemphigoid, dermatitis, lupus erythematosus and its variants, the cutaneous prophyrias, scarring alopecia, erosive mouth lesions, light-sensitive disorders, and cutaneous vasculitis. In this paper I shall review some of the recent advances in immunopathology and report the results that have been obtained in our laboratory.


Pharmacophore feature-based virtual screening for finding potent GSK-3 inhibitors using molecular docking and dynamics simulations.
Glycogen synthase kinase-3 (GSK-3) is a multitasking serine/threonine protein kinase, which is associated with the pathophysiology of several diseases such as diabetes, cancer, psychiatric and neurodegenerative diseases. Tideglusib is a potent, selective, and irreversible GSK-3 inhibitor that has been investigated in phase II clinical trials for the treatment of progressive supranuclear palsy and Alzheimer's disease. In the present study, we performed pharmacophore feature-based virtual screening for identifying potent targetspecific GSK-3 inhibitors. We found 64 compounds that show better GSK-3 binding potentials compared with those of Tideglusib. We further validated the obtained binding potentials by performing 20-ns molecular dynamics simulations for GSK-3 complexed with Tideglusib and with the best compound found via virtual screening in this study. Several interesting molecular-level interactions were identified, including a covalent interaction with Cys199 residue at the entrance of the GSK-3 active site. These findings are expected to play a crucial role in the binding of target-specific GSK-3 inhibitors.


The Mathematics of Psychotherapy: A Nonlinear Model of Change Dynamics.
Psychotherapy is a dynamic process produced by a complex system of interacting variables. Even though there are qualitative models of such systems the link between structure and function, between network and network dynamics is still missing. The aim of this study is to realize these links. The proposed model is composed of five state variables (P: problem severity, S: success and therapeutic progress, M: motivation to change, E: emotions, I: insight and new perspectives) interconnected by 16 functions. The shape of each function is modified by four parameters (a: capability to form a trustful working alliance, c: mentalization and emotion regulation, r: behavioral resources and skills, m: self-efficacy and reward expectation). Psychologically, the parameters play the role of competencies or traits, which translate into the concept of control parameters in synergetics. The qualitative model was transferred into five coupled, deterministic, nonlinear difference equations generating the dynamics of each variable as a function of other variables. The mathematical model is able to reproduce important features of psychotherapy processes. Examples of parameter-dependent bifurcation diagrams are given. Beyond the illustrated similarities between simulated and empirical dynamics, the model has to be further developed, systematically tested by simulated experiments, and compared to empirical data.


Assuring public health professionals are prepared for the future: the UAB public health integrated core curriculum.
In response to calls to improve public health education and our own desire to provide a more relevant educational experience to our Master of Public Health students, the University of Alabama at Birmingham (UAB) School of Public Health designed, developed, and instituted a fully integrated public health core curriculum in the fall of 2001. This curriculum combines content from discipline-specific courses in biostatistics, environmental health, epidemiology, health administration, and the social and behavioral sciences, and delivers it in a 15 credit hour, team-taught course designed in modules covering such topics as tobacco, infectious diseases, and emergency preparedness. Weekly skills-building sessions increase student competence in data analysis and interpretation, communication, ethical decision-making, community-based interventions, and policy and program planning. Evaluations affirm that the integrated core is functioning as intended: as a means to provide critical content in the core disciplines in their applied context. As public health education continues to be debated, the UAB public health integrated core curriculum can serve as one model for providing quality instruction that is highly relevant to professional practice.


Outcome Expectations for Exercise and Decisional Balance Questionnaires Predict Adherence and Efficacy of Exercise Programs in Dialysis Patients.
The purpose of this study was to define if Outcomes Expectations for Exercise (OEE) and Decisional Balance (DB) scales predict adherence to guided exercise programs and associate with the improvement in physical performance in the dialysis population. Participants (n = 40; age 63.6 ± 12.5 years) completed OEE and DB questionnaires before randomization to the experimental group (n = 20) and control group (n = 20) of a two-phased exercise program-the experimental group received eight weeks of supervised functional exercise and exercise counseling (1st phase) before commencing eight weeks of home-based exercise on non-dialysis days (2nd phase). Both groups performed intradialytic cycling on dialysis days during both study phases. Patients with above-median OEE and DB scores (>3.15 and >1.3, respectively) expressed significantly better adherence to intradialytic cycling (89% vs. 76%, 89% vs. 77%, respectively, p < 0.05). Experimental group patients with an above-median OEE (but not DB) score had significantly better adherence to supervised and home-based functional exercise (93% vs. 81% and 85% vs. 60%, respectively, p < 0.05). Baseline DB score predicted the final result in the hand-grip test and 6-min walk test. Low OEE and, to a lesser degree, low DB questionnaire scores associate with inferior adherence to dialysis bundled and home-based exercise programs and may help define patient subsets in need of intensified motivational input by exercise caregivers.


