Antigenic relationships among various interferon species.
Mouse L-cell interferon consists of two antigenically distinct species, F (22 to 24K) and S(32 to 40K). Various type I mouse interferons, regardless of lymphoid or nonlymphoid origin, likewise consist of two species, whose antigenicities are indistinguishable from the two L-cell interferons. Interferon F was found to be completely neutralizable by an antiserum against human leukocyte interferon, suggesting a structural similarity between the important species of human and mouse interferons.


[Thoughts on the definition of postherpetic pain: the time criterion adds nothing].
In postherpetic neuralgia, as in all types of neuropathic pain, it is generally accepted that outcome can be affected early management with specific analgesics. However, when one looks at the diagnostic criteria appearing in the literature, there is no consensus. Authors use the notion of latency to situate the onset of postherpetic neuralgia within the continuum of herpetic pain. Depending on the Author, this latency period ranges from one to six Months after the skin eruption. This latency is poorly compatible with early intervention and not well-adapted to everyday practice. With the aim of finding ways to improve the management of pain, the Neuropathic Pain Expert Group agreed upon a new definition. Postherpetic neuralgia is pain in the involved site after the skin eruption has healed and which displays the features of neuropathic pain. This definition, which does away with the latency criterion, is based on the identification of one or more clinical features of neuropathic pain in a situation of treatment failure, namely: presence of chronic unsolicited pain (burning, tightness, pressure) and/or paroxysmal pain (tingling, stabbing pain) and/or mechanical hyperalgia/allodynia (to friction or pressure) and/or temperature sensitivity (to heat and/or cold). Such pain occurs in circumscribed neurologic zones in which a sensory deficit can be demonstrated and is usually associated with dysesthesia and/or paresthesia.


Gene transfer of noncleavable cell surface mutants of human CD154 induces the immune response and diminishes systemic inflammatory reactions.
CD154 (CD40-ligand) is a critical transmembrane molecule with potent immune-stimulatory properties that is used in clinical applications of gene therapy for leukemia and lymphoma. However, CD154 is cleaved into a soluble form, and high levels of sCD154 contribute to systemic inflammatory and cardiovascular diseases, suggesting a deleterious side effect of CD154 gene therapy. In this study, we engineered noncleavable mutants of human CD154 with point mutations to develop a potentially less toxic molecule in vivo. In contrast to wild-type CD154 (CD154-WT) subsequently released as sCD154, both mutants CD154-M3 and CD154-M4 were resistant to cleavage in tumor cells. Also, CD40-expressing leukemia B cells transfected with CD154-M3 mutant were highly effective stimulators in a mixed lymphocyte-leukemia reaction, indicating that CD154-M3 mutant did not lose biologic activity. In mice transplanted with tumors expressing CD154-WT, we found increased plasma levels of human sCD154 followed by various systemic inflammatory reactions such as glomerulonephritis and an increased number of infiltrating mononuclear cells in the liver. However, CD154-M3 mutant did not induce any systemic inflammatory effects in vivo. As such, the noncleavable mutant of CD154 is fully capable of inducing the immune response with less toxic properties and is a useful tool for CD154 immune gene therapy.


[Gas leakage from an anesthetic circuit caused by mis-installation of a canister].
We report a case of gas leakage from an anesthetic circuit, due to mis-installation of a different but very similar canister. A 56-year-old woman was scheduled for a pylogastrectomy. We planned to use a Mera MD757XLV anesthesia machine. At preoperative checking of the anesthetic machine, there was a gas leak from the anesthesia circuit without apparent reasons. We therefore had to use another anesthetic machine, MD705XL, which showed no gas leakage and was used without problems during anesthesia. Closed examination after the operation showed that the gas leakage from the MD757XLV machine occurred, because one of two canisters was wrongly replaced by a canister of MD705XL. The shapes of canisters of these two anesthesia machines look very similar, but there are crucial differences in their specifications, but even the manufacturer did not notice. These unnoticeable differences led to mis-installation of canisters, and one machine provided an airtight seal whereas the other did not. Both manufacturer and users should be aware of this danger.


5S ribosomal RNA sequence of Pneumocystis carinii and its phylogenetic association with "Rhizopoda/Myxomycota/Zygomycota group".
The cytoplasmic 5S ribosomal RNA sequence from Pneumocystis carinii was determined and compared with those of 382 eukaryotes and an evolutionary tree was constructed to establish the phylogenetic position of Pneumocystis. The data suggest that Pneumocystis is associated with the Rhizopoda/Myxomycota/Zygomycota group but not with common fungi, such as Ascomycota or Basidiomycota, nor with other protozoa.


Overcoming liability concerns in vaccine trials involving pregnant women.
Without the protection of vaccines, the health of pregnant women may be compromised. But assessing the safety and efficacy of vaccines in pregnancy requires research in pregnancy. Furthermore, vaccinating women while they are pregnant may convey immunity to the fetus in utero, but assessing this possible benefit of maternal immunization also requires research. This article argues that one factor inhibiting vaccine research involving pregnant women is that vaccine manufacturers fear incurring liability if they fund such research. We argue that vaccine research in pregnancy can be ethical, and we explore some methods for overcoming vaccine manufacturers' fear of liability.


A systems thinking approach to analysis of the Patient Protection and Affordable Care Act.
The public health community is challenged with understanding the many complexities presented by systems thinking and its applications in systems modeling. The model presented encompasses multiple variables needed (eg, model building) for the construction of a conceptual system model of the Patient Protection and Affordable Care Act (ACA). The model tracks the ACA from inception, through passage, March 2010, to its current state. Justification for the need to reform the current health care system rests, in part, on the heels of social justice. Proponents of the ACA have long argued that health reform was needed by the millions of uninsured person who suffered from health disparities, took little advantage of health prevention advice, and faced issues of access to providers as well as insurers. In addition the ACA seeks to address our uncontrollable spending on health care delivery. This article highlights the ACA from a systems perspective. The conceptual model presented encompasses both health reform variables (eg, health care provisions, key legislative components, system environment) and system variables (eg, inputs, outputs, feedback, and throughput) needed to understand current health care reform efforts from a systems perspective. The model presented shows how the interrelationships and interconnections of elements of a system come together to achieve its purpose or goal.


Quantifying health services use for chronic obstructive pulmonary disease.
Chronic obstructive pulmonary disease (COPD), a common manageable condition, is a leading cause of death. A better understanding of its impact on health-care systems would inform strategies to reduce its burden. To quantify health services use in a large, North American COPD population. We conducted a cohort study using health administrative data from Ontario, a province with a population of 13 million and universal health-care insurance. All individuals with physician-diagnosed COPD in 2008 were identified and followed for 3 years. Proportions of all hospital visits, emergency department visits, ambulatory care visits, long-term care residence places, and homecare made or used by people with COPD were determined and rates of each compared between people with and without COPD. A total of 853,438 individuals with COPD (11.8% of the population aged 35 yr and older) were responsible for 24% of hospitalizations, 24% of emergency department visits, and 21% of ambulatory care visits; filled 35% of long-term care places; and used 30% of homecare services. After adjusting for several factors, people with COPD had rates of hospital, emergency department, and ambulatory care visits that were, respectively, 63%, 85%, and 48% higher than the rest of the population. Their rates of long-term care and homecare use were 56 and 59% higher, respectively. Individuals with COPD use large and disproportionate amounts of health services. Strategies that target this group are needed to improve their health and minimize their need for health services.


Structural design of an improved SPIDER optical system based on a multimode interference coupler.
The Segmented Planar Imaging Detector for Electro-Optical Reconnaissance (SPIDER) is a small volume, lightweight, low energy consumption, and high-resolution system expected to replace traditional large aperture telescopes for long-distance detection. In this paper, an improved SPIDER system is proposed, which uses a multimode interference (MMI) coupler instead of an orthogonal detector, and successfully doubles the space spectrum coverage. We present a three-point configuring method to configure lenslets, calculate spatial spectrum values from the output currents obtained by MMI. By comparing the performance of the MMI-SPIDER and SPIDER systems through simulations, we demonstrate that the former has more complete spatial spectrum coverage, resulting in better image restoration quality.


[Deep breathing test type I diabetic patients and parameters of spectral analysis].
Nervous system injury, affecting also its autonomic part, occurs in the natural course of chronic complications in patients with type 1 and 2 diabetes. The aim of the study was to compare heart rate frequency analysis parameters at rest and after deep breathing test in healthy persons and in the group of type 1 diabetes patients without complications. The study was performed in 34 patients with type 1 diabetes without chronic complications (N0), hospitalized in the Chair and Department of Metabolic Diseases in 1993-1996. The control group (K) consisted of 23 healthy persons. All diabetic patients underwent examinations to identify chronic complications of the disease. Aiming at answering the question how simple physiological tests influence frequency parameters of heart rate variability, assessment of VLF, LF and HF parameters was performed at rest and after the deep breathing test. In both groups K and N0 no changes were observed in the spectrum power within VLF values after deep breathing compared to the initial values. In the group K the deep breathing test significantly (p < 0.001) increased spectrum power within LF values, whereas in the group N0 the test did not produce statistically significant changes of this parameter compared to the initial values. In the control group K as well as in diabetic patients N0 the test caused significant (p < 0.01 and p < 0.001, respectively) decrease in the HF spectrum power in comparison to the values at rest. VLF/LF ratio after the deep breathing test as well as LF/HF ratio at rest were significantly lower in the group K compared to the group N0. Analysis of the autonomic nervous system imbalance may be an indispensable tool in the early diagnostics of patients with type 1 diabetes. Results of spectrum analysis may be useful in cases when classical Ewing battery tests do not identify autonomic dysfunction.


Ipsilateral Motor Innervation Discovered Incidentally on Intraoperative Monitoring: A Case Report.
Lesions in the corticospinal tract above the decussation at the medullary pyramids almost universally produce contralateral deficits. Rare cases of supratentorial lesions causing ipsilateral motor deficits have been reported previously, but only ever found secondary to stroke or congenital pyramidal tract malformations. Herein, we report a case of ipsilateral corticospinal tract innervation discovered incidentally with intraoperative monitoring during a microsurgical resection of a vestibular schwannoma. Intraoperative monitoring with electrical transcranial stimulation of the frontal scalp triggered motor-evoked potentials in the ipsilateral arms. The uncrossed pathways were later confirmed with MRI tractography using diffusion tensor imaging. To the best of our knowledge, this is the first case of isolated ipsilateral motor innervation of the corticospinal tract discovered incidentally during a neurosurgical procedure. Given the increasing use of intraoperative monitoring, this case underscores the importance of cautious interpretation of seemingly discordant neurophysiological findings. Once technical issues have been ruled out, ipsilateral motor innervation may be considered as a possible explanation and neurosurgeons should be aware of the existence of this rare anatomic variant.


