FMAj: a tool for high content analysis of muscle dynamics in Drosophila metamorphosis.
During metamorphosis in Drosophila melanogaster, larval muscles undergo two different developmental fates; one population is removed by cell death, while the other persistent subset undergoes morphological remodeling and survives to adulthood. Thanks to the ability to perform live imaging of muscle development in transparent pupae and the power of genetics, metamorphosis in Drosophila can be used as a model to study the regulation of skeletal muscle mass. However, time-lapse microscopy generates sizeable image data that require new tools for high throughput image analysis. We performed targeted gene perturbation in muscles and acquired 3D time-series images of muscles in metamorphosis using laser scanning confocal microscopy. To quantify the phenotypic effects of gene perturbations, we designed the Fly Muscle Analysis tool (FMAj) which is based on the ImageJ and MySQL frameworks for image processing and data storage, respectively. The image analysis pipeline of FMAj contains three modules. The first module assists in adding annotations to time-lapse datasets, such as genotypes, experimental parameters and temporal reference points, which are used to compare different datasets. The second module performs segmentation and feature extraction of muscle cells and nuclei. Users can provide annotations to the detected objects, such as muscle identities and anatomical information. The third module performs comparative quantitative analysis of muscle phenotypes. We applied our tool to the phenotypic characterization of two atrophy related genes that were silenced by RNA interference. Reduction of Drosophila Tor (Target of Rapamycin) expression resulted in enhanced atrophy compared to control, while inhibition of the autophagy factor Atg9 caused suppression of atrophy and enlarged muscle fibers of abnormal morphology. FMAj enabled us to monitor the progression of atrophic and hypertrophic phenotypes of individual muscles throughout metamorphosis. We designed a new tool to visualize and quantify morphological changes of muscles in time-lapse images of Drosophila metamorphosis. Our in vivo imaging experiments revealed that evolutionarily conserved genes involved in Tor signalling and autophagy, perform similar functions in regulating muscle mass in mammals and Drosophila. Extending our approach to a genome-wide scale has the potential to identify new genes involved in muscle size regulation.


Cystatin C and transthyretin expression in normal and neoplastic tissues of the human brain and pituitary.
The localization of cystatin C (CC) and transthyretin (TTR) synthesis was studied using Northern blot and immunohistochemical methods. Normal brain tissues from all sites studied contained CC mRNA. Immunoreactive CC was present in the choroid plexus epithelial cells, cerebral and cerebellar neurons, astrocytes, ependymal cells, macrophage-like cells of the arachnoid membrane and in neuroendocrine cells of the anterior pituitary lobe. TTR mRNA and TTR were restricted to the choroid plexus. In primary brain tumors, the transcript for CC was found in all 39 tumors examined, while the protein could only be demonstrated in 3/5 choroid plexus papillomas, 8/8 astrocytomas, 7/23 anaplastic astrocytomas and glioblastomas, 1/6 oligodendrogliomas, 1/1 oligoastrocytoma, 1/4 anaplastic oligodendrogliomas, 3/7 ependymomas, 0/1 anaplastic ependymoma, 0/5 primitive neuroectodermal tumors, 0/1 neuroblastoma, 3/11 meningiomas and 16/16 pituitary adenomas. CC cannot be used as a marker for any specific brain tumor type but the fact that the protein could be demonstrated more frequently in astrocytomas than in their more malignant counterparts suggests that the cellular production and secretion of CC changes with the malignant progression of these tumors. TTR mRNA and TTR were present only in the choroid plexus papillomas, indicating that TTR synthesis is mainly restricted to such brain neoplasms.


A multicenter observational safety study in Swedish children and adolescents using insulin detemir for the treatment of type 1 diabetes.
This 26-wk observational study in children and adolescents with type 1 diabetes (T1D) in Sweden investigated the safety and efficacy of insulin detemir (IDet) in newly diagnosed (ND) patients and those with established diabetes (ED) switching to IDet. A total of 159 patients initiated IDet as part of basal-bolus therapy, 59 in the ND stratum (mean age 9.7 yr) and 97 in the ED stratum (mean age 12.5 yr). The primary outcome measure was the incidence of severe adverse drug reactions; just one major hypoglycemic event occurred in a patient in the ND stratum during the study and one patient was withdrawn due to injection-site reactions. All other events were classified as mild. In the ED stratum, there was a reduction in hypoglycemic events in the 4 wk prior to study end from baseline (mean reduction of 2.46 events, not significant) and a significant reduction in nocturnal hypoglycemia (mean reduction of 2.24 events, p = 0.0078). Glycemic control improved in the ND stratum as expected and, in the ED stratum, there was no significant change in HbA1c from baseline (mean reduction of -0.45%). At study end, mean daily IDet doses were 0.39 U/kg (ND) and 0.54 U/kg (ED). Weight increased by 5.7 and 2.0 kg in the ND and ED strata, respectively, and was within the normal limits for growing children. IDet provided good glycemic control and was well tolerated, with a reduced risk of nocturnal hypoglycemia in a heterogeneous cohort of children and adolescents with T1D.


[Effects of hydrogen sulfide on contraction capacity of diaphragm from type 1 diabetic rats].
To investigate the effects of hydrogen sulfide (H2S) on contraction capacity of diaphragm in type 1 diabetic rats. Thirty-two male SD rats were randomly divided into a normal group (NC), a diabetic group (DM), a NaHS treatment group (DM+NaHS) and a NaHS group (NaHS) (n=8). Intraperitoneal injection of streptozotocin was utilized to establish diabetic rat model. After the modeling, the rats in the DM+NaHS and the NaHS groups were intraperitoneally injected with 28 μmol/kg NaHS solution. 8 weeks later, the diaphragm contractility was assessed by isolated draphragm strips perfusion. The peak twitch tension (Pt), maximum tetanic tension (Po) and maximal rates of contraction/relaxation (±dT/dtmax) were determined. The alterations in diaphragm ultrastructure were observed under electron microscopy. The diaphragm weight/body weight (DW/BW) was measured. The activities of succinic dehydrogenase (SDH), lactate dehydrogenase (LDH) and sarcoplasmic reticulum Ca2+ ATPase (SERCA) were analyzed by spectrophotometric method. The mRNA levels of SERCA and prospholamban (PLB) in diaphragm were detected by RT-PCR. Compared with the NC group, there was no significant change in all measured index in the NaHS group (P>0.05), while Pt, Po and ±dT/dtmax were significantly decreased in the DM group (P<0.05). Transmission electron microscopy revealed obvious ultrastructural changes in the diaphragm. The DW/BW ratio and the activities of SDH, LDH and SERCA were decreased. The SERCA mRNA was decreased, while PLB mRNA was increased. Compared with the DM group, the diaphragm contractility and ultrastructure damage were improved in the DM+NaHS group. The DW/BW ratio and the activities of SDH, LDH and SERCA were increased. The SERCA mRNA was increased, while PLB mRNA was decreased (all P<0.05). H(2)S can enhance the contraction capacity of diaphragm in type 1 diabetic rats, which is involved in regulating the activities of biological enzymes and the gene expressions of calcium regulatory proteins.


Programming eccentricities of an activity sensing pacemaker.
The Activitrax rate responsive pacemaker system has enjoyed wide popularity but minor engineering eccentricities have occurred and have been reported. We report another unusual feature seen in Activitrax models 8400, 8402, and 8403. This feature consists of continuing in a temporary mode while a different permanent mode was programmed. These eccentricities of the programming features are not very commonly seen, however, they can be somewhat perplexing to the physician following the patient. These unusual features are no longer present in the newer models being manufactured.


Mixed DNA/RNA polymers are cleaved by the hammerhead ribozyme.
A series of chemically synthesized oligodeoxyribonucleotides containing one or two ribonucleotides (DNA/RNA mixed polymers) at and/or adjacent to the cleavage site of the substrate can be cleaved by the "hammerhead" ribozyme. In comparison with the all-RNA substrate, the predominantly deoxyribonucleotide substrates have (1) lower optimal temperatures of cleavage, (2) approximately 6-fold higher Km's and 7-fold lower kcat's at 30 degrees C, and (3) 15-fold higher Km's and 8-fold lower kcat's at 37 degrees C. The extent to which the RNA substrate cleavage is inhibited in the presence of an all-DNA (KI = 13 microM) and an RNA substrate analogue with a dC at the cleavage site (KI = 0.96 microM) supports the contention that the formation of the ribozyme-substrate complex with the predominantly deoxyribonucleotide substrates (D substrates) is impaired. The weaker binding of D substrates was confirmed by thermal denaturation and determination of the Tm of the complex. Analysis of the kinetic data also suggests that the conformation of the catalytic core of the ribozyme-substrate complex differs from that of the all-RNA complex, a change that results from the presence of a DNA/RNA heteroduplex in the complex.