Outcomes of fractionated CyberKnife radiosurgery in patients with choroidal malignant melanoma.
The aim of this study was to evaluate local tumor control and complication development rates of fractionated CyberKnife radiosurgery (CRS) in patients with choroidal melanoma. A total of 29 patients with choroidal melanoma were treated with fractionated CRS at Ankara Oncology Research and Training Hospital, Department of Radiotherapy between May 2009 and December 2013. Patients were treated with CRS if the initial height of the choroidal melanoma was ≥ 6 mm, or juxtapapillary and/or juxtamacular tumors with a height of >2.5 mm. Ophthalmic examinations were performed at baseline and at months 3, 6, 9 and 15 after radiotherapy. Assessment of visual acuity and measurement of tumor base dimension and height using A-scan and B-scan echography were done at each visit. The mean age was 56 (27-75) years. Tumor was located on choroid in 23 and on ciliochoroid in 6 patients. 86.2% of all melanomas were classified as medium sized and 23.8% as large sized. A median total dose of 5000 cGy was applied. Median tumor height decreased from 7.5 mm at baseline to 4.4 mm at the last follow-up visit (p < 0.001). Median visual acuity decreased from 0.4 at baseline to hand motion (p < 0.001). One patient had been lost to the metastatic disease and one patient had been treated with enucleation due to recurrent tumor growth. CRS is an effective and reliable local treatment modality in uveal melanoma.


Non-invasive estimation of split renal function from routine 68Ga-SSR-PET/CT scans.
Patients with impaired kidney function are at elevated risk for nephrotoxicity and hematotoxicity from peptide receptor radionuclide therapy (PPRT) for advanced neuroendocrine tumors. Somatostatin receptor (SSR)-PET/CT imaging is the method of choice to identify sufficient SSR expression as a prerequisite for PRRT. Therefore, our study aimed to explore whether split renal function could be evaluated using imaging data from routine SSR-PET/CT prior to PRRT. In total, 25 consecutive patients who underwent SSR-PET/CT (Siemens Biograph mCT®) before PRRT between June 2019 and December 2020 were enrolled in this retrospective study. PET acquisition in the caudocranial direction started at 20 ± 0.5 min after an i.v. injection of 173 ± 20 MBq [68Ga]Ga-ha DOTATATE, and the kidneys were scanned at 32 ± 0.5 min p.i. The renal parenchyma was segmented semi-automatically using an SUV-based isocontour (SUV between 5 and 15). Multiple parameters including SUVmean of renal parenchyma and blood pool, as well as parenchyma volume, were extracted, and accumulation index (ACI: renal parenchyma volume/SUVmean) and total kidney accumulation (TKA: SUVmean x renal parenchyma volume) were calculated. All data were correlated with the reference standard tubular extraction rate (TER-MAG) from [99mTc]Tc-MAG3 scintigraphy and glomerular filtration rate (GFRCDK - EPI). SUVmean of the parenchymal tracer retention showed a negative correlation with TERMAG (r: -0.519, p < 0.001) and GFRCDK - EPI (r: -0.555, p < 0.001) at 32 min p.i. The herein-introduced ACI revealed a significant correlation (p < 0.05) with the total tubular function (r: 0.482), glomerular renal function (r: 0.461), split renal function (r: 0.916), and absolute single-sided renal function (r: 0.549). The mean difference between the split renal function determined by renal scintigraphy and ACI was 1.8 ± 4.2 % points. This pilot study indicates that static [68Ga]Ga-ha DOTATATE PET-scans at 32 min p.i. may be used to estimate both split renal function and absolute renal function using the herein proposed "Accumulation Index" (ACI).