Foam films stabilized by dodecyl maltoside. 1. Film thickness and free energy of film formation.
Foam films stabilized by a sugar-based nonionic surfactant, beta-dodecyl maltoside, are investigated. The film thickness and the film contact angle (which is formed at the transition between the film and the bulk solution) are measured as a function of NaCl concentration, surfactant concentration, and temperature. The film thickness measurements provide information about the balance of the surface forces in the film whereas the contact angle measurements provide information about the specific film interaction free energy. The use of the glass ring cell and the thin film pressure balance methods enables studies under a large variety of conditions. Thick foam films are formed at low electrolyte concentration. The film thickness decreases (respectively the absolute value of the interaction film free energy increases) with the increase of the electrolyte concentration according to the classical DLVO theory. This indicates the existence of a repulsive double layer electrostatic component of the disjoining pressure. An electrostatic double layer potential of 16 mV was calculated from the data. A decrease of the film thickness on increase of the surfactant concentration in the solution is observed. The results are interpreted on the basis of the assumption that the surface double layer potential originates in the adsorption of hydroxyl ions at the film surfaces. These ions are expelled from the surface at higher surfactant concentration.


Sensitivity of solid culture, broth culture, and real-time PCR assays for milk and colostrum samples from Mycobacterium avium ssp. paratuberculosis-infectious dairy cows.
Mycobacterium avium ssp. paratuberculosis (MAP) can be shed in feces, milk, and colostrum. The goal of this study was to assess assays that detect MAP in these sample types, including effects of lactation stage or season. Understanding the performance of these assays could improve how they are used, limiting the risk of infection to calves. Forty-six previously confirmed MAP-positive cows from 7 Atlantic Canadian dairy farms were identified for colostrum sampling and monthly sampling of milk and feces over a 12-mo period. Samples were assayed for MAP using solid culture, broth culture, and direct real-time PCR (qPCR). Across assay types, test sensitivity when applied to milk samples averaged 25% of that when applied to fecal samples. For colostrum samples, sensitivity depended on assay type, with sensitivity of qPCR being approximately 46% of that in feces. Across sample types, sensitivity of qPCR was higher than that of the other assays. Sensitivity of qPCR, when applied to milk samples, was significantly higher in summer than in other seasons. Summer was also the season with highest agreement between milk and fecal samples collected within the same month. Our results suggest that qPCR would detect more cows shedding MAP in their milk and colostrum than solid or broth culture assays, particularly during the summer, thus providing better management information to limit exposure of calves to this infectious organism.


Use of human amniotic epithelial cells as a feeder layer to support undifferentiated growth of mouse spermatogonial stem cells via epigenetic regulation of the Nanog and Oct-4 promoters.
Spermatogonial stem cells (SSCs) are defined by unique properties like other stem cells. However, there are two major challenges: long-term cultivation of normal SSCs into stable cell lines and maintaining the SSCs as undifferentiated and capable of self-renewal. Here, we compared different culture methods for mouse SSCs isolated and cultured from testicular tissue. We found that human amniotic epithelial cells (hAECs) can behave as feeder cells, allowing mouse SSCs to maintain a high level of alkaline phosphatase (AP) activity when cultured long-term. Also, we observed that expression of Nanog, Oct-4 and other important stem cells markers were higher in mouse SSCs cultured on hAECs compared to those cultured on MEF or without any feeder cells. Furthermore, we demonstrated that the CpG islands of the Nanog and Oct-4 promoters were hypomethylated in cells cultured on hAECs. In addition, mouse SSCs cultured on hAECs exhibited higher levels of H3AC and H3K4Me3 in the Nanog and Oct-4 promoters than those cultured on MEF or without feeder cells. Taken together, these results suggest that the hAEC-induced epigenetic modifications at the Nanog and Oct-4 locus could be a key mechanism for maintaining mouse SSCs in an undifferentiated state capable of self-renewal.


Cilostazol, a Phosphodiesterase 3 Inhibitor, Moderately Attenuates Behaviors Depending on Sex in the Ts65Dn Mouse Model of Down Syndrome.
People with Down syndrome, which is a trisomy of chromosome 21, exhibit intellectual disability from infancy and neuropathology similar to Alzheimer's disease, such as amyloid plaques, from an early age. Recently, we showed that cilostazol, a selective inhibitor of phosphodiesterase (PDE) 3, promotes the clearance of amyloid β and rescues cognitive deficits in a mouse model of Alzheimer's disease. The objective of the present study was to examine whether cilostazol improves behaviors in the most widely used animal model of Down syndrome, i.e., Ts65Dn mice. Mice were supplemented with cilostazol from the fetal period until young adulthood. Supplementation significantly ameliorated novel-object recognition in Ts65Dn females and partially ameliorated sensorimotor function as determined by the rotarod test in Ts65Dn females and hyperactive locomotion in Ts65Dn males. Cilostazol supplementation significantly shortened swimming distance in Ts65Dn males in the Morris water maze test, suggesting that the drug improved cognitive function, although it did not shorten swimming duration, which was due to decreased swimming speed. Thus, this study suggests that early supplementation with cilostazol partially rescues behavioral abnormalities seen in Down syndrome and indicates that the effects are sex-dependent.


Familial Hodgkin's disease. A clinical and laboratory investigation.
A three to sevenfold increased risk of Hodgkin's disease has been noted in families of patients. We report the first family in which all four of a four member sibship had Hodgkin's disease. In these four sibling cases, we were able to explore markers of infectious etiologic factors by measuring antibodies to Epstein-Barr virus (EBV) and human T-cell lymphotropic virus (HTLV), and possible genetic risk factors by human leukocyte antigen (HLA) typing and chromosome analysis. All three men were diagnosed within six months of their 30th birthday. HLA typing revealed that all four siblings share the DR5 antigen, and two siblings share HLA-B27. Chromosome analysis on peripheral lymphocytes revealed no abnormalities. A detailed, structured interview failed to elicit evidence of unusual exposures. The EBV antibody titers are probably within the normal range and none of the family had antibodies to HTLV-III. Observations on this family suggest that genetic factors play a greater role than environmental factors in the etiology of familial Hodgkin's disease.


Glyco-modification of protein with O-cyanate chain-end functionalized glycopolymer via isourea bond formation.
Glycoengineering aimed at addition of carbohydrates to proteins is an attractive approach to alter pharmacokinetic properties of proteins such as enhancing stability and prolonging the duration of action. We report a novel protein glyco-modification of BSA and recombinant thrombomodulin with O-cyanate chain-end functionalized glycopolymer via isourea bond formation. The protein glycoconjugates were confirmed by SDS-PAGE, western blot, and MALDI-TOF Mass Spectrometry. Protein C activation activity of the glyco-modified recombinant thrombomodulin was confirmed, proving no interference to activity from the glycopolymer modification. The isourea bond formation under mild conditions was demonstrated as an alternative method for protein modification with polymers.


Molecular and ultrastructural characterization of porcine hippurate-negative Brachyspira pilosicoli.
Brachyspira pilosicoli, the causative agent of porcine intestinal spirochetosis, usually has hippurate-cleaving capacity. We have regularly isolated hippurate-negative B. pilosicoli from cases of porcine diarrhea. In this study, we show that these biochemically atypical B. pilosicoli isolates can be classified as B. pilosicoli. 16S ribosomal DNA was partially sequenced from eight hippurate-negative and two hippurate-positive B. pilosicoli-like isolates from seven herds. The differences in nucleotide sequence with B. pilosicoli P43/6/78 type strain were not associated with hippurate cleavage. In 877 bp, the hippurate-negative isolates had a similarity of 98.63 to 100% to the type strain, with the corresponding figures for the two hippurate-positive isolates being 98.86 and 100%. The nucleotide sequences of hippurate-positive isolates were identical to the respective sequences of hippurate-negative isolates from one herd. The DNA macrorestriction patterns of a total of 20 hippurate-negative and -positive B. pilosicoli isolates were diverse, and no clustering in conjunction with the hippurate reaction was found. In two herds, hippurate-positive and -negative B. pilosicoli isolates had a common macrorestriction pattern. The ultrastructure of hippurate-negative isolates was similar to the type strain. In conclusion, B. pilosicoli can be either hippurate positive or negative and, thus, the scheme for biochemical differentiation of porcine Brachyspira should be revised to include identification of hippurate-negative B. pilosicoli.


Biosynthesis of alpha-fetoprotein in cultured hepatoma cells.
Pulse and pulse-chase experiments demonstrated that a heterogeneous polypeptide with an apparent Mr = 68,000 was the first intracellular anti-alpha-fetoprotein (AFP)-precipitable polypeptide synthesized by rat Mc-A-RH-7777 hepatoma cells. The 68,000-dalton polypeptide may consist of polypeptides with apparent molecular weights ranging from 68,000 to 70,000. It was the precursor of two intracellular anti-AFP-precipitable polypeptides of 69,000 and 73,000 apparent molecular weight. The latter were secreted into the medium without further processing. The anti-AFP-precipitable polypeptides in both cells and medium incorporated [3H]glucosamine, indicating that these polypeptides are at least partially glycosylated. The 68,000-dalton polypeptide in cells was bound mostly to concanavalin A-Sepharose, whereas the 69,000-dalton polypeptide was entirely unbound. The 73,000-dalton polypeptide consisted of concanavalin A-bound and -unbound variants. Tunicamycin completely abolished the uptake of [3H]glucosamine into anti-AFT-precipitable polypeptides in both cells and medium, and the resulting polypeptide of apparent Mr = 66,000 did not bind to concanavalin A-Sepharose. Tunicamycin did not affect the synthesis or secretion of AFP by hepatoma cells.