Association between environmental microbiota and indigenous bacteria found in hemolymph, extrapallial fluid and mucus of Anodonta cygnea (Linnaeus, 1758).
Bivalves filter and accumulate large numbers of microorganisms present in the harvesting water. A complete understanding of the balance between Anodonta cygnea and the microbiota present in their surrounding environment remains incomplete. Therefore, the aim of this study was to quantify and identify the indigenous bacteria in the biological fluids of A. cygnea collected from Mira Lagoon in northern Portugal. The results showed Vibrio metschnikovii and Aeromonas sobria as the dominant groups. The median for total bacteria from mucus was 3.1 × 10(3) CFU g(-1), whereas the range in means from fluids was 1.5 × 10(2) to 6.5 × 10(2) CFU ml(-1). During the experimental work, Escherichia coli and enterococci were not detected in healthy A. cygnea. However, the periodic detection of E. coli and enterococci in Mira lagoon revealed its presence in the water. Our observations suggest that A. cygnea has the ability to filter and eliminate E. coli, present in the surrounding environment, through an active phagocytic process conducted by hemolymph circulating cells, the hemocytes.


Clinical Recommendations for Epistaxis Management During the COVID-19 Pandemic.
Epistaxis is a common complaint in the general population, and its treatment is a common procedure in emergency departments. In the COVID-19 era, procedures involving airway management are a particular risk for health care workers due to the high virulence of the virus, the transmission through aerosol, and the risk of contagion from asymptomatic patients. In this article, we propose a simple memorandum of clinical recommendations to minimize the risk of operator infection deriving from epistaxis management. The correct use of personal protective equipment and strict compliance with the behavioral guidelines are essential to reduce the potential risk of infection. In particular, the use of filtering masks is strongly recommended since all patients, including those referring for epistaxis, should be treated as being COVID-19 positive in the emergency department. The safety of health care workers is essential not only to safeguard continuous patient care but also to limit virus transmission.


Probing hybridization parameters from microarray experiments: nearest-neighbor model and beyond.
In this article, it is shown how optimized and dedicated microarray experiments can be used to study the thermodynamics of DNA hybridization for a large number of different conformations in a highly parallel fashion. In particular, free energy penalties for mismatches are obtained in two independent ways and are shown to be correlated with values from melting experiments in solution reported in the literature. The additivity principle, which is at the basis of the nearest-neighbor model, and according to which the penalty for two isolated mismatches is equal to the sum of the independent penalties, is thoroughly tested. Additivity is shown to break down for a mismatch distance below 5 nt. The behavior of mismatches in the vicinity of the helix edges, and the behavior of tandem mismatches are also investigated. Finally, some thermodynamic outlying sequences are observed and highlighted. These sequences contain combinations of GA mismatches. The analysis of the microarray data reported in this article provides new insights on the DNA hybridization parameters and can help to increase the accuracy of hybridization-based technologies.


Dicopper(II) Metallacyclophanes with Electroswitchable Polymethyl-Substituted para-Phenylene Spacers.
Double-stranded anionic dinuclear copper(II) metallacyclic complexes of the paracyclophane type [Cu2L2](4-) have been prepared by the Cu(II)-mediated self-assembly of different para-phenylenebis(oxamato) bridging ligands with either zero-, one-, or four-electron-donating methyl substituents (L=N,N'-para-phenylenebis(oxamate) (ppba; 1), 2-methyl- N,N'-para-phenylenebis(oxamate) (Meppba; 2), and 2,3,5,6-tetramethyl- N,N'-para-phenylenebis(oxamate) (Me4ppba; 3)). These complexes have been isolated as their tetra-n-butylammonium (1 a-3 a), lithium(I) (1 b-3 b), and tetraphenylphosphonium salts (1 c-3 c). The X-ray crystal structures of 1 a and 3 c show a parallel-displaced π-stacked conformation with a smaller deviation from perpendicularity between the two benzene rings and the basal planes of the square planar Cu(II) ions when increasing the number of methyl substituents (average dihedral angles (ϕ) of 58.72(7) and 73.67(5)° for 1 a and 3 c, respectively). Variable-temperature (2.0-300 K) magnetic-susceptibility measurements show an overall increase of the intramolecular antiferromagnetic coupling with the number of methyl substituents onto the para-phenylene spacers (-J=75-95, 100-124, and 128-144 cm(-1) for 1 a-c, 2 a-c, and 3 a-c, respectively; H=-JS1×S2). Cyclic voltammetry (CV) measurements show a reversible one-electron oxidation of the double polymethyl-substituted para-phenylenediamidate bridging skeleton at a relatively low formal potential that decreases with the number of methyl substituents (E1=+0.33, +0.24, and +0.15 V vs. SCE for 1-3, respectively). The monooxidized dicopper(II) π-radical cation species 3' prepared by the chemical oxidation of 3 with bromine exhibits intense metal-to-ligand charge-transfer (MLCT) transitions in the visible and near-IR (λmax=595 and 875 nm, respectively) regions together with a rhombic EPR signal with a seven-line splitting pattern due to hyperfine coupling with the nuclear spin of the two Cu(II) ions. Density functional (DF) calculations for 3' evidence a characteristic iminoquinonoid-type short-long-short alternating sequence of C-N and C-C bonds for both tetramethyl-para-phenylenediamidate bridges and a large amount of spin density of negative sign mainly delocalized along each of the four benzene C atoms directly attached to the amidate N atoms, which is in agreement with a fully delocalized π-stacked monoradical ligand description. Hence, the spins of the two Cu(II) ions (SCu=1/2) that are antiparallel aligned in 3 (OFF state) become parallel in 3' (ON state). Further developments may be then envisaged for this new permethylated dicopper(II) paracyclophane with a redox noninnocent ligand as a prototype for molecular magnetic electroswitch.


Learning styles of preclinical students in a medical college in western Nepal.
Information on the learning styles of medical students are lacking in medical colleges in Nepal. Learning styles may be associated with student understanding and may predict success in examination. The present study was carried out to obtain information on learning styles and preferences for teaching of fourth semester medical students and note the association, if any, between respondents' personal characteristics and preferences for learning styles and types of teaching. The correlation between preferences for learning styles and types of teaching and performance in the second year university examination was also explored. The study was carried out during October 2003 at the Manipal College of Medical Sciences, Pokhara, Nepal using the Approaches and Study Skills Inventory (ASSIST) instrument. Information on the respondents' personal characteristics was collected. Respondents had to indicate their degree of agreement with a set of statements using a modified Likert-type scale. The statements were grouped into three main learning styles and two types of teaching. The median scores among different subgroups of respondents were compared using appropriate non-parametric tests (p<0.05). Ninety-two students (92%) participated; fifty-six were male. Thirty-one respondents were Nepalese, 48 were Indians. Majority were educated in English medium schools. The median scores for deep and surface learning styles were 64 and 49 respectively (maximum score=80). The scores for strategic learning was 75.5 (maximum score=100). There was no clear preference for any particular type of teaching. Indian students used more surface apathetic learning strategies compared to others. There was a negative correlation between surface learning and marks obtained in the final examination. The students mainly used deep and strategic learning styles. Differences in preference for learning styles and types of teaching were noted according the respondents' personal characteristics. This was a preliminary study and further studies are required.


Defects in ProTaper S1 instruments after clinical use: fractographic examination.
To investigate the mode of failure of a brand of nickel-titanium instruments separated during clinical use, by detailed examination of the fracture surface. A total of 122 ProTaper S1 instruments were discarded from an endodontic clinic at a stomatological school in China over a period of 17 months; 28 had fractured. These fractured instruments were ultrasonically cleaned, autoclaved and then examined under a scanning electron microscope. From the lateral view the fracture was classified into 'torsional' or 'flexural'. The specimens were then re-mounted and the presence of characteristics of shear failure and fatigue striations was recorded under high-power view of the fracture surface. The difference in the mean lengths of fractured segment between the shear and fatigue groups was compared using Student's t-test. Twenty-seven separated instruments were available for analysis. Under low-power magnification, only two fell into the category of 'torsional' failure when examined laterally; the others appeared to be 'flexural'. Close examination of the fracture surface revealed the presence of fatigue striations in 18 specimens. Nine instruments (including the two putative 'torsional' failures above) fell into the shear fracture group, in which fatigue striations were absent or characteristics of shear failure of the material were found. The mean length of fractured segments resulting from fatigue failure (4.3+/-1.9 mm) was significantly greater than that for shear failure (2.5+/-0.8 mm) (P<0.001, two-sample t-test). Examination of the fracture surface at high magnification is essential to reveal features that may indicate the possible origin of cracks and the mode of material failure. Macroscopic or lateral examination of separated instruments would fail to reveal the true mechanism of failure. Fatigue seems to be an important reason for the separation of rotary instruments during clinical use.