Daily interactions in the parent-adult child tie: Links between children's problems and parents' diurnal cortisol rhythms.
Studies have established that grown children's problems affect parental well-being, but a dearth of research has addressed daily interactions and biological systems that may underlie these associations. This study examined whether parents have different types of daily interactions with adult children who have problems and whether those interactions are associated with variations in parents' diurnal cortisol rhythms. Middle-aged parents (n=197) reported their interactions with adult children for seven consecutive days and provided saliva, analyzed for cortisol, three times a day (wake, 30 min after wake, bedtime) for four of those days. Parents were more likely to report negative encounters but not less likely to report positive interactions or contact with adult children who suffered from problems. Interactions with adult children who had physical-emotional problems had more immediate same day associations with cortisol whereas interactions with adult children who had lifestyle-behavioral problems had more delayed, or next day associations with cortisol. Daily interactions and their associations with the hypothalamic-pituitary-adrenal-axis may be important mechanisms by which adult children with problems negatively affect parental well-being.


Cell Block and Its Impact in the Diagnosis of Jaw Lesions over Fine Needle Aspiration Cytology.
To determine the role and efficacy of fine needle aspiration cytology (FNAC) and cell block in diagnosis of jaw lesions and compare the agreement between FNAC and cell block to predict the diagnosis. The sample comprised 51 cases, including 12 odontogenic keratocysts (OKCs), 8 ameloblastomas, 22 radicular cysts, 7 dentigerous cysts, and 1 each of intraosseous mucoepidermoid carcinoma (MEC) and adenomatoid odontogenic tumor (AOT). FNAC samples remaining after hematoxylin and eosin (H&E)-stained cytosmear diagnosis were centrifuged at 3,000 rpm for 10 min. The supernatant was discarded and sediment mixed with 2-3 mL alcohol and filtered. To this, 10% formalin was added, filtered, taken for routine processing, and stained with H&E. The result of FNAC smear and cell block was compared with histopathological diagnosis. On cytological examination of the smears, 7 OKCs and 22 radicular cysts were diagnosed, whereas ameloblastomas, AOT, intraosseous MEC, and dentigerous cysts were not. This gave an agreement of 56.8% with the biopsy reports. Cell block sections stained with H&E of 12 OKCs, 22 radicular cysts, 1 MEC, and 3 cases of ameloblastoma offered a diagnosis in accordance with the biopsies giving an agreement of 74.5%, while dentigerous cyst and AOT failed to do so. In comparison with FNAC, additionally 5 cases of OKC and 1 of MEC could be detected, and in ameloblastoma, out of 8 cases, only 3 yielded a concordant diagnosis through the cell block technique. In comparison with FNAC, the architectural pattern and the morphology of the cells were better preserved by the cell block technique. This substantiates that cell block could be used as an ancillary technique to aid in definitive diagnosis of head and neck swellings.


[Perinatal outcome of multiple pregnancies in maternity wards in Knin and Livno in 1990-2002].
The aim of this study was to examine perinatal outcome of twin pregnancies in maternity wards in Livno and Knin. The perinatal outcome in these two maternity wards was examined retrospectively during the period 1990-2002. The incidence of twin births, the month with the highest incidence of twin births, the age and parity of the women with twins and their gestational age were examined. Also, we compared the perinatal outcome of twins with singletons, distribution according to sex, lie and presentation at birth. During 13 years 10,856 newborns were delivered, and 127 (1.2%) of them were twins. The incidence of twins in maternity wards in Knin and Livno during the war and after the war was not significantly different (p = 0.89). The month with the highest incidence of twin births was May (14.8%). The avarage age of women with twins was 28.9 +/- 9.7. Twins were born mostly by multiparas (2-4 deliveries). 94 (74%) twins were born on term and 33 (26%) twins before term. 74 newborns (7% per hundred) from singletons and 11 (43% per hundred) from twins died during perinatal period. Twins were delivered by cesarean section (27%) three times more often than singletons (8%). Hypertension in twin pregnancies (7%) was twice as frequent as in singletons (4%). 132 (51.6%) male and 122 (48.4%) female newborns were born. The distribution according to sex was: 58 pairs "male-females", 37 "male-male" and 32 pairs "female-female". The distribution according to presentation at birth was: 49% "cephalic-cephalic", 29% "cephalic-breech", 12% "cephalic-transverse", 5% "breech-breech" and all other combinations got 5%. In conclusion, our results during the war and after the war were not different from other centers and studies thanks to good antenatal care and selection of twin pregnancies for transportation on time to the center with higher level of health care.