[Determination of body fluid based on analysis of nucleic acids].
Recent methodological approaches of molecular genetics allow isolation of nucleic acids (DNA and RNA) from negligible forensic samples. Analysis of these molecules may be used not only for individual identification based on DNA profiling but also for the detection of origin of the body fluid which (alone or in mixture with other body fluids) forms the examined biological trace. Such an examination can contribute to the evaluation of procedural, technical and tactical value of the trace. Molecular genetic approaches discussed in the review offer new possibilities in comparison with traditional spectrum of chemical, immunological and spectroscopic tests especially with regard to the interpretation of mixtures of biological fluids and to the confirmatory character of the tests. Approaches based on reverse transcription of tissue specific mRNA and their subsequent polymerase chain reaction (PCR) and fragmentation analysis are applicable on samples containing minimal amounts of biological material. Methods for body fluid discrimination based on examination of microRNA in samples provided so far confusing results therefore further development in this field is needed. The examination of tissue specific methylation of nucleotides in selected gene sequences seems to represent a promising enrichment of the methodological spectrum. The detection of DNA sequences of tissue related bacteria has been established and it provides satisfactory results mainly in combination with above mentioned methodological approaches.


Helper factor production in murine secondary syngeneic mixed leukocyte reactions.
Culture supernatants of murine thymocytes or spleen cells responding in a secondary syngeneic mixed leukocyte reaction (SMLR) were studied for their biologic effects on cell-mediated immune responses in vitro. Such supernatants contained helper factor(s) that facilitated the development of alloantigen-specific cytotoxic T lymphocyte (CTL) responses from thymocyte precursors. Thymocytes, but not spleen cells, required activation by allogeneic effect factor (AEF) in primary culture in order to proliferate and produce biologically active mediator(s) during a secondary SMLR. The same culture supernatants possessed, in some instances, weak T cell growth factor (TCGF; IL 2) activity. However, TCGF activity could be dissociated from helper factor(s) active in the CTL induction assay because some culture supernatants that had potent helper activity were devoid of TCGF activity. This lack of TCGF activity was not due to a lower degree of sensitivity of the TCGF assay or to the presence of a selective TCGF inhibitor in the SMLR-derived supernatants, indicating that the helper factor(s) studied is distinct from TCGF. Production of immunoregulatory lymphokines during the SMLR may serve as a physiologically relevant model for studying the role of T cell-derived lymphokines in immunoregulation.


Chemoenzymatic Oxosulfonylation-Bioreduction Sequence for the Stereoselective Synthesis of β-Hydroxy Sulfones.
A series of optically active β-hydroxy sulfones has been obtained through an oxosulfonylation-stereoselective reduction sequence in aqueous medium. Firstly, β-keto sulfones were synthesized from arylacetylenes and sodium sulfinates to subsequently develop the carbonyl reduction in a highly selective fashion using alcohol dehydrogenases as biocatalysts. Optimization of the chemical oxosulfonylation reaction was investigated, finding inexpensive iron(III) chloride hexahydrate (FeCl3 ⋅ 6H2 O) as the catalyst of choice. The selection of isopropanol in the alcohol-water media resulted in high compatibility with the enzymatic process for enzyme cofactor recycling purposes, providing a straightforward access to both (R)- and (S)-β-hydroxy sulfones. The practical usefulness of this transformation was illustrated by describing the synthesis of a chiral intermediate of Apremilast. Interestingly, the development of a chemoenzymatic cascade approach avoided the isolation of β-keto sulfone intermediates, which allowed the preparation of chiral β-hydroxy sulfones in high conversion values (83-94 %) and excellent optical purities (94 to >99 % ee).


Facile approach to prepare nickel cobaltite nanowire materials for supercapacitors.
Excellent electrochemical performance results from the coexistence of nickel and cobalt ions, with mesoporous characteristics and nanocrystal structure. Nickel cobalt nanowire is prepared by hydrothermal and thermal decomposition processes. High capacitance of 722 F g(-1) can be obtained at 1 A g(-1) in 6 M KOH, with a capacitance retention ratio of ca. 79% at 20 A g(-1) .


Mean platelet volume is elevated during paroxysmal atrial fibrillation: a marker of increased platelet activation?
Paroxysmal atrial fibrillation might be a risk factor for stroke such as chronic atrial fibrillation. We examined the relation between mean platelet volume and paroxysmal atrial fibrillation to determine the effect of paroxysmal atrial fibrillation on the thrombotic state via elevated mean platelet volume. Mean platelet volume is a marker of platelet size, function, and activation. Increased mean platelet volume reflects active and large platelets that release more thromboxane A2 than smaller ones. We hypothesized that mean platelet volume is elevated in patients with paroxysmal atrial fibrillation. The study population comprised 103 consecutive patients who were detected to have paroxysmal atrial fibrillation by 24-h Holter monitoring and 87 control individuals with normal Holter monitoring. Mean platelet volume and inflammatory parameters were measured. Comprehensive clinical and echocardiographic data were collected. Patients with aortic and mitral stenosis, hyperthyroidism, hypothyroidism, malignancy, infection, and pregnancy were excluded from the study. Mean age of the patients was 63 +/- 11 vs. 45 +/- 14 years (P < 0.001) in paroxysmal atrial fibrillation and control groups, respectively. Fifty-seven patients (55%) in paroxysmal atrial fibrillation and 19 (21%) (P < 0.001) patients in control group were men. Mean platelet volume was significantly higher in the paroxysmal atrial fibrillation group when compared with control group (10.0 +/- 2.0 vs. 8.3 +/- 1.5 fl, respectively; P < 0.001). C-reactive protein (18.5 +/- 28 vs. 3.8 +/- 2 mg/l, respectively; P = 0.004) and erythrocyte sedimentation rate (21 +/- 21 vs. 12 +/- 7 mm/h, respectively; P = 0.01) were also higher in the paroxysmal atrial fibrillation group. There was no difference in white blood cell and platelet counts between groups. In a multivariate analysis, elevated mean platelet volume was associated with the occurrence of paroxysmal atrial fibrillation before and after adjustment for age and sex. Our results indicate that inflammatory markers such as C-reactive protein and erythrocyte sedimentation rate and the marker of platelet size and activity mean platelet volume are elevated in patients with paroxysmal atrial fibrillation.


Enhanced Optical Transmission through a Hybrid Bull's Eye Structure Integrated with a Silicon Hemisphere.
In this work, we demonstrate a novel structure that can generate extraordinary optical transmission with a silicon hemisphere placed on a conventional bull's eye structure. There is a single subwavelength aperture surrounded by concentric periodic grooves on a substrate. The extraordinary optical transmission in this work is realized by the coupling of the surface plasmon polaritons in the periodic grooves and the localized electromagnetic field generated by the Mie resonance in the silicon hemisphere. The maximum normalized-to-area transmission peak can reach up to 662 with a decreasing device area and size. The electromagnetic field distribution at different geometry parameters is analyzed to clarify the mechanisms of the work in this paper. Additionally, the use of dielectric material in the aperture can avoid ohmic losses of metal material compared with the conventional one, which may suggest that a wider range of bull's-eye-structure applications is possible.


Can the UNAIDS 90-90-90 target be achieved? A systematic analysis of national HIV treatment cascades.
In 2014, the Joint United Nations Programme on HIV and AIDS (UNAIDS) and partners set the '90-90-90 targets'; aiming to diagnose 90% of all HIV positive people, provide antiretroviral therapy (ART) for 90% of those diagnosed and achieve viral suppression for 90% of those treated, by 2020. This results in 81% of all HIV positive people on treatment and 73% of all HIV positive people achieving viral suppression. We aimed to analyse how effective national HIV treatment programmes are at meeting these targets, using HIV care continuums or cascades. We searched for HIV treatment cascades for 196 countries in published papers, conference presentations, UNAIDS databases and national reports. Cascades were constructed using reliable, generalisable, recent data from national, cross-sectional and longitudinal study cohorts. Data were collected for four stages; total HIV positive people, diagnosed, on treatment and virally suppressed. The cascades were categorised as complete (four stages) or partial (3 stages), and analysed for 'break points' defined as a drop >10% in coverage between consecutive 90-90-90 targets. 69 country cascades were analysed (32 complete, 37 partial). Diagnosis (target one-90%) ranged from 87% (the Netherlands) to 11% (Yemen). Treatment coverage (target two-81% on ART) ranged from 71% (Switzerland) to 3% (Afghanistan). Viral suppression (target three-73% virally suppressed) was between 68% (Switzerland) and 7% (China). No country analysed met the 90-90-90 targets. Diagnosis was the greatest break point globally, but the most frequent key break point for individual countries was providing ART to those diagnosed. Large disparities were identified between countries. Without commitment to standardised reporting methodologies, international comparisons are complex.


Interference of guided modes in a two-port ring waveguide composed of dielectric nanoparticles.
The interference is considered of guided polariton modes in a two-port ring waveguide composed of dielectric nanospheres. The dependence of the guided polariton intensity on the relative orientation of the input and output channels is investigated. It is shown that, if the frequency of the external light source corresponds to one of the resonant modes of the waveguide ring segment, the guided polariton may be treated as two optical beams running along the ring segment in the opposite directions and interfering with each other. The multisphere Mie scattering formalism is used. The dipole approximation is shown to grasp the essence of physics. Our simple interpretation of the results is obtained in terms of scalar waves. The applications of the interference revealed in the manuscript are discussed as well.


Acidosis regulates the stability, hydrophobicity, and activity of the BH3-only protein Bnip3.
Bnip3 is a prodeath member of the so-called BH3-only subfamily of Bcl-2 proteins. A major function of this class of proteins is to regulate the permeability state of the outer mitochondrial membrane by forming homoand hetero-oligomers inside the membrane. We reported previously that Bnip3 accumulates in cardiac myocytes during exposure to hypoxia, but coincident acidosis is required to activate the death program. Acidosis increased the rate of intracellular accumulation of Bnip3 and promoted a tighter association with mitochondria. Here we report that acidic pH mediates increased half-lives of Bnip3 dimers and monomers (>3-) as well as that of a faster-migrating fragment (>10-) and confers protection against degradation by protease. Hydrophobic partitioning experiments revealed that Bnip3 monomers and oligomers from hypoxia-acidic cell fractions associated significantly with the detergent layer, whereas protein from hypoxia-neutral myocytes did not. Acidosis promoted homodimerization of Bcl-xL but did not increase its association with detergent. Neutralization of the extracellular medium of cardiac myocyte cultures under hypoxia-acidosis resulted in rapid degradation of accumulated Bnip3 (half life, <2 h), coincident with cessation of the death program. Bnip3 monomers appear to be the active species because substitution of alanine for histidine at position 173 within the transmembrane (TM) domain prevented homodimerization but did not inhibit the death function. These results demonstrate a pH-sensitive shift in the stability and apparent hydrophobicity of Bnip3 monomers that correlates closely with membrane binding and function.