Are opioid antagonists effective in reducing self-injury in adults with intellectual disability? A systematic review.
Self-injury in people with intellectual disability (ID) may be due to variety of factors both environmental and biological. As the drive in UK is to manage people with ID and problem behaviours in the community, it is important to critically examine all treatment options available. As abnormalities in the endogenous opioid system may be a factor in some people with ID, we undertook a systematic review to evaluate the evidence for the effectiveness of opioid antagonists. Four electronic databases were searched for relevant journal articles. In addition, cross-referencing of pertinent reviews and a hand search for articles in major international ID journals between the years 2010 and 2012 was carried out to ensure that all relevant articles were identified. We also searched databases for unpublished clinical trials to overcome publication bias. Each database was searched up to present (February 2013) with no restrictions on the date of publication. The search terms consisted of broad expressions used to describe ID and autistic spectrum disorder as well as terms relating to opioid antagonists and specific drugs. All studies identified by the electronic database search and hand search were examined on the basis of title alone for relevance and duplication. The abstracts of the remaining papers were then scrutinised against the inclusion criteria. Where abstracts failed to provide adequate information, the full texts for these papers were obtained. All the full texts were then evaluated against the inclusion proforma. Two reviewers carried out all the stages of the process independently. The reviewers met to discuss their selections and where disagreements arose, these were settled by discussion with a member of the study group. Data from each study meeting the inclusion criteria was extracted on a pre-piloted data extraction form. The quality of each study was further assessed using the Jadad scale, a tool developed to assess the quality of randomised controlled trials. Out of 10 randomised control trials eight reported a reduction in the frequency of self-injurious behaviour. This meant that 62 participants out of 124 (50%) showed an improvement of which 61 were statistically significant. Forty-nine participants had autism. Eleven (9%) had minor side-effects. The improvement was more marked in people with severe and profound ID and was not affected by the coexistence of autism. This review suggests that some people respond to opioid antagonists with a reduction in self-injury but the trials do not predict who they may be. Future research may identify this sub-group when opioid antagonists may prove to be a useful addition in the pharmacotherapy of self-injury.


Competing risk analysis on outcome after hepatic resection of hepatocellular carcinoma in cirrhotic patients.
To investigate death for liver failure and for tumor recurrence as competing events after hepatectomy of hepatocellular carcinoma. Data from 864 cirrhotic Child-Pugh class A consecutive patients, submitted to curative hepatectomy (1997-2013) at two tertiary referral hospitals, were used for competing-risk analysis through the Fine and Gray method, aimed at assessing in which circumstances the oncological benefit from tumour removal is greater than the risk of dying from hepatic decompensation. To accomplish this task, the average risk of these two competing events, over 5 years of follow-up, was calculated through the integral of each cumulative incidence function, and represented the main comparison parameter. Within a median follow-up of 5.6 years, death was attributable to tumor recurrence in 63.5%, and to liver failure in 21.2% of cases. In the first 16 mo, the risk of dying due to liver failure exceeded that of dying due to tumor relapse. Tumor stage only affects death from recurrence; whereas hepatitis C infection, Model for End-stage Liver Disease score, extent of hepatectomy and portal hypertension influence death from liver failure (P < 0.05 in all cases). The combination of these clinical and tumoral features identifies those patients in whom the risk of dying from liver failure did not exceed the tumour-related mortality, representing optimal surgical candidates. It also identifies those clinical circumstances where the oncological benefit would be borderline or even where the surgery would be harmful. Having knowledge of these competing events can be used to weigh the risks and benefits of hepatic resection in each clinical circumstance, separating optimal from non-optimal surgical candidates.


Snail and slug play distinct roles during breast carcinoma progression.
Carcinoma progression is linked to a partially dedifferentiated epithelial cell phenotype. As previously suggested, this regulation could involve transcription factors, Snail and Slug, known to promote epithelial-mesenchymal transitions during development. Here, we investigate the role of Snail and Slug in human breast cancer progression. We analyzed Snail, Slug, and E-cadherin RNA expression levels and protein localization in large numbers of transformed cell lines and breast carcinomas, examined the correlation with tumor histologic features, and described, at the cellular level, Snail and Slug localization in carcinomas using combined in situ hybridization and immunolocalization. In contrast with transformed cell lines, Slug was found to colocalize with E-cadherin at the cellular level in normal mammary epithelial cells and all tested carcinomas. Snail also colocalized at the cellular level with E-cadherin in tumors expressing high levels of Snail RNA. In addition, Snail was significantly expressed in tumor stroma, varying with tumors. Slug and Snail genes were significantly overexpressed in tumors associated with lymph node metastasis. Finally, the presence of semidifferentiated tubules within ductal carcinomas was linked to Slug expression levels similar to or above normal breast samples. These results suggest that Snail or Slug expression in carcinoma cells does not generally preclude significant E-cadherin expression. They emphasize a link between Snail, Slug, and lymph node metastasis in a large sampling of mammary carcinomas, and suggest a role for Slug in the maintenance of semidifferentiated structures. Snail and Slug proteins seem to support distinct tumor invasion modes and could provide new therapeutic targets.


Chromophore pre-maturation for improved speed and sensitivity of split-GFP monitoring of protein secretion.
Complementation-dependent fluorescence is a powerful way to study co-localization or interactions between biomolecules. A split-GFP variant, involving the self-associating GFP 1-10 and GFP 11, has previously provided a convenient approach to measure recombinant protein titers in cell supernatants. A limitation of this approach is the slow chromophore formation after complementation. Here, we alleviate this lag in signal generation by allowing the GFP 1-10 chromophore to mature on a solid support containing GFP 11 before applying GFP 1-10 in analyses. The pre-maturated GFP 1-10 provided up to 150-fold faster signal generation compared to the non-maturated version. Moreover, pre-maturated GFP 1-10 significantly improved the ability of discriminating between Chinese hamster ovary (CHO) cell lines secreting GFP 11-tagged erythropoietin protein at varying rates. Its improved kinetics make the pre-maturated GFP 1-10 a suitable reporter molecule for cell biology research in general, especially for ranking individual cell lines based on secretion rates of recombinant proteins.


EVOLUTIONARY HISTORY OF NORTHERN HEMISPHERE NUCELLA (GASTROPODA, MURICIDAE): MOLECULAR, MORPHOLOGICAL, ECOLOGICAL, AND PALEONTOLOGICAL EVIDENCE.
By combining data from a variety of sources we explore patterns of evolution and speciation in Nucella, a widely studied genus of shallow-water marine neogastropods. We present a hypothesis of phylogenetic relationships for all of the currently recognized species of northern hemisphere Nucella, based on an analysis of 718 base pairs of nucleotide sequence from the mitochondrial cytochrome b gene. The order of appearance of species in the fossil record is congruent with this hypothesis. The topology of the inferred phylogeny of Nucella, coupled with ecological, morphological, and fossil evidence, was used to address three main questions: (1) At what time and by which route was the North Atlantic invaded from the North Pacific compared to prior studies of the trans-Arctic interchange? (2) Do patterns of molecular variation within species corroborate the importance of climatic cycles in driving speciation in north temperate marine animals? (3) Was radiation in the direction of increased or decreased ecological specialization, body size, or vulnerability to predation? Molecular evidence confirmed that the sole North Atlantic species, N. lapillus, arose from a North Pacific ancestor. Biogeographic and paleontological evidence supported the dispersal of Nucella, and perhaps other interchange species, via the Eurasian Arctic. Rather intriguingly, the linkage of N. lapillus to a western as opposed to eastern Pacific clade, and the biogeographic origins of the eastern Pacific species, parallel closely similar patterns observed in another genus of rocky-shore gastropods, Littorina. This congruence, in conjunction with information on the climatic and geographic histories of the region, as well as the geographic arrangement of mtDNA haplotypes within Nucella species, supports a model of speciation in Nucella driven by cycles of climatic amelioration and deterioration that began during the Miocene. Calibrations from the fossil record of Nucella suggest that third position transitions and transversions accrue at a rate of 3-4% and 0.5% respectively per million yr. This supports an early participation by Nucella in the trans-Arctic interchange, as suggested by paleobiogeographic studies. Consistent with the unstable taxonomic history of species of Nucella, we found few nonmolecular traits to be phylogenetically informative. Among North Pacific species, more recently derived species (N. canaliculata and the N. emarginata clade) were more ecologically specialized (narrower diet and habitat range). Consistent with extensive intraspecific variation, shell traits were quite labile evolutionarily: neither overall size nor development of antipredatory traits exhibited consistent evolutionary trends over the history of the genus. Nurse eggs (unfertilized eggs consumed by developing embryos) were an ancestral trait that was lost evolutionarily in the two clades that also exhibited increased body size, suggesting that these two life-history traits may be coupled. The reduced number of chromosomes in N. lapillus is clearly a derived state and is consistent with White's (1978) observations on chromosome evolution in other clades.


Mode conversion using stimulated Brillouin scattering in nanophotonic silicon waveguides.
We theoretically and numerically investigate Stimulated Brillouin Scattering generated mode conversion in high-contrast suspended silicon nanophotonic waveguides. We predict significantly enhanced mode conversion when the linked effects of radiation pressure and motion of the waveguide boundaries are taken into account. The mode conversion is more than 10 times larger than would be predicted if the effect of radiation pressure is not taken into account: we find a waveguide length of 740 μm is required for 20dB of mode conversion, assuming a total pump power of 1W. This is sufficient to bring the effect into the realm of chip-scale photonic waveguides. We explore the interaction between the different types of acoustic modes that can exist within these waveguides, and show how the presence of these modes leads to enhanced conversion between the different possible optical modes.