Expandable metallic stents in benign tracheobronchial obstruction.
Expandable metallic stents offer advantages over previously available techniques for treating benign tracheobronchial stenosis or obstruction. Endoluminal stent placement offers a rapid and effective means of opening up narrowed airways, and results in excellent relief of symptoms and improvement in pulmonary function. Because they are delivered in a nonexpanded state using flexible over-wire systems, they can be placed using a flexible bronchoscope and can be located in second-order bronchial branches. Metallic stents have been used to treat benign airway obstruction caused by anastomotic narrowing after lung transplantation, infection, congenital lesions, tracheobronchial malacia, inflammatory conditions including relapsing polychondritis, Wegener granulomatosis, and acquired immunodeficiency syndrome, and external compression from benign mediastinal masses or fibrosis. The stents become epithelialized, which prevents migration and permits ciliary activity to continue. Significant complications can occur, including airway inflammation, stent migration, airway erosion, and stent fracture and collapse, but more serious complications are uncommon. Computed tomography is essential in imaging patients being considered for stent placement, as it allows 1) accurate representation of airway anatomy in three dimensions. 2) measurement of airway diameter, 3) evaluation of airway anatomy distal to a narrowed segment and invisible to bronchoscopy, 4) demonstration of dynamic changes in airway morphologic features during forced exhalation in patients with airway malacia, and 5) demonstration of focal or diffuse air trapping in lung peripheral to the abnormal airway. In patients who have had stent placement, computed tomography is valuable in assessing airway morphologic features and dynamics distal to the stent, and can be valuable in assessing stent dysfunction.


Clinical utility of haptoglobin in combination with CEA, NSE and CYFRA21-1 for diagnosis of lung cancer.
To investigate the clinical value in lung cancer of a combination of four serum tumor markers, haptoglobin (Hp), carcinoembryonic antigen (CEA), neuron specific enolase (NSE) as well as the cytokeratin 19 fragment (CYFRA21-1). Serum Hp (with immune-turbidimetric method), CEA, NSE, CYFRA21-1 (with chemiluminescence method) level were assessed in 193 patients with lung cancer, 87 patients with benign lung disease and 150 healthy controls. Differences of expression were compared among groups, and joint effects of these tumor markers for the diagnosis of lung cancer were analyzed. Serum tumor marker levels in patients with lung cancer were obviously higher than those with benign lung disease and normal controls (p<0.01). The sensitivities of Hp, CEA, NSE and CYFRA21-1 were 43.5%, 40.9%, 23.3% and 41.5%, with specificities of 90.7%, 99.2%, 97.9% and 97.9%. Four tumor markers combined together could produce a positive detection rate of 85.0%, significantly higher than that of any single test. With squamous carcinomas, the positive detection rates with Hp and CYFRA21-1 were higher than that of other markers. In the adenocarcinoma case , the positive detection rate of CEA was higher than that of other markers. For small cell carcinomas, the positive detection rate of NSE was highest. The area under receiver operating characteristic curve (AUCROC) of Hp in squamous carcinoma (0.805) was higher than in adenocarcinoma (0.664) and small cell carcinoma (0.665). Hp can be used as a new serum tumor marker for lung cancer. Combination detection of Hp, CEA, NSE and CYFRA21-1 could significantly improve the sensitivity and specificity in diagnosis of lung cancer, and could be useful for pathological typing.


Survival in patients with primary liver cancer, gallbladder and extrahepatic biliary tract cancer and pancreatic cancer in Europe 1999-2007: Results of EUROCARE-5.
The EUROCARE study collects and analyses survival data from population-based cancer registries (CRs) in Europe in order to provide data on between-country differences in survival and time trends in survival. This study analyses data on liver cancer, gallbladder and extrahepatic biliary tract cancers ("biliary tract cancers"), and pancreatic cancer diagnosed in 2000-2007 from 88 CRs in 29 countries. Relative survival (RS) was estimated overall, by region, sex, age and period of diagnosis using the complete approach. Time trends in 5-year RS over 1999-2007 were also analysed using the period approach. The prognosis of the studied cancers was poor. Age-standardised 5-year RS was 12% for liver cancer, 17% for biliary tract cancers and 7% for pancreatic cancer. There were some between-country differences in survival. In general, RS was low in Eastern Europe and high in Central and Southern Europe. For all sites, 5-year RS was similar in men and women and decreased with advancing age. No substantial changes in survival were reported for pancreatic cancer over the period 1999-2007. On average, there was a crude increase in 5-year RS of 3 percentage points between the periods 1999-2001 and 2005-2007 for liver cancer and biliary tract cancers. The major changes in imaging techniques over the study period for the diagnosis of the three studied cancers did not result in an improvement in the prognosis of these cancers. In the near future, new innovative treatments might be the best way to improve the prognosis in these cancers.