Phosphorylation of a twitchin-related protein controls catch and calcium sensitivity of force production in invertebrate smooth muscle.
"Catch" is a condition of prolonged, high-force maintenance at resting intracellular Ca2+ concentration ([Ca2+]) and very low energy usage, occurring in invertebrate smooth muscles, including the anterior byssus retractor muscle (ABRM) of Mytilus edulis. Relaxation from catch is rapid on serotonergic nerve stimulation in intact muscles and application of cAMP in permeabilized muscles. This release of catch occurs by protein kinase A-mediated phosphorylation of a high (approximately 600 kDa) molecular mass protein, the regulator of catch. Here, we identify the catch-regulating protein as a homologue of the mini-titin, twitchin, based on (i) a partial cDNA of the purified isolated protein showing 77% amino acid sequence identity to the kinase domain of Aplysia californica twitchin; (ii) a polyclonal antibody to a synthetic peptide in this sequence reacting with the phosphorylated catch-regulating protein band from permeabilized ABRM; and (iii) the similarity of the amino acid composition and molecular weight of the protein to twitchin. In permeabilized ABRM, at all but maximum [Ca2+], phosphorylation of twitchin results in a decreased calcium sensitivity of force production (half-maximum at 2.5 vs. 1.3 microM calcium). At a given submaximal force, with equal numbers of force generators, twitchin phosphorylation increased unloaded shortening velocity approximately 2-fold. These data suggest that aspects of the catch state exist not only at resting [Ca2+], but also at higher submaximal [Ca2+]. The mechanism that gives rise to force maintenance in catch probably operates together, to some extent, with that of cycling myosin crossbridges.


Non-invasive assessment of arterial stiffness indices by applanation tonometry and pulse wave analysis in patients with rheumatoid arthritis treated with TNF-alpha blocker remicade (infliximab).
Rheumatoid arthritis (RA) is accompanied by long lasting inflammation, which may lead to arterial dysfunction and premature aging of the arteries. The purpose of this clinical work was to determine the modification of carotid-radial pulse wave velocity (PWV) and aortic augmentation index (AIx) in young-aged RA patients and the influence of treatment with anti-TNF-alpha (infliximab) on these measures. We examined 68 RA patients (mean age 40.68 yrs) with moderate or high disease activity (DAS28 5.37 +/- 0.94) and 87 controls (mean age 38.10 yrs). PWV and AIx were assessed non-invasively by applanation tonometry. A blood test included serum lipid profile, and high-sensitivity CRP measurements. We found that in RA patients, AIx (p < 0.001) was significantly higher while PWV (p = 0.315) did not differ as compared to control. Multiple regression analysis revealed the presence of RA is an independent predictor for AIx (R2 = 0.718, adjusted R2 = 0.707; p < 0.001). Analysis (Mann-Whitney test) in 15 RA patients revealed lowering of PWV (p = 0.004) under infliximab therapy with no change in AIx (p = 0.573), suggesting the improvement of arterial wall function by anti-TNF-alpha therapy. We conclude that increased AIx is more prominent in RA patients as compared to the controls. PWV appears to be a less sensitive marker for the detection of enhanced development of arterial stiffness in relatively young-aged RA patients. However, PWV may serve as a good marker to discern effects of infliximab on artery elasticity.


Lipase activity of Mucor pusillus.
Two strains of Mucor pusillus were examined for their ability to synthesize lipase in a complex medium used in the production of milk-clotting protease. Lipase activity of both strains reached maximal after 6 days of incubation under submerged conditions at 35 C. Lipase secreted into the medium hydrolyzed butterfat and vegetable lipids, as well as selected synthetic triglycerides. About 50% of lipase activity was destroyed after a 45-min heat treatment at 58 C.


A tegument-specific venom allergen-like protein of Clonorchis sinensis.
Venom allergen-like (VAL) proteins, members of the SCP/TAPS (sperm coating protein/Tpx-1/Ag5/PR-1/Sc7) protein superfamily, have been reported from several parasitic helminths. As little is known about their biological functions, a VAL protein of the Chinese liver fluke Clonorchis sinensis was cloned and characterized. A complementary DNA (cDNA) encoding a 25-kDa protein was identified from an EST database of C. sinensis. A BLAST search revealed that the protein shares 46% sequence identity with Schistosoma mansoni VAL 13 protein, and thus, the protein was named CsVAL13. Multiple sequence alignment indicated that the SCP/TAPS domain of CsVAL13 shares 39-46% sequence identity with VAL proteins from parasitic helminths. His and Tyr, which help to stabilize protein structure, were highly conserved across the VAL protein sequences. Phylogenetic analysis showed that the SCP/TAPS domain of the CsVAL13 sequence clusters together with other group 2 VAL protein sequences. In the homology-modeled structure of CsVAL13, an α-β-α sandwich and residues for a putative active site were highly conserved. Immune sera were obtained from BALB/c mice immunized with the recombinant CsVAL13 protein. Immunohistochemical localization using the immune sera revealed that CsVAL13 was distributed mainly in the tegument and intrauterine eggs of adult C. sinensis. These findings suggest that CsVAL13 may be involved in host-parasite interactions and immune stimulation on the surrounding host environments.


Multicenter, Open-Label, Phase II Study of Bendamustine and Rituximab Followed by 90-Yttrium (Y) Ibritumomab Tiuxetan for Untreated Follicular Lymphoma (Fol-BRITe).
Bendamustine and rituximab (BR) has been established as a superior frontline therapy over R-CHOP in the treatment of follicular lymphoma (FL). Yttrium-90 Ibritumomab tiuxetan (90YIT) is an effective consolidation strategy after chemotherapy induction. This prospective, single-arm, multicenter, phase II trial evaluated the response rate, progression-free survival (PFS), and tolerability of BR followed by consolidation with 90YIT in patients with untreated FL. The study included grade 1 to 3a FL patients aged ≥18 years, chemotherapy-naïve, and requiring treatment for stage II-IV disease. Study treatment included an initial rituximab treatment, followed by four cycles of BR. Patients were eligible for consolidation with 90YIT, 6 to 12 weeks after BR, if they obtained at least a partial response after induction had adequate count recovery and bone marrow infiltration < 25%. Thirty-nine patients were treated. Eighty-two percent had an intermediate or high-risk Follicular Lymphoma International Prognostic Index score, and 6 of 39 (15%) were grade 3a. The response rate was 94.8%, and the complete response(CR)/CR unconfirmed (CRu) rate was 77% in the intention-to-treat analysis. The conversion rate from PR to CR/Cru after 90YIT was 81%. After median follow-up of 45 months, the PFS was 0.71 (95% confidence interval, 0.57-0.89). This report demonstrates that four cycles of BR followed by consolidation with 90YIT achieve high response rates that are durable. In addition, consolidation with 90YIT results in a high conversion rate of PR to CR/CRu. A short course of BR followed by 90YIT is a safe and effective regimen for frontline treatment of FL.


Unique Optical Periodicity Assembly of Discrete Dendritic Lamellae and Pyramidal Single Crystals in Poly(ε-caprolactone).
A unique zig-zag banded morphology poly(ε-caprolactone) (PCL), crystallized at high Tc = 46-47 °C and confined in thin films (<1 μm), is found to be assembled of parallel cogrowth of two totally crystal entities: edge-on dendritic lamellar protrusion from surfaces and flat-on pyramidal single crystals. The alternating PCL optical bands are assembled as flat-on single crystals aligned as straight dendrites as a valley band in series with edge-on branches as a ridge band, leading to a unique assembly mechanism of periodic optical rings where these two crystal pieces are assembled in series. Detailed assembly mechanisms are proposed to explain how the composite bands in the PCL aggregates are correlated to optical birefringence periodicity. By techniques of melt crystallization via periodic species drainage, PCL single crystals could be prepared and tailor-made to a variety of nanopatterns as templates for applications.


The interRAI Child and Youth Suite of Mental Health Assessment Instruments: An Integrated Approach to Mental Health Service Delivery.
Various biological, social, psychological, and environmental factors impact children and youth living with mental health problems across their lifespan. To meet the wide-ranging challenges of mental illness, service system integration is needed to improve efficiencies and reduce fragmentation. Unfortunately, the mental health system has been plagued by the lack of coordination across services. There is a general consensus that mental health service delivery must ensure a child or youth's needs are addressed in a collaborative, coordinated, and seamless manner. A key element to successful integration is the development of a comprehensive standardized screening and assessment system. Numerous assessments have been developed to assess child mental health and functioning, but they typically have a very narrow focus with limited use and utility. Not only does this reduce the ability to take a life course perspective to mental health, but this uncoordinated approach also results in redundancies in information collected, additional resources, and increased assessor burden for children, youth, and their families. The interRAI child and youth mental health assessment suite was developed in response to the need for an integrated mental health system for young persons. This suite includes screening and assessment instruments for in-patient and community settings, emergency departments, educational settings, and youth justice custodial facilities. The instruments form a mental health information system intentionally designed to work in an integrated fashion beginning in infancy, and incorporate key applications such as care planning, outcome measurement, resource allocation, and quality improvement. The design of these assessment tools and their psychometric properties are reviewed. Data is then presented using examples related to interpersonal trauma, illustrating the use and utility of the integrated suite, along with the various applications of these assessment systems.


Hypertrophy, pathology, and molecular markers of cardiac pathogenesis.
Increased ventricular expression of several genes, including atrial natriuretic factor (ANF), has been documented in experimental models of cardiac hypertrophy. It remains to be clarified whether altered expression of these genes is a consistent marker of the hypertrophy itself or a marker of some parallel pathogenetic process. Using a transgenic mouse model of hypertrophic cardiomyopathy as a tool, we assessed the relationship between the amount of ventricular ANF gene expression and the degree of hypertrophy as well as the relationship between the cells expressing ANF and tissue pathology. We determined that hypertrophy is not always associated with increased ventricular expression of ANF and that cells expressing ANF are found in regions of tissue pathology. We propose that alteration in the ventricular expression of this gene is a sensitive indicator of cardiac pathogenesis and may result from a number of different stimuli that include, among others, abnormal tissue architecture and hemodynamic load.