Anti-neurofascin antibody in patients with combined central and peripheral demyelination.
We aimed to identify the target antigens for combined central and peripheral demyelination (CCPD). We screened target antigens by immunohistochemistry and immunoblotting using peripheral nerve tissues to identify target antigens recognized by serum antibodies from selected CCPD and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) cases. We then measured the level of antibody to the relevant antigen in 7 patients with CCPD, 16 patients with CIDP, 20 patients with multiple sclerosis, 20 patients with Guillain-Barré syndrome, 21 patients with other neuropathies, and 23 healthy controls (HC) by ELISA and cell-based assays using HEK293 cells. At the initial screening, sera from 2 patients with CCPD showed cross-like binding to sciatic nerve sections at fixed intervals, with nearly perfect colocalization with neurofascin immunostaining at the node and paranode. ELISA with recombinant neurofascin revealed significantly higher mean optical density values in the CCPD group than in other disease groups and HC. Anti-neurofascin antibody positivity rates were 86% in patients with CCPD, 10% in patients with multiple sclerosis, 25% in patients with CIDP, 15% in patients with Guillain-Barré syndrome, and 0% in patients with other neuropathies and HC. The cell-based assay detected serum anti-neurofascin antibody in 5 of 7 patients with CCPD; all others were negative. CSF samples examined from 2 patients with CCPD were both positive. In anti-neurofascin antibody-positive CCPD patients, including those with a limited response to corticosteroids, IV immunoglobulin or plasma exchange alleviated the symptoms. Anti-neurofascin antibody is frequently present in patients with CCPD. Recognition of this antibody may be important, because patients with CCPD who are antibody positive respond well to IV immunoglobulin or plasma exchange.


A cost-utility analysis of the home parenteral nutrition program at Toronto General Hospital: 1970-1982.
We performed an economic evaluation of a home parenteral nutrition (HPN) program by measuring the incremental costs and health outcomes for a cohort of 73 patients treated at our institution from November 1970 to July 1982. Over a 12-year time frame, we estimate that HPN resulted in a net savings in health care cost of $19,232 per patient and an increase in survival, adjusted for quality of life, of 3.3 years, compared with the alternative of treating these patients in hospital with intermittent nutritional support when needed. This result was sensitive to assumptions made about the cost of the alternative treatment strategy. When these assumptions were most unfavorable to the HPN program, we estimated that HPN resulted in incremental costs of $48,180 over 12 years, $14,600 per quality-adjusted life-year gained. We conclude that the cost-utility of HPN compares favorably with other health care programs, when HPN is used to treat patients with gut failure secondary to conditions such as Crohn's disease or acute volvulus. Since only one patient with active malignancy was enrolled in our HPN program, these results should not be extrapolated to patients with active malignancy.


Transforming growth factor-beta 1 localization in normal and psoriatic epidermal keratinocytes in situ.
Transforming growth factor-beta 1 (TGF beta 1) is a potent inhibitor of epithelial cell proliferation and its effects on growth and differentiation have been extensively characterized in cultured keratinocytes. We used two TGF beta 1-specific polyclonal antibodies (anti-LC and anti-CC) to determine the presence of TGF beta 1 peptide in keratinocytes in sections of normal human skin in situ and in both plaque and nonplaque skin from individuals with psoriasis. In contrast to the differentiation phenotype expressed by keratinocytes in normal epidermis, keratinocytes in the psoriatic plaque exhibit a hyperproliferative/regenerative differentiation phenotype. Anti-TGF beta 1 staining was observed primarily in the epidermis. Anti-LC TGF beta 1 antibody stained nonproliferating, differentiated suprabasal keratinocytes intracellularly in normal skin but did not stain psoriatic plaques from five of seven patients. In contrast, anti-CC TGF beta 1 antibody stained suprabasal keratinocytes extracellularly in psoriatic plaques, but did not stain normal skin. Both anti-LC and anti-CC stained suprabasal keratinocytes intracellularly in nonplaque psoriatic skin. Thus, the conformation or structure of TGF beta 1 and its localization vary in keratinocytes with distinct differentiation phenotypes suggesting that TGF beta 1 is a potential modulator of keratinocyte differentiation in vivo. Selective association of TGF beta 1 with nonproliferating keratinocytes in the suprabasal layers of the epidermis and its exclusion from the proliferating keratinocytes in the basal layer suggest that it may be a physiological regulator of keratinocyte proliferation. In addition, the intracellular localization of TGF beta 1 peptide in both normal and psoriatic keratinocytes suggests that it is constitutively synthesized by epidermal keratinocytes in vivo.


Method for showing human spermatogenesis using Arachis hypogaea (AHA) lectin.
Using biotinylated Arachis hypogaea agglutinin (AHA) or peanut lectin (PNA) and an avidin-peroxidase procedure, the various stages of spermatid development were visualised with great clarity; a light haematoxylin counterstain permitted the easy recognition of spermatogenic cells in the same section. This method is particularly useful in the interpretation of poorly fixed material and may be helpful in studies of cyclical maturation of spermatozoa, irrespective of whether the material is obtained at biopsy or necropsy.


Epigenetics of autoantigens: new opportunities for therapy of autoimmune diseases.
The field of epigenetics requires that traditional divisions between scientific disciplines give way to cross-fertilization of concepts and ideas from different areas of investigation. Such is the case with research in autoimmunity. Recent discoveries of stimuli that induce autoimmunity reveal that epigenetic marks of autoantigens are recognized by autoreactive B and T cell receptors. Thus, insights into the initiation of autoimmunity, its prevention and therapy will arise from understanding the biochemistry, cell biology and microbiology of autoantigen epigenetics. Here, we highlight potential benefits from the inhibition of a histone modifying enzyme and the administration of a phosphorylated, spliceosome-derived peptide, in the treatment of autoimmunity.


Relational autonomy, care, and Jehovah's Witnesses in Germany.
Drawing from an ethics of care, relational approaches to autonomy have recently emerged in bioethics. Unlike individual autonomy with its emphasis on patients' rights, choice, and self-determination which has been the hallmark of bioethics consistent with the ideology of individualism in neoliberal democracies in Western countries, relational autonomy highlights the relatedness, interdependency, and social embeddedness of patients. By examining the mediating role that male Hospital Liaison Committee members in Germany play in facilitating care that supports Jehovah's Witnesses' refusal of blood transfusions, this article moves beyond 'dyadic relations' and contexts of caregiving. It also contributes to a deeper understanding of care and relational conceptualizations of Witness patients' autonomy globally.


Spatial Variation of Soil Organic Carbon and Total Nitrogen in the Coastal Area of Mid-Eastern China.
Soils play an important role in sequestrating atmospheric CO₂. Coastal tidal flats have been intensively reclaimed for food security and living spaces worldwide. We aimed to identify the changes of soil organic carbon (SOC) and total nitrogen (TN) following coastal reclamation and their spatial variation in the coastal area of mid-Eastern China to provide information for coastal cropland management. We measured SOC and TN of 463 soil samples in the coastal plain of mid-Eastern China. The results showed that SOC and TN increased highly from the uncultivated coastal tidal flat (2.49 g·kg-1 and 0.21 g·kg-1, respectively) to the cropland (10.73 g·kg-1 and 1.3 g·kg-1, respectively). After long-term cultivation, SOC and TN in the old farmland (12.98 g·kg-1 and 1.49 g·kg-1, respectively) were greater than those in the young farmland (5.76 g·kg-1 and 0.86 g·kg-1, respectively). The density of SOC in the uncultivated coastal tidal flat, young farmland, and old farmland were 0.68 kg·C·m-2, 1.52 kg·C·m-2, and 3.31 kg·C·m-2, respectively. The density of TN in the uncultivated coastal tidal flat, young farmland and old farmland were 0.05 kg·N·m-2, 0.23 kg·N·m-2, and 0.38 kg·N·m-2, respectively. The C/N (11.17) in the uncultivated coastal tidal flat was highest comparing to that in the young and old farmland due to lower nitrogen. The C/N increased from 6.78 to 8.71 following cultivation. Reclaimed coastal tidal flats had high carbon and nitrogen sequestration potential that not only mitigated the threat of global warming, but also improved soil fertility for crop production. Coastal management of cropland should consider the spatial distribution of SOC and TN to improve ecosystem services of coastal soils.


Efficient visible light-initiated hydrogenation of nitrobenzene for chemoselective production of aniline, azoxybenzene, azobenzene and hydrazobenzene over CQDs/CdS nanocomposites.
Carbon quantum dot (CQD)-decorated CdS nanocomposites were successfully fabricated via the self-assembly of CdS in the presence of preformed CQDs and were found to be efficient photocatalysts for the hydrogenation of nitrobenzene under visible light. Due to the presence of the frustrated Lewis acid-base pairs (FLPs) in their structure, CQDs act as an efficient catalyst to promote the proton-coupled hydrogenation of nitrobenzene over CQDs/CdS nanocomposites. Controllable and chemoselective hydrogenation of nitrobenzene to produce aniline, azoxybenzene, azobenzene and hydrazobenzene can be realized over CQDs/CdS via simply regulating the reaction medium including the hydrogen source, the solvent and the alkalinity. This study provides a highly efficient and economical photocatalytic system for the controllable and chemoselective hydrogenation of nitrobenzene under visible light. This work also highlights the great potential of semiconductor-based photocatalysis in light-initiated organic syntheses.