Advanced endoscopic imaging for diagnosis of inflammatory bowel diseases: Present and future perspectives.
Crohn's disease and ulcerative colitis are chronic inflammatory bowel diseases (IBD) causing severe damage of the luminal gastrointestinal tract. Differential diagnosis between both disease entities is sometimes awkward requiring a multifactorial pathway, including clinical and laboratory data, radiological findings, histopathology and endoscopy. Apart from disease diagnosis, endoscopy in IBD plays a major role in prediction of disease severity and extent (i.e. mucosal healing) for tailored patient management and for screening of colitis-associated cancer and its precursor lesions. In this state-of-the-art review, we focus on current applications of endoscopy for diagnosis and surveillance of IBD. Moreover, we will discuss the latest guidelines on surveillance and provide an overview of the most recent developments in the field of endoscopic imaging and IBD.


Boron templated catechol phosphines as bidentate ligands in silver complexes.
Reaction of 3-[(diphenylphosphinyl)methyl]benzene-1,2-diol (1) and 4-[(diphenylphosphinyl)methyl]benzene-1,2-diol (2) with AgOTf or B(OH)3 produced the bis-phosphine complexes 4, 5, or the borates 6, 7, respectively. All products were characterised by analytical and spectroscopic data and single-crystal X-ray diffraction studies. The anionic assembly 6 was shown to act as a template-based chelate ligand toward Ag+ by forming a neutral complex 8 of composition [(6)Ag] with AgOTf. Spectroscopic and single-crystal X-ray diffraction studies revealed the presence of a kinetically very stable and conformationally rigid chelate that is best described as a bis-phosphine silver complex with a distinctly non-linear P-Ag-P array and two further secondary Ag-O interactions. Reaction of 7 with AgOTf proceeded in a 2 : 2 molar ratio to give a dimeric product 9 which was, on the basis of spectroscopic data, formulated as a macrocycle of composition [(7)(2)Ag2]. The different molecular sizes of 8 and 9 was underlined by PGSE NMR measurements which gave further evidence for the formation of solvent adducts between the chelate complex 8 and DMF. Analysis of the 1H,109Ag HMQC NMR spectra of 8 provided evidence for a dependence of the 3J(Ag,H) coupling on torsional angles which resembles a Karplus-type relationship.


[Value of estramustine phosphate in the treatment of estrogen-resistant prostatic adenocarcinoma].
Estramustine phosphate ( Estracyt ) was used in 32 patients with a mean age of 73 and a half years suffering from oestrogen-resistant carcinoma of the prostate. These carcinomas were advanced and were divided into 26 stage D and 6 stage C. Treatment was given orally at a dose of 600 mg per day. Results were assessed on the basis of reliable subjective and objective selected criteria. Objective responses were obtained in 28,1% of cases and subjective responses in 40.6%. All the patients in whom there was an objective response showed a subjective response. Objective action was more marked on the primary tumour than on metastases. There was a decrease in bone pain, an improvement in general condition and disappearance of dysuria in more than a third of all cases. When there was a response, it always occurred before the end of the 2nd month and was maximal at 3 months. The mean duration of a response was 29.1 months for objective responses and 27.7 months for subjective responses. Survival of patients responding to treatment was markedly longer (by 15 months on average) than in patients who failed to respond. The low level of toxicity of the compound, even after prolonged use, makes its use possible in all patients. Thus Estracyt is felt to have a role in the treatment of the severe forms represented by hormone-resistant carcinomas of the prostate.