Frequency Clustering Analysis for Resting State Functional Magnetic Resonance Imaging Based on Hilbert-Huang Transform.
Objective: Exploring resting-state functional networks using functional magnetic resonance imaging (fMRI) is a hot topic in the field of brain functions. Previous studies suggested that the frequency dependence between blood oxygen level dependent (BOLD) signals may convey meaningful information regarding interactions between brain regions. Methods: In this article, we introduced a novel frequency clustering analysis method based on Hilbert-Huang Transform (HHT) and a label-replacement procedure. First, the time series from multiple predefined regions of interest (ROIs) were extracted. Second, each time series was decomposed into several intrinsic mode functions (IMFs) by using HHT. Third, the improved k-means clustering method using a label-replacement method was applied to the data of each subject to classify the ROIs into different classes. Results: Two independent resting-state fMRI dataset of healthy subjects were analyzed to test the efficacy of method. The results show almost identical clusters when applied to different runs of a dataset or to different datasets, indicating a stable performance of our framework. Conclusions and Significance: Our framework provided a novel measure for functional segregation of the brain according to time-frequency characteristics of resting state BOLD activities.


Structural and serological characterisation of the O-antigenic polysaccharide of the lipopolysaccharide from Acinetobacter strain 90 belonging to DNA group 10.
Water-soluble lipopolysaccharide (phenol/water extraction) isolated from Acinetobacter strain 90, which belongs to DNA group 10, was hydrolysed with 1% acetic acid, ultracentrifuged, and water-soluble products finally eluted from a Sephadex G-50 column. The major fraction, a polysaccharide, contained D-Gal, D-GlcNAc, D-GalNAc, and 4,6-dideoxy-4-[(R)-3-hydroxybutyramido]-D-galactose (Fuc4NBuOH). The polysaccharide was characterised by means of monosaccharide analyses, Smith-degradation, N-deacetylation/deamination, and NMR studies, and was shown to have a branched pentasaccharide repeating unit. [structure in text] This structure was specifically recognised in western blots and enzyme immunoassays by polyclonal rabbit antisera.


Rhinorrhea and pneumocephalus after cerebrospinal fluid shunting. The role of lateral extensions of the sphenoid sinus.
Pneumocephalus is usually seen after trauma or neurologic surgery. A rare presentation is after cerebrospinal fluid (CSF) shunting for rhinorrhea. This may be a manifestation of shunt malfunction or of the failure to close a preexisting fistulous tract. A common site of failure is the sphenoid sinus, where CSF may leak from a dehiscence in the middle cranial fossa floor. These dehiscences often communicate with lateral extensions of the sphenoid. This complication is best managed by craniotomy with direct inspection of the floor of the middle cranial fossa and correction of deranged CSF dynamics.


Gene transfer of inducible nitric oxide synthase complementary DNA regresses the fibrotic plaque in an animal model of Peyronie's disease.
The goal of the present study was to investigate the antifibrotic role of inducible nitric oxide synthase (iNOS) in Peyronie's disease (PD) by determining whether a plasmid expressing iNOS (piNOS) injected into a PD-like plaque can induce regression of the plaque. A PD-like plaque was induced with fibrin in the penile tunica albuginea of mice and then injected with a luciferase-expressing plasmid (pLuc), either alone or with piNOS, following luciferase expression in vivo by bioluminescence imaging. Rats were treated with either piNOS, an empty control plasmid (pC), or saline. Other groups were treated with pC or piNOS, in the absence of fibrin. Tissue sections were stained for collagen, transforming growth factor (TGF) beta1, and plasminogen-activator inhibitor (PAI-1) as profibrotic factors; copper-zinc superoxide dismutase (CuZn SOD) as scavenger of reactive oxygen species (ROS); and nitrotyrosine to detect nitric oxide reaction with ROS. Quantitative image analysis was applied. Both iNOS and xanthine oxido-reductase (XOR; oxidative stress) were estimated by Western blot analysis. Luciferase reporter expression was restricted to the penis, peaked at 3 days after injection, but continued for at least 3 wk. In rats receiving piNOS, iNOS expression also peaked at 3 days, but expression decreased at the end of treatment, when a considerable reduction of plaque size occurred. Protein nitrotyrosine, XOR, and CuZn SOD increased, and TGFbeta1 and PAI-1 decreased. The piNOS gene transfer regressed the PD plaque and expression of profibrotic factors, supporting the view that endogenous iNOS induction in PD is defense mechanism by the tissue against fibrosis.


Re-assessing the role of culture on the visual orientation perception of the rod and frame test.
In recent research of culture and ethnicity in visual perception, some researchers have found support for the hypothesis that more collectivistic cultures tend to be more influenced by surrounding contextual visual information than more individualistic cultures. This hypothesis suggests that even low-level visual perception may not be universal and has great implications on how vision research should be conducted. The current study reexamines this hypothesis in the rod and frame task, which tests the influence of a tilted contextual frame on orientation perception of the rod. We found no difference between participants of East Asian and Western European descent in this task. Despite not finding the cultural effect, we found a well-reported gender effect in which women were more influenced by the tilt of the frame than men, helping to ensure the quality of the data collected. Our results suggest that contextual influence on visual perception does not affect East Asians and white Western Europeans differently.


Human Parechovirus Meningitis with Adverse Neurodevelopmental Outcome: A Case Report.
Human parechovirus infections usually cause mild symptoms in children. Although their contribution to severe disease in young children-such as neonatal sepsis and meningoencephalitis-is increasingly recognized, data on long-term consequences are scarce. Here we present the case of a 5-year-old boy with severe long-term neurodevelopmental sequelae after human parechovirus-3 meningitis.


The Importance of H in Particulate Organic Matter Stoichiometry, Export and Energy Flow.
The discipline of marine ecological stoichiometry has progressed rapidly over the past two decades, and continues to be at the forefront of microbial oceanography. Most of this effort has been focused on the elements carbon (C) and nitrogen (N), and to a lesser extent phosphorus (P), with little consideration of hydrogen (H), or the redox state of the organic matter pools despite the fact that H is the most abundant, and possibly the most important, element in biogeochemistry. Obtaining accurate estimates of the H content of organic matter, either in suspended or sinking particles, is a major analytical challenge. While many aquatic science laboratories have access to commercial "C-H-N elemental analyzers," few investigators report H values due to analytical difficulties in obtaining accurate estimates of H. Because organic compounds vary considerably in their H:C ratio and therefore in their energy content, measurements of H combined with C-specific caloric estimates will ultimately be required for a more comprehensive understanding of ecosystem dynamics.


Regiodivergent synthesis of sulfone-tethered lactam-lactones bearing four contiguous stereocenters.
Sulfone-tethered lactones/amides/amines display a diverse spectrum of biological activities, including anti-psychotic and anti-hypertensive. Sulfones are also widely present in functional materials and fragrances. We therefore reasoned that a regiodivergent and stereocontrolled strategy that merges the sulfone, lactone, and lactam motifs would likely lead to the discovery of new pharmacophores and functional materials. Here, we report mild conditions for the sulfonyllactonization of γ-lactam-tethered 5-aryl-4(E)-pentenoic acids. The annulation is highly modular, chemoselective, and diastereoselective. With respect to regioselectivity, trisubstituted alkenoic acids display a preference for 5-exo-trig cyclization whereas disubstituted alkenoic acids undergo exclusive 6-endo-trig cyclization. The lactam-fused sulfonyllactones bear angular quaternary as well as four contiguous stereocenters. The products are post-modifiable, especially through a newly developed Co-catalyzed reductive cross-coupling protocol.


Towards MRI microarrays.
Superparamagnetic iron oxide nanometre scale particles have been utilised as contrast agents to image staked target binding oligonucleotide arrays using MRI to correlate the signal intensity and T(2)* relaxation times in different NMR fluids.


Accurate and precise isotope dilution mass spectrometry method for determining glucose in whole blood.
An accurate and precise method to determine glucose concentration in whole blood is presented. The method, based on isotope dilution gas chromatography-mass spectrometry (ID GC-MS), was developed to be used as a Reference Method for determining glucose concentration in capillary or venous whole blood. Blood samples and standards are pipetted manually with "microcap" micropipettes, which makes it possible to collect samples even at the patient's bedside. Glucose is quantified as its aldononitrile pentaacetate. [13C6]Glucose is used as an internal standard. Assay of Seronorm and Pathonorm L and H controls by ID GC-MS gave within-run CVs of 0.66%, 0.96%, and 0.92%, respectively. For whole blood with glucose concentrations in the low, normal, and high ranges, the within-run CVs were 1.27%, 0.91%, and 0.78%, respectively. The between-run CV for glucose calculated from 36 separate single analyses of Seronorm was 1.44%. In an accuracy assessment test of the HemoCue blood glucose analyzer, 140 capillary blood samples were measured in parallel after split-sampling. For all samples the HemoCue analyzer results had a mean bias of +2.0% compared with the ID GC-MS results.


YOUPI: Your powerful and intelligent tool for segmenting cells from imaging mass cytometry data.
The recent emergence of imaging mass cytometry technology has led to the generation of an increasing amount of high-dimensional data and, with it, the need for suitable performant bioinformatics tools dedicated to specific multiparametric studies. The first and most important step in treating the acquired images is the ability to perform highly efficient cell segmentation for subsequent analyses. In this context, we developed YOUPI (Your Powerful and Intelligent tool) software. It combines advanced segmentation techniques based on deep learning algorithms with a friendly graphical user interface for non-bioinformatics users. In this article, we present the segmentation algorithm developed for YOUPI. We have set a benchmark with mathematics-based segmentation approaches to estimate its robustness in segmenting different tissue biopsies.


Co-Occurrence of NDM-9 and MCR-1 in a Human Gut Colonized Escherichia coli ST1011.
The emergence of the plasmid-borne colistin-resistant gene (mcr-1) poses a great threat to human health. What is worse, the recent observations of the coexistence of mcr-1 with carbapenemase encoding genes in some bacteria caused even more concern. Yet, there is a lack of observations of such strains in the human gut. The isolation of E. coli L889 was performed on selective medium plates. Antibiotic susceptibilities were determined by an agar dilution and a broth microdilution method. Multi-locus sequence typing (MLST) and acquired resistance genes were also characterized. Transferability of bla NDM-9/mcr-1-carrying plasmids was determined by conjugation, replicon typing and S1-Pulsed-field gel electrophoresis (S1-PFGE), and Southern blotting. The sequences of these plasmids were analyzed by using whole-genome sequencing with Illumina Novaseq and Nanopore platforms. E. coli L889 was identified as ST1101 concomitantly carrying bla NDM-9 and mcr-1 from a stool sample. Antimicrobial susceptibility tests showed that it was resistant to various antimicrobial agents and only susceptible to tigecycline. Notably, bla NDM-9 was located on a ~114-kb untypable plasmid, while mcr-1 was located on a ~63-kb IncI2 plasmid. Our research, to our knowledge, first reported an ST1101 E. coli strain with an untypeable bla NDM-9-harbouring plasmid and an IncI2 mcr-1-carrying plasmid. The colonized E. coli strains potentially contribute to the dissemination and transfer of bla NDM-9 and mcr-1 to clinical isolates, which is a considerable threat to public health and should be closely monitored.