Association of dysfunctional breathing with health-related quality of life: A cross-sectional study in a young population.
Symptomatic hyperventilation (SH) is a pathological condition that manifests with breathlessness, dyspnea, light-headedness, anxiety, and paresthesia. However, little is known about the prevalence of SH and its association with health-related quality of life (HRQoL) in a young population. The Nijmegen questionnaire (NQ), which measures severity of SH, had not previously been cross-culturally translated into Korean. In this study, the NQ was cross-culturally translated into Korean (KNQ), using translation and back-translation methods. To examine the reliability and validity levels of the KNQ, as well as its association with HRQoL, 237 college students (21.38 ± 2.45 years) were asked to complete the KNQ, the Korean version of the general health questionnaire (K-GHQ-30) and the short form-36 (K-SF-36). The KNQ showed satisfactory reliability (Cronbach's α = 0.878). In the construct validity test, four factors (neuropsychological, respiratory, neurogastrointestinal, and neuromuscular) were extracted (% of total variance = 59.8). Using a KNQ cut-off score of 23 points, the prevalence of SH was 22.8%. Physical and mental HRQoL levels estimated by the K-GHQ-30 score and the 8 subscale scores of the K-SF-36 were lower in the SH group than in those of the non-SH group. It is concluded that the cross-culturally translated KNQ is reliable and valid, and management of SH may prevent a reduction in physical and mental HRQoL in a young population.


The children of the missed pill.
We assess the impact of exogenous variation in oral contraceptives prices-a year-long decline followed by a sharp increase due to a documented collusion case-on fertility decisions and newborns' outcomes. Our empirical strategy follows an interrupted time-series design, which is implemented using multiple sources of administrative information. As prices skyrocketed (45% within a few weeks), the Pill's consumption plunged, and weekly conceptions increased (3.2% after a few months). We show large effects on the number of children born to unmarried mothers, to mothers in their early twenties, and to primiparae women. The incidence of low birth weight and fetal/infant deaths increased (declined) as the cost of birth control pills rose (fell). In addition, we document a disproportional increase in the weekly miscarriage and stillbirth rates. As children reached school age, we find lower school enrollment rates and higher participation in special education programs. Our evidence suggests these "extra" conceptions were more likely to face adverse conditions during critical periods of development.


Genetic Characterization of Continually Evolving Highly Pathogenic H5N6 Influenza Viruses in China, 2012-2016.
H5N6 is a highly pathogenic avian influenza (HPAI) and a zoonotic disease that causes recurring endemics in East Asia. At least 155 H5N6 outbreaks, including 15 human infections, have been reported in China. These repeated outbreaks have increased concern that the H5N6 virus may cross over to humans and cause a pandemic. In February, 2016, peafowls in a breeding farm exhibited a highly contagious disease. Post-mortem examinations, including RT-PCR, and virus isolation, confirmed that the highly pathogenic H5N6 influenza virus was the causative agent, and the strain was named A/Pavo Cristatus/Jiangxi/JA1/2016. In animal experiments, it exhibited high pathogenicity in chickens and an estimated median lethal dose in mice of ~104.3 TCID50. A phylogenetic analysis showed that JA1/2016 was clustered in H5 clade 220.127.116.11. FG594-like H5N6 virus from Guangdong Province was the probable predecessor of JA1/2016, and the estimated divergence time was June 2014. Furthermore, we found that H5N6 influenza viruses can be classified into the two following groups: Group 1 and Group 2. Group 2 influenza viruses have not been detected since the end of 2014, whereas Group 1 influenza viruses have continually evolved and reassorted with the "gene pool" circulating in south China, resulting in the rise of novel subtypes of this influenza virus. An increase in the number of its identified hosts, the expanding range of its distribution, and the continual evolution of H5N6 AIVs enhance the risk that an H5N6 virus may spread to other continents and cause a pandemic.


Pathophysiology of peripheral muscle wasting in cardiac cachexia.
Many different mechanisms have been proposed to explain muscle wasting in patients with heart failure; however, the pathogenesis remains largely obscure. This manuscript looks at current developments concerning the pathophysiology of skeletal muscle wasting in cardiac cachexia. Many studies have shown that malnutrition, malabsorption, metabolic dysfunction, anabolic/catabolic imbalance, inflammatory and neurohormonal activation, and cell death play an important role in the pathogenesis of wasting in cardiac cachexia. However, the aetiology of the muscle changes is not entirely clear. In biopsies of skeletal muscles from animals with cardiac cachexia increased rates of protein degradation have been observed, with increased activity of the ubiquitin-proteasome proteolytic pathway. Skeletal muscle apoptosis may also play a role in muscle atrophy and wasting and can be partly prevented by neurohormonal inhibition, but it has recently been reported that in cachectic patients with chronic heart failure apoptosis is not the main pathway of cell death and muscle loss. Many hypotheses have been used to explain the pathogenesis of muscle wasting in cardiac cachexia. Cardiac cachexia is a multifactorial disorder, and the targeting of different pathways will be necessary for effective treatment. The immune and neurohormonal abnormalities present in chronic heart failure may play a significant role in the pathogenesis of the wasting process. It has been suggested that common pathogenetic mechanisms underlie the loss of muscle mass in different cachectic states. More studies are needed to show whether there is a common pathway in cardiac cachexia and the other cachectic states.


Ginkgo biloba and ovarian cancer prevention: epidemiological and biological evidence.
There is considerable interest in herbal therapies for cancer prevention but often with little scientific evidence to support their use. In this study, we examined epidemiological data regarding effects of commonly used herbal supplements on risk for ovarian cancer and sought supporting biological evidence. 4.2% of 721 controls compared to 1.6% of 668 cases regularly used Ginkgo biloba for an estimated relative risk (and 95% confidence interval) of 0.41 (0.20,0.84) (p=0.01); and the effect was most apparent in women with non-mucinous types of ovarian cancer, RR=0.33 (0.15,0.74) (p=0.007). In vitro experiments with normal and ovarian cancer cells showed that Ginkgo extract and its components, quercetin and ginkgolide A and B, have significant anti-proliferative effects ( approximately 40%) in serous ovarian cancer cells, but little effect in mucinous (RMUG-L) cells. For the ginkgolides, the inhibitory effect appeared to be cell cycle blockage at G0/G1 to S phase. This combined epidemiological and biological data provide supportive evidence for further studies of the chemopreventive or therapeutic effects of Ginkgo and ginkgolides on ovarian cancer.


Does topical hydrogen peroxide penetrate the cornea?
To determine under what conditions hydrogen peroxide (H2O2) can penetrate the cornea and cause increased concentrations of H2O2 in the aqueous humor. Rabbit corneas were exposed in vitro and in vivo to H2O2 concentrations up to 60 mmol/l either in a 600 microliter volume or as consecutive drops. H2O2 was measured over time either in the endothelial superfusate or in tapped samples of aqueous humor, and in the fluid applied to the ocular surface. The stability of exogenous H2O2 added directly to aqueous humor was also determined. Exogenous H2O2 in aqueous humor decays with a half-life of 20 minutes, chiefly as a result of catalase activity. When applied to the entire ocular surface, 600 microliters of 60 mmol/l H2O2 caused no change in the concentration in aqueous humor, but when applied to the corneal surface alone, penetration occurred at 18 mmol/l and above. When applied as eight 40-microliters drops to the ocular surface the threshold for H2O2 penetration was above 36 mmol/l. H2O2 is rapidly eliminated on the ocular surface, chiefly by enzyme activity of the conjunctiva and cornea. Threshold for penetration of H2O2 into the aqueous humor depends on volume, concentration, duration, and ocular surface exposed. In a healthy eye, exogenously derived H2O2 is eliminated by enzyme activity of the aqueous humor and tissues surrounding the anterior chamber.


Geographic and altitudinal allozyme variation in sorghum (Sorghum bicolor (L.) Moench) landraces from Ethiopia and Eritrea.
The amount and distribution of genetic variation was investigated in 48 sorghum landrace accessions, representing 13 regions of origin and three adaptation zones (lowland, intermediate and highland elevation) in Ethiopia and Eritrea. Assaying 11 enzymes systems, 23 putative loci were scored for a total of 27 alleles. Nineteen loci were monomorphic and fixed for the same allele, while the remaining 4 loci, each with 2 alleles, were polymorphic across the 48 accessions. The results show significant differences in allele frequencies among the accessions, regions of origin and the adaptation zones. However, all measures of genetic variation used show that the accessions maintained much lower levels of variation than the corresponding mean values for self-pollinating crop plants, confirming previous conclusions that sorghum is depauperated in allozymic variation. The total gene diversity was 0.25, which partitioned 59% within and 41% among accessions. The latter was largely due to variation among accessions within the adaptation zones (38%), while only 3% was due to variation among accessions between the adaptation zones. Similarly, most of the total gene diversity was found within the regions of origin (80%) and within the adaptation zones (97%). Both the dendrogram constructed from NEI's unbiased genetic distance and the plot of the first two principal components distinguished three groups of regions. The level of gene flow was low among accessions, regions of origin and among accessions within adaptation zones, but high among adaptation zones. The results are discussed with emphasis on genetic resources conservation and utilization.