Investigating the effect of cell substrate on cancer cell stiffness by optical tweezers.
The mechanical properties of cells are influenced by their microenvironment. Here we report cell stiffness alteration by changing the cell substrate stiffness for isolated cells and cells in contact with other cells. Polydimethylsiloxane (PDMS) is used to prepare soft substrates with three different stiffness values (173, 88 and 17kPa respectively). Breast cancer cells lines, namely HBL-100, MCF-7 and MDA-MB-231 with different level of aggressiveness are cultured on these substrates and their local elasticity is investigated by vertical indentation of the cell membrane. Our preliminary results show an unforeseen behavior of the MDA-MB-231 cells. When cultured on glass substrate as isolated cells, they are less stiff than the other two types of cells, in agreement with the general statement that more aggressive and metastatic cells are softer. However, when connected to other cells the stiffness of MDA-MB-231 cells becomes similar to the other two cell lines. Moreover, the stiffness of MDA-MB-231 cells cultured on soft PDMS substrates is significantly higher than the stiffness of the other cell types, demonstrating thus the strong influence of the environmental conditions on the mechanical properties of the cells.


Sequences outside recognition sets are not neutral for tRNA aminoacylation. Evidence for nonpermissive combinations of nucleotides in the acceptor stem of yeast tRNAPhe.
Phenylalanine identity of yeast tRNAPhe is governed by five nucleotides including residues A73, G20, and the three anticodon nucleotides (Sampson et al., 1989, Science 243, 1363-1366). Analysis of in vitro transcripts derived from yeast tRNAPhe and Escherichia coli tRNAAla bearing these recognition elements shows that phenylalanyl-tRNA synthetase is sensitive to additional nucleotides within the acceptor stem. Insertion of G2-C71 has dramatic negative effects in both tRNA frameworks. These effects become compensated by a second-site mutation, the insertion of the wobble G3-U70 pair, which by itself has no effect on phenylalanylation. From a mechanistic point of view, the G2-C71/G3-U70 combination is not a "classical" recognition element since its antideterminant effect is compensated for by a second-site mutation. This enlarges our understanding of tRNA identity that appears not only to be the outcome of a combination of positive and negative signals forming the so-called recognition/identity set but that is also based on the presence of nonrandom combinations of sequences elsewhere in tRNA. These sequences, we name "permissive elements," are retained by evolution so that they do not hinder aminoacylation. Likely, no nucleotide within a tRNA is of random nature but has been selected so that a tRNA can fulfill all its functions efficiently.


Activation of angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas axis attenuates the cardiac reactivity to acute emotional stress.
Recent data indicate the brain angiotensin-converting enzyme/ANG II/AT1 receptor axis enhances emotional stress responses. In this study, we investigated whether its counterregulatory axis, the angiotensin-converting enzyme 2 (ACE2)/ANG-(1-7)/Mas axis, attenuate the cardiovascular responses to acute emotional stress. In conscious male Wistar rats, the tachycardia induced by acute stress (air jet 10 l/min) was attenuated by intravenous injection of ANG-(1-7) [Δ heart rate (HR): saline 136 ± 22 vs. ANG-(1-7) 61 ± 25 beats/min; P < 0.05]. Peripheral injection of the ACE2 activator compound, XNT, abolished the tachycardia induced by acute stress. We found a similar effect after intracerebroventricular injections of either ANG-(1-7) or XNT. Under urethane anesthesia, the tachycardia evoked by the beta-adrenergic agonist was markedly reduced by ANG-(1-7) [ΔHR: saline 100 ± 16 vs. ANG-(1-7) 18 ± 15 beats/min; P < 0.05]. The increase in renal sympathetic nerve activity (RSNA) evoked by isoproterenol was also abolished after the treatment with ANG-(1-7) [ΔRSNA: saline 39% vs. ANG-(1-7) -23%; P < 0.05]. The tachycardia evoked by disinhibition of dorsomedial hypothalamus neurons, a key nucleus for the cardiovascular response to emotional stress, was reduced by ∼45% after intravenous injection of ANG-(1-7). In cardiomyocyte, the incubation with ANG-(1-7) (1 μM) markedly attenuated the increases in beating rate induced by isoproterenol. Our data show that activation of the ACE2/ANG-(1-7)/Mas axis attenuates stress-induced tachycardia. This effect might be either via the central nervous system reducing anxiety level and/or interfering with the positive chronotropy mediated by activation of cardiac β adrenergic receptors. Therefore, ANG-(1-7) might contribute to reduce the sympathetic load to the heart during situations of emotional stress, reducing the cardiovascular risk.