Dysregulation of cytokine expression in tubulointerstitial nephritis associated with murine malaria.
We examined the circulating levels of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 alpha, IL-6, granulocyte macrophage-colony stimulating factor (GM-CSF), and the anti-inflammatory cytokine IL-10, and their expression in kidneys acutely infected with murine malaria parasite P. berghei ANKA in C57BL/6J mice. Groups of six mice sacrificed on days 5, 10, 15, and 20, and normal controls were used for cytokine analysis. High concentrations of TNF-alpha and IL-10 were detected in plasma as shown by ELISA, and elevated levels of mRNA specific for TNF-alpha and IL-10 in infected kidneys were demonstrated by reverse transcription-polymerase chain reaction (RT-PCR) analysis. Kidney sections stained with antibodies against TNF-alpha, IL-1 alpha, IL-6, GM-CSF and IL-10 for immunohistochemistry showed markedly enhanced staining for TNF-alpha, and progressively increased staining for IL-1 alpha and IL-6 both in the tubules and the walls of arteries during the course of infection. The endothelia of blood vessels and inflammatory cells located around small arteries showed positive staining for GM-CSF from day 10 onwards. Unlike the staining for proinflammatory cytokines, the anti-inflammatory cytokine IL-10 showed strongly positive staining in normal tubules and walls of arteries, especially in the brush border of proximal tubules, but the staining intensity decreased dramatically after day 15 post-infection. A strongly positive correlation was found between the antibody staining for TNF-alpha/IL-1 alpha in tubules, and the severity of proteinuria. In contrast, there was an inverse correlation between the staining for IL-10 with TNF-alpha/IL-1 alpha, and the degree of proteinuria. Plenty of pigmented macrophages showed positive staining both for proinflammatory and anti-inflammatory cytokines in the tubulointerstitium. Our findings imply that the up-regulation of proinflammatory cytokines and the dysregulation of anti-inflammatory cytokines are involved in the pathogenesis of tubulointerstitial nephritis associated with malaria.


Increased number of mast cells in the dermis in actinic keratosis lesions effectively treated with imiquimod.
Actinic keratosis (AK) is a cutaneous cancer in situ which develops as a result of excessive exposure to ultraviolet (UV). Toll-like receptor (TLR)7 agonist imiquimod is a topical immune response modifier and is effective for the treatment of non-melanoma skin cancers. Recently, the diagnostic role of the dermatoscope has been reported in the course of treatment of AK. In addition, mast cells are now considered to contribute to both the innate and adaptive immune systems in topical imiquimod therapy. We assessed the effect of imiquimod treatment by dermatoscopic and immunohistochemical findings in 14 patients with a total of 21 AK lesions. With the dermatoscope, though the mean erythema score was not significantly different between the cured lesions and the unresponsive lesions, the erythema/red pseudo-network ("strawberry") pattern was decreased significantly in the cured lesions. By immunohistochemistry, the number of Ki-67-positive proliferative cells in the epidermis was decreased and that of CD117-positive mast cells in the dermis was increased in the responding lesions. To the best of our knowledge, this is the first study demonstrating that the number of mast cells in the dermis was increased in AK lesions effectively treated with imiquimod. Our present result suggests that mast cells may contribute an antitumor effect in human skin treated with topical imiquimod.


N₂ gas plasma inactivates influenza virus mediated by oxidative stress.
Here we show that N₂ gas plasma, produced by applying a short high-voltage pulse using a static induction (SI) thyristor power supply inactivates influenza virus. N₂ gas plasma treatment of influenza A and B viruses induced the degradation of viral proteins, including nucleoprotein, hemagglutinin, and neuraminidase. The injury of viral RNA genome and the inactivation of hemagglutination were also observed after N₂ gas plasma treatment. These changes were possibly due to changes in the viral envelope, because modification of the lipid content was also suggested by Fourier-transformed infrared spectroscopy. At least three major mechanisms of action (heat, UV-A, and oxidative stress (i.e. hydrogen peroxide-like molecules)) were found in this system. Among them, oxidative stress appeared to be the main factor in the inactivation of influenza virus. In addition, there was an increase in the nitrotyrosine content of viral proteins, suggesting that oxidative stress produced by N₂ gas plasma generation oxidized proteins. As a result, oxidation may be the most important factor in the inactivation, degradation, and modification of influenza virus by N₂ gas plasma.


Enhancing the electron transfer capacity and subsequent color removal in bioreactors by applying thermophilic anaerobic treatment and redox mediators.
The effect of temperature, hydraulic retention time (HRT) and the redox mediator anthraquinone-2,6-disulfonate (AQDS), on electron transfer and subsequent color removal from textile wastewater was assessed in mesophilic and thermophilic anaerobic bioreactors. The results clearly show that compared with mesophilic anaerobic treatment, thermophilic treatment at 55 degrees C is an effective approach for increasing the electron transfer capacity in bioreactors, and thus improving the decolorization rates. Furthermore, similar color removals were found at 55 degrees C between the AQDS-free and AQDS-supplemented reactors, whereas a significant difference (up to 3.6-fold) on decolorization rates occurred at 30 degrees C. For instance, at an HRT of 2.5 h and in the absence of AQDS, the color removal was 5.3-fold higher at 55 degrees C compared with 30 degrees C. The impact of a mix of mediators with different redox potentials on the decolorization rate was investigated with both industrial textile wastewater and the azo dye Reactive Red 2 (RR2). Color removal of RR2 in the presence of anthraquinone-2-sulfonate (AQS) (standard redox potential E(0)' of -225 mV) was 3.8-fold and 2.3-fold higher at 30 degrees C and 55 degrees C, respectively, than the values found in the absence of AQS. Furthermore, when the mediators 1,4-benzoquinone (BQ) (E(0)' of +280 mV), and AQS were incubated together, there was no improvement on the decolorization rates compared with the bottles solely supplemented with AQS. Results imply that the use of mixed redox mediators with positive and negative E(0)' under anaerobic conditions is not an efficient approach to improve color removal in textile wastewaters.


Environment-Adaptive Coassembly/Self-Sorting and Stimulus-Responsiveness Transfer Based on Cholesterol Building Blocks.
Manipulating the property transfer in nanosystems is a challenging task since it requires switchable molecular packing such as separate aggregation (self-sorting) or synergistic aggregation (coassembly). Herein, a unique manipulation of self-sorting/coassembly aggregation and the observation of switchable stimulus-responsiveness transfer in a two component self-assembly system are reported. Two building blocks bearing the same cholesterol group give versatile topological structures in polar and nonpolar solvents. One building block (cholesterol conjugated cynanostilbene, CCS) consists of cholesterol conjugated with a cynanostilbene unit, and the other one (C10CN) is comprised of cholesterol connected with a naphthalimide group having a flexible long alkyl chain. Their assemblies including gel, crystalline plates, and vesicles are obtained. In gel and crystalline plate phases, the self-sorting behavior dominates, while synergistic coassembly occurs in vesicle phase. Since CCS having the cyanostilbene group can respond to the light irradiation, it undergoes light-induced chiral amplification. C10CN is thermally responsive, whereby its supramolecular chirality is inversed upon heating. In coassembled vesicles, it is interestingly observed that their responsiveness can be transferred by each other, i.e., the C10CN segment is sensitive to the light irradiation, while CCS is thermoresponsive. This unprecedented behavior of the property transfer may shine a light to the precise fabrication of smart materials.


Redesign of a Pyrylium Photoredox Catalyst and Its Application to the Generation of Carbonyl Ylides.
We report the exploration into photoredox generation of carbonyl ylides from benzylic epoxides using newly designed 4-mesityl-2,6-diphenylpyrylium tetrafluoroborate (MDPT) and 4-mesityl-2,6-di-p-tolylpyrylium tetrafluoroborate (MD(p-tolyl)PT) catalysts. These catalysts are excited at visible wavelengths, are highly robust, and exhibit some of the highest oxidation potentials reported. Their utility was demonstrated in the mild and efficient generation of carbonyl ylides from benzylic epoxides that otherwise could not be carried out by current common photoredox catalysts.


Low-light imaging technology in the life sciences.
Photon imaging is an increasingly important technique for the measurement and analysis of chemiluminescence and bioluminescence. New high-performance low-light level imaging systems have recently become available for the life sciences. These systems use advances in camcera design and digital image processing and are now being used for a wide range of luminescence applications. They offer good sensitivity for photon detection and large dynamic range, and are suitable for quantitative analysis. This is achieved using a range of software techniques including image arithmetic, histogramming or summing regions of interest, feature extraction and multiple image processing for kinetics or assay screening. Improvements in image-processing hardware and software have increased the usefulness of these systems in the biosciences. Low-light imaging is a rapid and non-invasive method for the sensitive detection and analysis of luminescent assays. As such it offers a powerful and sensitive tool for investigating processes, both at the cellular level (luc and lux reporter genes, intracellular signalling) and for measurement of macro samples (immunoassays, gels and blots, tissue sections).


Single-Cell-Arrayed Agarose Chip for in Situ Analysis of Cytotoxicity and Genotoxicity of DNA Cross-Linking Agents.
Development of approach or device to allow continuous multiple measurements, such as integrating cytotoxic and genotoxic analysis, is quite appealing for study of the drug's activity and mechanism of action or resistance. In this study, a single-cell-arrayed agarose chip system was developed to combine cell cultivation with subsequent in situ analysis of cytotoxicity and genotoxicity of the chemotherapeutic agent. The modified alkaline comet assay coupled with the Live/Dead assay was used to monitor the interstrand cross-links (ICLs) formation and the cytotoxic effects in different glioma cell lines. In addition, the ICL-induced double strand breaks (DSBs) was measured on the chip to reflect the level of ICLs indirectly. Compared with the traditional methods, the microarray agarose device offers higher throughput, reproducibility, and robustness, exhibiting good potential for high-content drug screening.