Alpha-adrenoceptor blocking properties of vesamicol.
The side-effects of vesamicol, an inhibitor of acetylcholine storage, on alpha 1- and alpha 2-adrenoceptors have been studied in the isolated rat vas deferens. Antagonism of alpha 1-adrenoceptors was determined from the ability of vesamicol to reduce contractions elicited by exogenous noradrenaline. Antagonism of alpha 2-adrenoceptors was determined from the ability of vesamicol to block the inhibitory effects of the alpha 2-adrenoceptor agonist clonidine on electrically evoked twitches. In the absence of noradrenaline uptake block, (-)-vesamicol, the isomer active at cholinergic synapses, produced a leftward shift of the noradrenaline concentration-effect curve. This effect was abolished by desipramine suggesting that it is due to an ability of (-)-vesamicol to block uptake1. In the presence of noradrenaline uptake blockers, (-)-vesamicol produced a competitive, non-selective block of both alpha 1- and alpha 2-adrenoceptors with a Kd of around 40 microM (pA2 4.4). (+)-Vesamicol, the isomer that has no activity at cholinergic synapses, was equipotent with the (-)-isomer for blocking alpha 2-adrenoceptors. In addition to its alpha-adrenoceptor antagonist activity, (-)-vesamicol augmented the maximum response of the tissue to exogenous and endogenous noradrenaline. This study was unable to determine the exact nature of this effect. We suggest that the alpha-adrenoceptor blocking activity of vesamicol is a function of the phenylpiperidino moiety of the molecule.


Gamma interferon (IFN gamma) and IFN alpha/beta suppress murine myeloid colony formation (CFU-C)N: magnitude of suppression is dependent upon level of colony-stimulating factor (CSF).
The effect of different types of interferon (IFN) on macrophage and granulocyte colony formation (CFU-C) in vitro was studied using bone marrow cells from C57BL/6 mice. CFU-C formation was measured at 7 days using a standard methylcellulose culture system with L-cell conditioned medium (LCCM) as a source of colony-stimulating factor activity (CSF), IFN gamma was obtained from staphylococcal enterotoxin A- (SEA) stimulated mouse spleen cells and was partially purified (50-fold) using affinity chromatography. IFN alpha/beta was obtained from Newcastle disease virus-infected mouse L-cells and was partially purified (286-fold) using an AcA 202 column. IFN gamma inhibited CFU-C formation in a dose-dependent manner and was 100 times more inhibitory than IFN alpha/beta. IFN gamma completely suppressed CFU-C formation with as little as 15 units of antiviral activity. In contrast, 1000 to 2000 units of antiviral activity of IFN alpha/beta was required for complete suppression of CFU-C formation. The ability of IFN gamma to inhibit CFU-C formation was completely abolished after pH 2 treatment (24 hr), heat treatment (60 degrees C, 2 hr), or treatment with a specific antiserum against IFN gamma, which indicated that IFN gamma was the mediator of CFU-C inhibition. When IFN gamma and IFN alpha/beta were mixed together and added to bone marrow cells, they had a synergistic effect on the suppression of CFU-C formation. The level of inhibition mediated by both IFN gamma and IFN alpha/beta was totally dependent upon the amount of CSF present in the culture system; increasing the level of CSF could completely overcome the IFN suppressive effect. These results suggest that IFN gamma and IFN alpha/beta may have regulatory roles in hematopoiesis.


Medical resources after nuclear war. Availability v need.
In defining capacity to "survive" a massive nuclear exchange, it is important to assess the medical resources that will be available in the post-nuclear war world. Approximately 80% of these resources--hospital beds and personnel, blood, drugs, and medical supplies--will have been destroyed, since they are located in or near the densely populated areas that constitute primary targets of attack. Casualty estimates published by federal agencies, together with data from the Hiroshima-Nagasaki experience, suggest the numbers and types of injuries that will afflict the US population. With a probable 48,000 surviving physicians to treat 32 million casualties, there will be one physician for every 663 patients. Of the trauma and burn victims, approximately 55% will require hospitalization; this will mean 64 patients for each available hospital bed. Data from recent wars have been utilized to determine the trauma-related blood requirements in the post-nuclear war world. Of the 64 million units of whole blood needed, only 14,000 will be available. Other medical resources will be in equally short supply. This disparity between need and availability indicates the difficulty of developing a meaningful medical response for the surviving injured.


Prioritization in Somali health system strengthening: a qualitative study.
After years of decline and disintegration, the Somalia Federal Government alongside international and domestic partners is beginning the process of rebuilding its national health system. In this study, we aim to shed light on the current approaches to health system strengthening, as viewed by stakeholders closely involved in its development. Key informant interviews were undertaken with health and development professionals working within all three administrative regions of Somalia, as well as with Somali ministry of health officials, global health and policy specialists with interests in health system reconstruction in fragile states. A review of published and grey literature on Somalia, health systems, fragile and conflict-affected countries using PubMed and Reliefweb was also conducted. Technical documents designed for Somali health system building by external development partners were also reviewed. Key priorities identified by participants were, strengthening of local governance and management capacity, scaling-up efforts to structure a robust health financing mechanism, engagement with the burgeoning and dynamic private sector, as well as investing in the appropriate human resources for health. The study found that there was widespread agreement among participants that health system strengthening through a coordinated system would improve long-term capacity in Somalia's health sector. Future research should focus on the evaluation of the modalities by which health system strengthening interventions are implemented, on neglected topics such as mental health within the Somali health system, as well as on population-level barriers to accessing health systems.


[Contribution to the study of labeled neurohypophysial hormones. Preliminary data on the properties of the macromolecular compound: vasopressin-dextran (author's transl)].
The neuropeptide binding sites at the level of their target cells can be localized by several morphological methods. For one of the neurohypophysial hormones, vasopressin, not all labelling techniques can be applied: radioiodinated vasopressin has no biological activity; only 3Hvasopressin can be used. Immunocytochemical evidence for vasopressin receptors must be supported by complementary data in order to demonstrate the specificity of the binding. A new labelled ligand is prepared: vasopressin-dextran. In vivo, this macromolecular compound has antidiuretic properties equivalent to those of free vasopressin. In vitro, it gives a cross reaction with specific anti-vasopressin antibodies. For the same macromolecular compound, the ratio between the conjugated vasopressin estimated through R.I.A. and that assayed by biological method was 30.


Fabrication of lab-on chip platforms by hot embossing and photo patterning.
In this paper, we review the approaches developed in our laboratory to fabricate polymer-based microfluidic devices to suit a range of applications in bio- or chemical analysis. Thermoplastic materials such as polycarbonate (PC) and poly(methyl methacrylate) (PMMA) are used to fabricate microfluidic devices via hot embossing. To emboss microchannels, we use hard stamps fabricated in silicon or soft stamps molded on poly(dimethylsiloxane) (PDMS). Hard stamps are fabricated on silicon wafers through photolithography and deep reactive ion etching (DRIE). Soft stamps are fabricated by casting PDMS prepolymer on silicon molds. To enclose the fluidic channels, direct fusion bonding was found to produce the highest bond strength with minimal structural deformation. One-step photolithographic methods have also been explored to produce via photochemical patterning microfluidic structures in photocurable materials. We use the photocurable capabilities of a PDMS copolymer, which incorporates a methacrylate crosslinker. Microfluidic channels are produced via one step-photopatterning processes by crosslinking the prepolymer mixture through a photomask. The smaller feature size attainable was 100 microm. Structures with higher spatial resolution are fabricated through a photoimprinting process whereby a mold is pressed against the precured mixture during UV crosslinking exposure. The application of the fabricated fluidic devices in electrophoretic ion analysis is also presented.


Carcinoma of unknown primary site treated with Carboplatin + Paclitaxel + bevacizumab + erlotinib and its maintenance chemotherapy.
About 3% of all cancer patients suffer from carcinoma of unknown primary site (CUP). In spite of its rarity, we will encounter them. While CUPs manifest a wide variety of clinical presentations, they have often resulted in poor prognosis. Although platinum/taxane combination chemotherapy, e.g. carboplatin (CBDCA) + paclitaxel (PTX) is widely used for patients suffering from CUP, the response rate is only about 30-40% and the median overall survival (OS) is only 9 months, which means that improvement is needed. Among the new regimens, the combination of CBDCA, PTX, bevacizumab (BEV) and erlotinib is thought to be highly promising. Herein, we report a case with CUP treated with this regimen and his maintenance therapy. Our patient was a 75-year-old man who was admitted with a left neck lump. CT revealed systemic massive lymphadenopathy. In spite of various investigations for primary origin, he was diagnosed with CUP and treated with CBDCA + PTX + BEV + erlotinib (AUC 6 + 175 mg/m(2) + 15 mg/kg + 150 mg). Since the evaluation of the efficacy indicated partial response, maintenance chemotherapy (BEV and erlotinib) was performed. Chemotherapy was continued for 9 months until the patient was in a progressive disease state with meningeal dissemination. He died 12 months after the initiation of chemotherapy, which is a longer period than the previously reported OS. Of note, according to our case, CBDCA + PTX + BEV + erlotinib and its maintenance chemotherapy are feasible and well tolerated for CUP.