Silver-Catalyzed Decarboxylative Bromination of Aliphatic Carboxylic Acids.
The silver-catalyzed Hunsdiecker bromination of aliphatic carboxylic acids is described. With Ag(Phen)2OTf as the catalyst and dibromoisocyanuric acid as the brominating agent, various aliphatic carboxylic acids underwent decarboxylative bromination to provide the corresponding alkyl bromides under mild conditions. This method not only is efficient and general but also enjoys wide functional group compatibility. An oxidative radical mechanism involving Ag(II) intermediates is proposed.


Giant left atrial myxoma causing severe pulmonary hypertension.
This report describes a case of giant left atrial myxoma in a 43-year-old woman. She presented with general malaise and dyspnea. Electrocardiogram showed severe right-axis deviation. Transthoracic echocardiography demonstrated a giant mobile mass with size of 6.5 × 4.5 cm in the left atrium. This mass protruded into the left ventricle in diastole and disturbed transmitral left ventricular filling flow. Bilateral atrium and right ventricle were dilated. Severe tricuspid regurgitation was demonstrated with peak pressure gradient of 91 mmHg. This mass was surgically excised and was diagnosed as benign atrial myxoma by histological analysis. Pulmonary hypertension was improved after surgery.


Kidney epithelium specific deletion of kelch-like ECH-associated protein 1 (Keap1) causes hydronephrosis in mice.
Transcription factor Nrf2 protects from experimental acute kidney injury (AKI) and is promising to limit progression in human chronic kidney disease (CKD) by upregulating multiple antioxidant genes. We recently demonstrated that deletion of Keap1, the endogenous inhibitor of Nrf2, in T lymphocytes significantly protects from AKI. In this study, we investigated the effect of Keap1 deletion on Nrf2 mediated antioxidant response in the renal tubular epithelial cells. We deleted Keap1 exon 2 and 3 in the renal tubular epithelial cells by crossing Ksp-Cre mice with Keap1 floxed (Keap1 (f/f)) mice. Deletion of Keap1 gene in the kidney epithelial cells of Ksp-Keap1 (-/-) mice and its effect on Nrf2 target gene expression was performed using PCR and real-time PCR respectively. Histological evaluation was performed on H&E stained sections. Complete blood count, serum and urine analysis were performed to assess systemic effects of defective kidney development. Student's T test was used to determine statistical difference between the groups. Ksp-Cre resulted in the deletion of Keap1 exon 2 and 3 and subsequent upregulation of Nrf2 target genes, Nqo1, Gclm and Gclc in the kidney epithelial cells of Ksp-Keap1 (-/-) mice at baseline. Renal epithelial cell specific deletion of Keap1 in Ksp-Keap1 (-/-) mice caused marked renal pelvic expansion and significant compression of medullary parenchyma consistent with hydronephrosis in both (3 month-old) males and females. Kidneys from 6 month-old Ksp-Keap1 (-/-) mice showed progressive hydronephrosis. Hematological, biochemical and urinary analysis showed significantly higher red blood cell count (p = 0.04), hemoglobin (p = 0.01), hematocrit (p = 0.02), mean cell volume (p = 0.02) and mean cell hemoglobin concentration (p = 0.003) in Ksp-Keap1 (-/-) mice in comparison to Keap1 (f/f) mice. These unexpected findings demonstrate that Keap1 deletion in renal tubular epithelial cells results in an abnormal kidney development consistent with hydronephrosis and reveals a novel Keap1 mediated signaling pathway in renal development.


A capuchin monkey (Cebus apella) uses video to find food.
We examined the ability of capuchin monkeys to use video without immediate visual-kinaesthetic feedback as a source of information to guide their action in the 3-dimensional world. In experiment 1, 2 capuchins learned to retrieve food under 1 of 2 different objects in 1 cage after watching the experimenter hiding food under 1 of 2 replica objects while in another cage. Information space and retrieval space were thus separate. The performance criterion was 71% first correct choices in blocks of 24 trials. However, when the subjects watched prerecorded videos of the hiding events, they chose randomly. In experiment 2, we gave the capuchins further trials with video and we enhanced the object shapes by line drawings. One capuchin eventually learned to use the video clips to locate food and he generalized this learning to 2 new objects.