Characterisation of a soft elastomer poly(glycerol sebacate) designed to match the mechanical properties of myocardial tissue.
The myocardial tissue lacks significant intrinsic regenerative capability to replace the lost cells. Therefore, the heart is a major target of research within the field of tissue engineering, which aims to replace infarcted myocardium and enhance cardiac function. The primary objective of this work was to develop a biocompatible, degradable and superelastic heart patch from poly(glycerol sebacate) (PGS). PGS was synthesised at 110, 120 and 130 degrees C by polycondensation of glycerol and sebacic acid with a mole ratio of 1:1. The investigation was focused on the mechanical and biodegrading behaviours of the developed PGS. PGS materials synthesised at 110, 120 and 130 degrees C have Young's moduli of 0.056, 0.22 and 1.2 MPa, respectively, which satisfy the mechanical requirements on the materials applied for the heart patch and 3D myocardial tissue engineering construction. Degradation assessment in phosphate buffered saline and Knockout DMEM culture medium has demonstrated that the PGS has a wide range of degradability, from being degradable in a couple of weeks to being nearly inert. The matching of physical characteristics to those of the heart, the ability to fine tune degradation rates in biologically relevant media and initial data showing biocompatibility indicate that this material has promise for cardiac tissue engineering applications.


In vitro and in vivo metabolism of a potent and selective integrin alpha v beta 3 antagonist in rats, dogs, and monkeys.
Compound A (3-[2-oxo-3-[3-(5,6,7,8-tetrahydro-[1,8]naphthyrindin-2-yl)propyl]-imidazolidin-1-yl]-3(S)-(6-methoxy-pyridin-3-yl)-propionic acid), a potent and selective antagonist of integrin alpha(v)beta(3) receptor, is under development for treatment of osteoporosis. This study describes metabolism and excretion of A in vivo in rats, dogs, and monkeys, and metabolism of A in vitro in primary hepatocytes from rats, dogs, monkeys, and humans. In all three animal species studied, A was primarily excreted as unchanged drug and, to a lesser degree, as phase I and phase II metabolites. Major biotransformation pathways of A included glucuronidation/glucosylation on the carboxylic group to form acyl-linked glucuronides/glucosides; and oxidation on the tetrahydronaphthyridine moiety to generate a carbinolamine and its further metabolized products. Minor pathways involved O-demethylation and hydroxylations on the alkyl chain. Only in rats, a glutathione adduct of A was also observed, and its formation is proposed to be via an iminium intermediate on the tetrahydronaphthyridine ring. Similar metabolic pathways were observed in the incubates of hepatocytes from the corresponding animals as well as from humans. CYP 3A and 2D subfamilies were capable of metabolizing A to its oxidative products. Overall, these in vitro and in vivo findings should provide useful insight on possible biotransformation pathways of A in humans.


Sex differences in the associations of HIV disease characteristics and body composition in antiretroviral-naive persons.
Data on associations of body composition with HIV disease characteristics are limited. We compared sex-specific associations between HIV disease characteristics and body composition in an racially-ethnically diverse cohort of antiretroviral-naive patients. The study was a cross-sectional analysis of participants enrolled in a metabolic substudy of a multicenter trial. Regional fat was measured, and total body fat (TBF) was derived by using the Durnin-Womersley formula (DWF) and bioelectrical impedance analysis (BIA). Body cell mass (BCM) was measured by BIA. Among 422 participants, 22% were women, 60% were African American, and 36% had prior AIDS-defining illnesses. Mean (+/-SD) age was 38.2 +/- 9.6 y, CD4+ count was 215 +/- 184 cells/mm3, and HIV RNA log10 was 5.0 +/- 0.8 copies/mL. On multivariate analysis, women with AIDS-defining illness had significantly (P < 0.005) lower regional body fat and TBF (BIA: -9.5 kg; DWF: -7.3 kg) but nonsignificantly lower BCM (-1.3 kg) than did women without such illnesses, whereas men with AIDS-defining illness had significantly (P < 0.005) lower BCM (-1.7 kg) but nonsignificantly lower TBF (BIA: -1.3 kg; DWF: -1.83 kg) than did men without such illnesses (P < 0.05 for sex differences in TBF). Significant negative associations of HIV RNA with BCM (-0.9 kg/log RNA; P = 0.03), TBF by BIA (-1.4 kg/log RNA; P = 0.05) and by DWF (-1.6 kg/log RNA; P = 0.01), and regional fat were observed in men only. The effect of prior AIDS illness on body fat differed significantly between the sexes: women with prior AIDS-defining illness had significantly less fat than did women without such illnesses. An independent effect of HIV viremia on BCM and fat was seen in men. These distinctions may be due to inherent biological differences between the sexes.


Distribution of linear antigenic sites on glycoprotein gp55 of human cytomegalovirus.
Human convalescent serum and bacterial fusion proteins constructed from overlapping open reading frames of the nucleotide sequence encoding the human cytomegalovirus gp55 component of the major envelope glycoprotein complex, gp55-116 (gB), were used to localize antigenic regions recognized by human antibodies. All donor serum analyzed contained antibody reactivity for an antigenic site(s) located between amino acids (AA) 589 and 645, a region containing a previously defined linear site recognized by neutralizing monoclonal antibodies (U. Utz, B. Britt, L. Vugler, and M. Mach, J. Virol. 63:1995-2001, 1989). Furthermore, in-frame insertion of two different synthetic oligonucleotides encoding four amino acids into the sequence at nucleotide 1847 (AA 616) eliminated antibody recognition of the fusion protein. A second antibody binding site was located within the carboxyl terminus of the protein (AA 703 through 906). A competitive binding inhibition assay in which monoclonal antibodies were used to inhibit human antibody reactivity with recombinant gp55-116 (gB) suggested that the majority of human anti-gp55-116 (gB) antibodies were directed against a single antigenic region located between AA 589 and 645. Furthermore, inoculation of mice with fusion proteins containing this antigenic site led to a boostable antibody response. These results indicated that the antigenic site(s) located between AA 589 and 645 was an immunodominant antibody recognition site on gp55 and likely the whole gp55-116 (gB) molecule. The enhanced immunogenicity of this region in vivo may account for its immunodominance.


The emergence of international comparisons of health inequalities as reflected in the Scandinavian Journal of Public Health during its five decades.
We examined the development of research articles published in the Scandinavian Journal of Public Health and its predecessors Acta Socio-Medica Scandinavica and the Scandinavian Journal of Social Medicine from 1969 until 2020 to be able to identify the place of international comparisons of socioeconomic inequalities in health in the journal. Altogether 3237 research articles were screened to yield 126 comparative research articles. Examining full texts of the comparative articles led to 13 articles reporting comparisons of health inequalities. The first one came out in 1972, but the rest only after the mid-1990s. The most common socioeconomic indicator was education, but also occupational class and income was used. The most common health indicator was self-rated health. The articles compared Nordic countries with each other, but also with non-Nordic countries. Although the number of comparative studies on health inequalities was relatively small, there were examples of well-designed studies using advanced methodology. We examined only published journal articles over the past five decades, not submitted but rejected papers. In the Scandinavian Journal of Public Health and its predecessors, comparisons of health inequalities were few and emerged relatively late, that is, during the past two decades.


Pre-pregnancy body mass index and glycated-hemoglobin with the risk of metabolic diseases in gestational diabetes: a prospective cohort study.
Metabolic diseases during pregnancy result in negative consequences for mothers. Pre-pregnancy body mass index (BMI) and late-pregnancy glycated-hemoglobin (HbA1c) are most important factors independently affecting the risk of gestational diabetes mellitus (GDM). However how both affect the combined risk of other metabolic diseases in women with GDM is unclear. The study aims to investigate the influence of pre-pregnancy BMI and pregnancy glycemic levels on other gestational metabolic diseases in women with GDM. Pregnancies with GDM from January 2015 to December 2018 in the Xi'an longitudinal mother-child cohort study (XAMC) were retrospectively enrolled. Those without other metabolic diseases by the time of oral glucose tolerance test (OGTT) detection were finally recruited and divided into four groups by pre-pregnancy BMI (Underweight <18.5kg/m2; Normal weight 18.5-23.9 kg/m2; Overweight 24.0-27.9 kg/m2; Obesity ≥28.0 kg/m2, respectively) or two groups by HbA1c in late pregnancy (normal HbA1c<5.7%; high HbA1c≥5.7%). Multivariate logistic regression analysis was used to identify risk factors. Interaction between pre-pregnancy BMI (reference group 18.5-23.9 kg/m2) and HbA1c (reference group <5.7%) was determined using strata-specific analysis. A total of 8928 subjects with GDM were included, 16.2% of which had a composite of metabolic diseases. The pre-pregnancy overweight and obesity, compared with normal BMI, were linked to the elevated risk of the composite of metabolic diseases, particularly pre-eclampsia (both P <0.001) and gestational hypertension (both P <0.001). Meanwhile, patients with high HbA1c had an obvious higher risk of pre-eclampsia (P< 0.001) and gestational hypertension (P= 0.005) compared to those with normal HbA1c. In addition, there were significant interactions between pre-pregnancy BMI and HbA1c (P< 0.001). The OR of pre-pregnancy BMI≥ 28 kg/m2 and HbA1c≥ 5.7% was 4.46 (95% CI: 2.85, 6.99; P< 0.001). The risk of other metabolic diseases, except for pre-eclampsia (P= 0.003), was comparable between the two groups of patients with different HbA1c levels at normal pre-pregnancy BMI group. However, that was remarkably elevated in obese patients (P= 0.004), particularly the risk of gestational hypertension (P= 0.004). Pre-pregnancy overweight/obesity and late-pregnancy high HbA1c increased the risk of other gestational metabolic diseases of women with GDM. Monitoring and controlling late-pregnancy HbA1c was effective in reducing metabolic diseases, particularly in those who were overweight/obese before conception.