Intra-epithelial subpopulations of T lymphocytes and Langerhans cells in oral lichen planus.
This study has addressed the question of whether there is selective recruitment and distribution of intra-epithelial leucocytes in lesions of oral lichen planus (OLP). T-lymphocyte subsets were examined in the epithelium and peripheral blood of patients and controls using flow cytometry and double immunofluorescence, and the relationship between keratinocyte intercellular adhesion molecule-1 (ICAM-1) expression with T-lymphocyte and Langerhans cell (LC) distribution was examined. The circulating 'memory' subset (CD45RO+) of T-helper cells (CD4+) was increased from 49.1% in controls to 65.7% in patients (P=0.005), while the 'naive' subset (CD45RA+), which was absent from control epithelium, comprised 24% of helper cells in OLP (P=0.016). Fewer LC expressed CD45RO in OLP than in controls (P=0.037) and all T-cell and LC counts were significantly raised in ICAM-1-expressing areas of epithelium. These data demonstrate changes in intra-epithelial T-lymphocyte and LC populations compared with normal oral mucosa and suggest there is selective recruitment in OLP. In addition, keratinocyte ICAM-1 expression does appear to be associated with accumulation of infiltrating T lymphocytes and LC.


Direct atomic force microscopy observation of DNA tile crystal growth at the single-molecule level.
While the theoretical implications of models of DNA tile self-assembly have been extensively researched and such models have been used to design DNA tile systems for use in experiments, there has been little research testing the fundamental assumptions of those models. In this paper, we use direct observation of individual tile attachments and detachments of two DNA tile systems on a mica surface imaged with an atomic force microscope (AFM) to compile statistics of tile attachments and detachments. We show that these statistics fit the widely used kinetic Tile Assembly Model and demonstrate AFM movies as a viable technique for directly investigating DNA tile systems during growth rather than after assembly.


Antibiotic therapy of hospitalized patients with community-acquired pneumonia: an international perspective from the CAPO Cohort Study.
The American Thoracic Society and the Infectious Diseases Society of America have developed evidence-based guidelines for the therapy of hospitalized patients with community-acquired pneumonia (CAP). In an attempt to evaluate if the care provided to hospitalized patients with CAP is in compliance with the care recommended by national guidelines, an international network of investigators has been collecting data from 40 hospitals in 13 countries. The care provided in the following areas of antibiotic therapy was analyzed: empiric antibiotic therapy, timing of initial antibiotic therapy, and switch from intravenous to oral antibiotic therapy. Lack of compliance with national guidelines was identified in all areas of antibiotic therapy. Compliance at the local level can be improved with the implementation of a hospital-based pneumonia quality improvement team. Improving compliance with national guidelines recommendations will produce a beneficial effect in CAP clinical and economic outcomes.


A sex- and age-limited ossification pattern in human costal cartilages.
In our continuing development of a roentgenographic method of determining age, race, and sex of cadaveric material, an absolutely distinctive pattern of ossification of the costal cartilages in older women has been identified. This ossification pattern has been found only in women over the age of 50 years and largely is restricted to those over 60 (i.e., remotely postmenopausal). Not encountered in men, this age/sex distinctive pattern is found in about one-third of the adult female autopsy population. It consists of rounded, solitary, or coalescent ossified foci confined to the central portions of the costal cartilages. These foci do not extend to the perichondrium and only very rarely involve the peristernal junctions. When this x-ray pattern is present, the decedent can be identified as an elderly female with great certainty.


Isolation, motivation and balance: living with type 1 or cystic fibrosis-related diabetes.
To explore patients' responses to developing and managing cystic fibrosis-related diabetes and to contrast their views with those of individuals with type 1 diabetes mellitus. The incidence of diabetes among people with cystic fibrosis has increased with improvement in life expectancy. However, little is known about how patients respond to and manage cystic fibrosis-related diabetes, and how this compares with people living with type 1 diabetes mellitus. Qualitative research was undertaken in order to fully explore meanings and views. Semi-structured telephone or face-to-face interviews were conducted with patients who had cystic fibrosis-related diabetes or type 1 diabetes mellitus, during which, they discussed diagnosis and management of diabetes. Framework analysis was employed to identify themes and to consider similarities and differences between the two groups. Eleven cystic fibrosis-related diabetes and 12 type 1 diabetes mellitus patients were interviewed in 2006. Patients with cystic fibrosis-related diabetes described their diabetes diagnosis as a progression of their primary illness, management of which was important owing to the benefits it brought to their cystic fibrosis. Those with type 1 diabetes mellitus were more likely to report feeling psychologically low because of diabetes and to list long-term complications as a key factor motivating self-management. Both groups struggled to balance the demands of diabetes with other life and health obligations, and experienced isolation because of diabetes. Conclusions. Variation in perceptions recalled during interviews stemmed from diabetes being part of an existing life-threatening chronic illness in people with cystic fibrosis-related diabetes. Similarities and differences in attitudes and management practices were found, with less urgency regarding glucose monitoring and fewer information resources available for those with cystic fibrosis-related diabetes. Both groups need support for optimal diabetes management and access to appropriate resources outside specialist clinics. Web-based technologies could prove useful for those with cystic fibrosis-related diabetes as face-to-face interaction may be prevented owing to the risk of cross-infection.


Recent progress in quantum photonic chips for quantum communication and internet.
Recent years have witnessed significant progress in quantum communication and quantum internet with the emerging quantum photonic chips, whose characteristics of scalability, stability, and low cost, flourish and open up new possibilities in miniaturized footprints. Here, we provide an overview of the advances in quantum photonic chips for quantum communication, beginning with a summary of the prevalent photonic integrated fabrication platforms and key components for integrated quantum communication systems. We then discuss a range of quantum communication applications, such as quantum key distribution and quantum teleportation. Finally, the review culminates with a perspective on challenges towards high-performance chip-based quantum communication, as well as a glimpse into future opportunities for integrated quantum networks.


Relationship between endocrine resistance and the periods of adjuvant endocrine treatment for hormone receptor-positive, HER2-negative breast cancer.
Current guidelines define primary and secondary endocrine resistance according to the periods of adjuvant endocrine therapy (adj-ET); however, the relationship between adj-ET period and endocrine resistance remains unclear. We examined progression-free survival (PFS) after primary ET for recurrent hormone receptor-positive/HER2-negative breast cancer, and evaluated the relationship between endocrine resistance and the periods of adj-ET. We assessed PFS among 183 patients who received ET as primary treatment for the first recurrence, according to the period of adj-ET (adj-ET < 1 year, 1-2 years, ≥2 years, and completion). Patients who relapsed during the first year of adj-ET had the significantly shortest PFS. PFS did not significantly differ between patients who relapsed at 1-2 years of adj-ET and patients who relapsed while on adj-ET but after the first 2 years. Relapse at 1-2 years after adj-ET initiation might be better classified as secondary endocrine resistance rather than primary endocrine resistance.


A Retrospective Study of Coronary Artery Bypass Grafting with Low-Thermal Plasma Dissection Device Compared to Conventional Monopolar Electrosurgery.
The objective of this study is to compare the effects of conventional monopolar electrosurgery (CMES) and low-thermal plasma kinetic cautery (PKC) on complications such as bleeding, abnormal wound healing, pain, and drainage in patients who underwent on-pump coronary artery bypass grafting (CABG). This retrospective clinical study included 258 patients undergoing CABG; the patients were randomized to PKC (PEAK PlasmaBlade, n=153) and CMES (n=105) groups. The patients' clinical data were examined retrospectively for biochemical variables, postoperative drainage, post-surgery erythrocyte suspension transfusion count, surgical site pain examined with visual analogue scale (VAS), and wound healing. Two-sided P-value > 0.05 was considered as statistically significant. The median post-surgery erythrocyte suspension transfusion number was significantly lower with PKC compared to CMES (0 [0-1] vs. 1 [1-4], respectively, P<0.001). Mean postoperative drain output and time until removal of drain tubes were significantly lower with PKC compared to CMES (300±113 vs. 547±192 and 1.95±1.5 vs. 2.44±1.8; P<0.001 and P=0.025, respectively). Mean VAS score for spontaneous and cough-induced pain were significantly lower with PKC compared to CMES (1.98±1.51 vs. 3.94± 2.09 and 3.76±1.46 vs. 5.6±1.92; P<0.001 for both comparisons). Reoperation due to bleeding was significantly higher with CMES compared to PKC (0 vs. 11 [7.2%], P=0.001). Use of PKC during CABG considerably reduces postoperative drainage, need for blood transfusion, reoperation due to bleeding, and postoperative pain. PCK appears to be a good alternative to CMES for CABG.


Fabrication of a gel particle array in a microfluidic device for bioassays of protein and glucose in human urine samples.
This paper describes a simple method for fabricating a series of poly(ethylene glycol) diacrylate (PEG-DA) hydrogel microstructures inside microfluidic channels as probe for proteins and glucose. In order to demonstrate the feasibility of this newly developed system, bovine serum albumin (BSA) was chosen as a model protein. PEG microcolumns were used for the parallel detection of multiple components. Using tetrabromophenol blue (TBPB) and the horseradish peroxidase/glucose oxidase reaction system, bovine serum albumin (BSA) and glucose in human urine were detected by color changes. The color changes for BSA within a concentration range of 1-150 μM, and glucose within a range of 50 mM-2 M could be directly distinguished by eyes or precisely identified by optical microscope. To show the practicability of the gel particle array, protein and glucose concentrations of real human urine samples were determined, resulting in a good correlation with hospital analysis. Notably, only a 5 µL sample was needed for a parallel measurement of both analytes. Conveniently, no special readout equipment or power source was required during the diagnosis process, which is promising for an application in rapid point-of-care diagnosis.