IMAGING DIAGNOSIS-MAGNETIC RESONANCE IMAGING FEATURES OF CRANIOMANDIBULAR OSTEOPATHY IN AN AIREDALE TERRIER.
An Airedale Terrier was presented for evaluation of depression and reluctance to be touched on the head. Magnetic resonance (MR) imaging of the head was performed. The images revealed bone lesions affecting the calvarium at the level of the coronal suture and left mandibular ramus, with focal cortical destruction, expansion, and reactive new bone formation. Skull lesions were hypointense on T1-weighted sequences, hyperintense on T2-weighted sequences, and showed an intense and homogeneous enhancement after gadolinium administration. Reactive new bone formation and periosteal proliferation were confirmed histopathologically. The clinical signs, imaging findings, and histopathological examination were consistent with craniomandibular osteopathy.


Fast Repetition Rate Fluorometry (FRRF) Derived Phytoplankton Primary Productivity in the Bay of Bengal.
The approach of fast repetition rate fluorometry (FRRF) requires a conversion factor (Φe : C/n PSII) to derive ecologically-relevant carbon uptake rates (PP z,t). However, the required Φe : C/n PSII is commonly measured by 14C assimilation and varies greatly across phytoplankton taxonomy and environmental conditions. Consequently, the use of FRRF to estimate gross primary productivity (GP z,t), alone or in combination with other approaches, has been restricted by both inherent conversion and procedural inconsistencies. Within this study, based on a hypothesis that the non-photochemical quenching (NPQNSV) can be used as a proxy for the variability and magnitude of Φe : C/n PSII, we thus proposed an independent field model coupling with the NPQNSV-based Φe : C/n PSII for FRRF-derived carbon, without the need for additional Φe : C/n PSII in the Bay of Bengal (BOB). Therewith, this robust algorithm was verified by the parallel measures of electron transport rates and 14C-uptake PP z,t. NPQNSV is theoretically caused by the effects of excess irradiance pressure, however, it showed a light and depth-independent response on large spatial scales of the BOB. Trends observed for the maximum quantum efficiency (Fv/Fm), the quantum efficiency of energy conversion ( F q ' / F m ' ) and the efficiency of charge separation ( F q ' / F v ' ) were similar and representative, which displayed a relative maximum at the subsurface and were collectively limited by excess irradiance. In particular, most observed values of Fv/Fm in the BOB were only about half of the values expected for nutrient replete phytoplankton. FRRF-based estimates of electron transport at PSII (ETRRCII) varied significantly, from 0.01 to 8.01 mol e- mol RCII-1 s-1, and showed profound responses to depth and irradiance across the BOB, but fitting with the logistic model. N, P, and irradiance are key environmental drivers in explaining the broad-scale variability of photosynthetic parameters. Furthermore, taxonomic shifts and physiological changes may be better predictors of photosynthetic parameters, and facilitate the selection of better adapted species to optimize photosynthetic efficiency under any particular set of ambient light condition.


Genetic variance and genotype-by-environment interaction of immune response in Aedes aegypti (Diptera: Culicidae).
Immune response can be negatively affected by resource limitation, so it is expected that organisms evolve strategies to minimize the impact of this environmental outcome. Phenotypic plasticity in immune response could represent a genetic response to face such situations. We investigated the effects of high and low quality and quantity of food at the larval stage on two important immune components, phenoloxidase activity (PO) and nitric oxide production (NO) measured in adults of the Dengue vector, Aedes aegypti. We reared families to determine the magnitude and pattern of expression of genetic variance, environmental variance and genotype-by-environment interaction (GEI). In addition, we quantified whether there were differences in plastic immune responses in both sexes. Our results indicated additive variance for PO and NO, but rearing environment did not produce differences among individuals. For NO and PO in males, there were large differences among families in plasticity, as indicated by the different slopes produced by each reaction norm. Therefore, there is additive genetic variation in plasticity for NO production and PO activity. One possible interpretation of these results is that different genotypes may be favored to fight pathogens under the different food quality situations. Males and females showed similar overall GEI strategies but there were differences in PO and NO. Males showed a phenotypic correlation between PO and NO, but we did not find genetic correlations between immune parameters in both sexes.