Production of biomolecules of interest to the anxiolytic herbal medicine industry in yellow passionfruit leaves (Passiflora edulis f. flavicarpa) promoted by mycorrhizal inoculation.
Our contemporary way of life has led us to consume high amounts of chemically-synthesized allopathic medicinal products and anxiolytics to which a viable alternative is the use of Passiflora-based herbal medicines with composition containing vitexin, a flavonoid with anxiolytic and antidepressant properties. Arbuscular mycorrhizal fungi (AMF) are known for enhancing the production of biomolecules, however, increase production of phytochemistry in Passiflora edulis f. flavicarpa has not been reported in the literature. Our aim was to select AMF to benefit the production of vitexin in leaves of P. edulis by inoculating seedlings in the region of roots with Acaulospora longula, Claroideoglomus etunicatum and Gigaspora albida. The inoculation increased the concentration of vitexin in 63.64% and the inoculation with A. longula also increased the content of flavonoids and total saponins in the leaves in relation to the control. The increase in the production of vitexin in the leaf in response to the inoculation with AMF, with emphasis to A. longula, interests the pharmaceutical industry and can generate profit to the production of yellow passionfruit-based anxiolytic herbal medicine. © 2019 Society of Chemical Industry.


Repeated measurement sampling in genetic association analysis with genotyping errors.
Genotype misclassification occurs frequently in human genetic association studies. When cases and controls are subject to the same misclassification model, Pearson's chi-square test has the correct type I error but may lose power. Most current methods adjusting for genotyping errors assume that the misclassification model is known a priori or can be assessed by a gold standard instrument. But in practical applications, the misclassification probabilities may not be completely known or the gold standard method can be too costly to be available. The repeated measurement design provides an alternative approach for identifying misclassification probabilities. With this design, a proportion of the subjects are measured repeatedly (five or more repeats) for the genotypes when the error model is completely unknown. We investigate the applications of the repeated measurement method in genetic association analysis. Cost-effectiveness study shows that if the phenotyping-to-genotyping cost ratio or the misclassification rates are relatively large, the repeat sampling can gain power over the regular case-control design. We also show that the power gain is not sensitive to the genetic model, genetic relative risk and the population high-risk allele frequency, all of which are typically important ingredients in association studies. An important implication of this result is that whatever the genetic factors are, the repeated measurement method can be applied if the genotyping errors must be accounted for or the phenotyping cost is high.


Prediction of early progression in recently diagnosed IgA nephropathy.
Most studies of prognosis in IgA nephropathy (IgAN) have tried to predict dichotomous outcomes based on a small number of clinical or semi-quantitative histological variables in large numbers of patients. We pursued a quite different approach. We measured GFR annually for 4-5 years in 22 adult patients with recently diagnosed IgAN. Quantitative morphology was performed on the diagnostic biopsy specimens and baseline glomerular filtration dynamics were performed at study entry. An initial set of 30 plausible predictor variables (half demographic or physiological, half structural) was reduced to 22 using phylogenetic trees. Least-angle regression (LARS) was used to predict the rate of GFR change from these variables The rate of GFR change ranged from a loss of 41 ml/min/year to a gain of 8.6 ml/min/year. We found an optimum predictor set of five baseline variables: the percentage of glomeruli with global sclerosis, the fractional interstitial area, the serum creatinine, the average tuft volume of non-sclerotic glomeruli and the renal plasma flow. The strong predictive relationship of the three structural variables with the slope of GFR in our subjects suggests that even at the time of their initial diagnosis many patients with IgAN already manifest a 'remnant kidney' phenomenon. The distinctive pathophysiological insights derived from this study suggest some of the advantages of intense quantitative investigations applied to a small number of subjects.


Idiopathic multiple eruptive milia occurred in unusual sites.
Milia are small, white, benign keratinous cysts that are frequently encountered. Multiple eruptive milia are rare, and are characterized by the development of milia that are more extensive in number and distribution than would be expected in primary milia. We report a case of a 19-year-old girl with tiny, white papules in her axillae and on her abdomen with a review of the relevant literature.


Transfer Entropy as a Measure of Brain Connectivity: A Critical Analysis With the Help of Neural Mass Models.
Objective: Assessing brain connectivity from electrophysiological signals is of great relevance in neuroscience, but results are still debated and depend crucially on how connectivity is defined and on mathematical instruments utilized. Aim of this work is to assess the capacity of bivariate Transfer Entropy (TE) to evaluate connectivity, using data generated from simple neural mass models of connected Regions of Interest (ROIs). Approach: Signals simulating mean field potentials were generated assuming two, three or four ROIs, connected via excitatory or by-synaptic inhibitory links. We investigated whether the presence of a statistically significant connection can be detected and if connection strength can be quantified. Main Results: Results suggest that TE can reliably estimate the strength of connectivity if neural populations work in their linear regions, and if the epoch lengths are longer than 10 s. In case of multivariate networks, some spurious connections can emerge (i.e., a statistically significant TE even in the absence of a true connection); however, quite a good correlation between TE and synaptic strength is still preserved. Moreover, TE appears more robust for distal regions (longer delays) compared with proximal regions (smaller delays): an approximate a priori knowledge on this delay can improve the procedure. Finally, non-linear phenomena affect the assessment of connectivity, since they may significantly reduce TE estimation: information transmission between two ROIs may be weak, due to non-linear phenomena, even if a strong causal connection is present. Significance: Changes in functional connectivity during different tasks or brain conditions, might not always reflect a true change in the connecting network, but rather a change in information transmission. A limitation of the work is the use of bivariate TE. In perspective, the use of multivariate TE can improve estimation and reduce some of the problems encountered in the present study.


From "exfoliative" to "diagnostic" cytology. A statistical evaluation of pulmonary cytology.
During the year 1975, a total of 2,877 cytologic examinations in our laboratory included 2,277 examinations on 580 patients related to pulmonary cytology. Statistical evaluation of these studies indicates that the present trend of pulmonary cytology examination is moving from "exfoliative" cytology to "diagnostic" cytology. As long as one maintains the specificity of the examination high enough by the application of stringent criteria for cytodiagnosis, further radio and/or chemotherapy can be justifiably instituted on the basis of cytologic examination along with clinical evaluation of the patients when histopathologic diagnosis is not obtainable.


The impact of diabetes on the association between epicardial fat thickness and extent and complexity of coronary artery disease in patients with non-ST elevation myocardial infarction.
Epicardial fat thickness (EFT) is associated with increased cardio metabolic risk. Recent studies have suggested that there is a strong relationship between diabetes and EFT. Although the relationship between EFT and coronary artery disease (CAD) is well known, the possible impact of diabetes on the relationship between EFT and extent and complexity of CAD was not fully investigated. We aimed to investigate the relationship between EFT and extent and complexity of CAD in patients with non-ST elevation myocardial infarction (NSTEMI) with and without diabetes. We prospectively included 454 patients with NSTEMI (mean age: 61.8 ± 10.4 years) in the present study. Patients were classified into two groups according to their diabetes status (diabetic group and non-diabetic group). EFT was measured by transthoracic echocardiography on the right ventricle in individuals having the left lateral decubitus position. SYNTAX score was used to define the extent and complexity of CAD. High-sensitivity C-reactive protein (hs-CRP) and other biochemical markers were measured in all participants. Diabetic patients had higher EFT values compared with non-diabetics (p < 0.05). EFT is independently associated with diabetes, SYNTAX score, and hs-CRP in all patients (p < 0.05, for all). When patients were divided into two groups, as diabetic and non-diabetic, the association between EFT and SYNTAX score was stronger in diabetic patients compared with non-diabetics (r = 0.635; p < 0.001 vs. r = 0.179; p = 0.003). Epicardial fat thickness is associated with SYNTAX score in both diabetic and non-diabetic patients. Furthermore, there is a stricter relationship between EFT and SYNTAX score in diabetic patients.


Czy smog ma wpływ na częstość występowania zaostrzeń przewlekłego zapalenia krtani? Analiza na przykładzie mieszkańców województwa małopolskiego.
Due to dynamic industrialisation smog became a frequent phenomenon in most developing cities. According to the last WHO report from Global Urban Ambient Air Pollution Database, Krakow has been classified in the 11th place among the most polluted cities in Europe. It seems to be an urgent issue because of the influence of air pollution on the condition of upper respiratory tract. Materials & Methods: In December 2015 there were 141 patients aged 17-91 years with upper respiratory tract diseases admitted to the phoniatric outpatient clinic in the University Hospital in Cracow. They suffered from cough, hoarseness and periodic aphonia. On the basis of the results of videolaryngostroboscopy 60 patients with exacerbation of the chronic laryngitis were selected into two numerically equal groups: from Cracow and from other places at least 60 km away. The groups were equal to each other also in three categories: sex, age and voice usage. The patients were referred to the Pedagogical University in Cracow for laryngography to evaluate the movement of the vocal folds and to trace a voice profile. Finally, there were two possible types of treatment - conventional pharmacotherapy or subterraneotherapy in the underground Health Resort in the "Wieliczka" Salt Mine. Pearson correlation coefficient between the distance from the place of residence to Cracow and the scale of exacerbation of inflammation of upper respiratory tract presenting as vocal fold dysfunction was observed (r= 0,617; p<0,05). The place of residence (in or out of the industrial area) and exacerbations of chronic laryngitis are highly correlated. Air pollution seems to be the main factor influencing on the condition of upper respiratory tract. In our local conditions of Lesser Poland Voivodeship subterraneotherapy may be an interesting, non-invasive method preventing from exacerbations of upper respiratory tract diseases.


Predicting adherence to medications using health psychology theories: a systematic review of 20 years of empirical research.
This review sought to identify the empirical evidence for the application of models from sociocognitive theory, self-regulation theory, and social support theory at predicting patient adherence to medications. A systematic review of the published literature (1990-2010) using MEDLINE, EMBASE, Cochrane Library, CINAHL, and PsychINFO identified studies examining the application of health psychology theory to adherence to medication in adult patients. Two independent reviewers extracted data on medication, indication, study population, adherence measure, theory, model, survey instruments, and results. Heterogeneity in theoretical model specification and empirical investigation precluded a meta-analysis of data. Of 1756 unique records, 67 articles were included (sociocognitive = 35, self-regulation = 21, social support = 11). Adherence was most commonly measured by self-report (50 of 67). Synthesis of studies highlighted the significance (P ≤ 0.05) of self-efficacy (17 of 19), perceived barriers (11 of 17), perceived susceptibility (3 of 6), necessity beliefs (8 of 9), and medication concerns (7 of 8). The results of this review provide a foundation for the development of theory-led adherence-enhancing interventions that could promote sustainable behavior change in clinical practice.