Impact of Dental Implant Surface Modifications on Osseointegration.
Objective. The aim of this paper is to review different surface modifications of dental implants and their effect on osseointegration. Common marketed as well as experimental surface modifications are discussed. Discussion. The major challenge for contemporary dental implantologists is to provide oral rehabilitation to patients with healthy bone conditions asking for rapid loading protocols or to patients with quantitatively or qualitatively compromised bone. These charging conditions require advances in implant surface design. The elucidation of bone healing physiology has driven investigators to engineer implant surfaces that closely mimic natural bone characteristics. This paper provides a comprehensive overview of surface modifications that beneficially alter the topography, hydrophilicity, and outer coating of dental implants in order to enhance osseointegration in healthy as well as in compromised bone. In the first part, this paper discusses dental implants that have been successfully used for a number of years focusing on sandblasting, acid-etching, and hydrophilic surface textures. Hereafter, new techniques like Discrete Crystalline Deposition, laser ablation, and surface coatings with proteins, drugs, or growth factors are presented. Conclusion. Major advancements have been made in developing novel surfaces of dental implants. These innovations set the stage for rehabilitating patients with high success and predictable survival rates even in challenging conditions.


[Echocardiography diagnosis of diastolic heart failure].
Left ventricular diastolic dysfunction can be diagnosed if clinical signs of heart failure and normal ejection fraction are found. Beside clinical signs of heart failure and criteria from catheterization studies like abnormal left ventricular relaxation, filling and/or compliance echocardiography provides valuable parameters for the assessment of diastolic dysfunction. By the use of various parameters diastolic dysfunction can be differentiated into four degrees of severity, which are of great prognostic importance. If more than one echocardiographic parameter is used, sensitivity for the assessment of diastolic dysfunction becomes nearly 100%. Conventional parameters include isovolumetric relaxation time (IVRT) measured by pulsed Doppler, the ratio of rapid filling and atrial filling velocity (E/A), deceleration time of rapid mitral inflow as well as the ratio of systolic and diastolic pulmonary venous flow velocities. In patients with signs of diastolic heart failure and a normal E/A ratio pulmonary venous flow pattern can help to unmask "pseudonormalization" as the transition from abnormal relaxation to restriction. These parameters, however, are preload-dependent and do not provide intrinsic left ventricular properties. Even in atrial fibrillation, left ventricular filling pressure can be assessed. Two novel approaches, color Doppler M-mode of left ventricular inflow and tissue Doppler of the mitral annulus, are relatively preload-independent and allow direct estimation of relaxation and filling pressure. By the means of real-time 3-D echocardiography we developed a new method for the non-invasive assessment of rapid filling rate (PFR), thereby completing the echocardiographic approaches to determine diastolic dysfunction. The broad spectrum of approaches available today makes echocardiography the first choice for the assessment of diastolic dysfunction.


[Characteristics of secondary immunologic deficiency in children with chronic hepatitis B and the methods of its correction].
A study was made of the immune system of patients with chronic HB-viral infection who showed the signs of secondary immundeficiency. The high frequency of the impairment of immunocompetent cells seen in chronic hepatitis B was established as was the appearance of different-temperature autolymphocytotoxins in response to the infection of mono-nuclears in all the disease stages. The treatment with thymalin proved effective in patients with the lack of cold autolymphocytotoxins or in those with low activity of the latter ones. The combined treatment (decaris plus prednisolone) turned out effective in children with a pronounced autoimmune component of the process (the presence of cold autolymphocytotoxins). It has been shown that the discovered interrelations between the different components of the immune system are conductive to the determination of the pathological process type and the choice of adequate therapy.


Suprasellar germinomas (ectopic pinealomas): aspects of immunological characterization and successful chemotherapeutic responses in recurrent disease.
Two patients with suprasellar germinomas were initially treated successfully with radiotherapy, but subsequently they developed recurrent tumor 2 1/2 and 12 years later. The recurrent tumor was solely extraneural in the first patient because of seeding from a ventriculoperitoneal shunt, and in the second patient the tumor recurred as its initial site as well as in the 4th ventricle. Both tumors secreted the beta-subunit of human chorionic gondadotropin. A dramatic tumor response was seen in both patients with systemic chemotherapy consisting of a combination of cis-platinum, bleomycin, and vinblastine. The "small cells" in one of the suprasellar germinomas were shown to be predominately T lymphocytes on the basis of an examination of the cell surface markers on these cells. (Neurosurgery, 7: 352-358, 1980).


Efficacy of combined hormonal vaginal ring in comparison to combined hormonal pills in heavy menstrual bleeding.
To compare the efficacy, acceptability and compliance of combined hormonal vaginal ring (CVR), with combined hormonal pills (CHP) in patients with heavy menstrual bleeding (HMB). This prospective study was conducted in 50 women with HMB in age group of 25-40 years. Patients were divided in two groups of 25 each and followed for six treatment cycles. In each group, cycle comprised of three weeks of CVR (releases 15μg of EE and 120μg of the etonogestrel per day) or CHP (containing 30μgm of EE and 150μgm of LNG) use, followed by one ring or pill free week. After each cycle, patients were evaluated about the amount of blood loss and duration of bleeding by the pictoral blood assessment chart (PBAC), early bleeding (EWB), continued bleeding (CWB), intermenstrual bleeding, intended bleeding, compliance, and user acceptability. The collected data were analyzed using the Chi square test, t-test and ANOVA test. Reduction in PBAC score for CVR (70.73%) and CHP group (70.02%), duration of bleeding and incidence of EWB was comparable among the two groups. The incidence of intermenstrual bleeding was lower in CVR than in CHP group in cycle 3 and 4 with significant p value. The incidence of CWB was significantly lower and the incidence of intended bleeding pattern in CVR group was significantly higher in cycle 3, 4, 5 and 6, signifying better cycle control. Compliance was also higher in CVR (88%) than CHC (75.33% of all cycles). This trial suggests that both the CVR and CHP are very effective short-term treatments for HMB in reproductive age group. However, women had better cycle control and compliance with CVR. This may be an attractive option among the wide variety of medications used to treat HMB.


Novel decomposition of polycarbonate and effect for marine ecosystem.
Analysis of pollution of the ocean plastics is presently being extensively carried out but special attention should be direct to matters. It is widely believed that plastic dose not decompose in the ocean. Certain contaminants, bisphenol-A (BPA) that serves the material for polycarbonate (PC) and epoxy resin (EPX) both of which may possibly be elute or degrade from commercial products, have often been detected in rivers, lakes and oceans. To clarify in detail the extend of this impact of this situation, purified PC (BPA free) was decomposed at temperatures range 50-230 °C. PC was seen to start decomposing at 50 °C over a 3 day period to generated 11 μg kg-1 BPA. Based on the rate constants of BPA, the activation energy was calculated 42.0 kJ mol-1. Since this value is almost same as the EPX and polystyrene (PS) of each decomposition. Based on the PC decomposition rate and the actual BPA value in the deep sea, the 280 million metric tons (MT) BPA in the world ocean was estimated. Unlike plastics, BPA shows endocrine disrupting in fish. It should thus be considered that degraded PC and EPX pose a serious threat to the marine ecosystem, directly.


Multiple primary cancers in families with Li-Fraumeni syndrome.
Li-Fraumeni syndrome is a dominantly inherited disorder characterized by early-onset breast cancer, sarcomas, and other cancers in children and young adults. Members of families with this syndrome also develop multiple primary cancers, but the frequency is unknown. To approach this issue, we quantified the incidence of second and third primary cancers in individuals from 24 Li-Fraumeni kindreds originally diagnosed with cancer during the period from 1968 through 1986. The relative risk (RR) of subsequent cancers and 95% confidence intervals (CIs) were calculated by use of population-based incidence data from the Connecticut Cancer Registry. Kaplan-Meier analysis was used to determine the cumulative probability (+/- standard error) of subsequent cancers. Among 200 Li-Fraumeni syndrome family members diagnosed with cancer, 30 (15%) developed a second cancer. Eight individuals (4%) had a third cancer, while four (2%) eventually developed a fourth cancer. Overall, the RR of occurrence of a second cancer was 5.3 (95% CI = 2.8-7.8), with a cumulative probability of second cancer occurrence of 57% (+/- 10%) at 30 years after diagnosis of a first cancer. RRs of second cancers occurring in families with this syndrome were 83.0 (95% CI = 36.9-187.6), 9.7 (95% CI = 4.9-19.2), and 1.5 (95% CI = 0.5-4.2) for individuals with a first cancer at ages 0-19 years, 20-44 years, and 45 years or more, respectively. Thirty (71%) of 42 subsequent cancers in this group were component cancers of Li-Fraumeni syndrome. Compared with the general population, members of Li-Fraumeni syndrome families have an exceptionally high risk of developing multiple primary cancers. The excess risk of additional primary cancers is mainly for cancers that are characteristic of Li-Fraumeni syndrome, with the highest risk observed for survivors of childhood cancers. Cancer survivors in these families should be closely monitored for early manifestations of new cancers.


Direct observation of the transmembrane recruitment of band 3 transport sites by competitive inhibitors. A 35Cl NMR study.
Numerous models describing anion exchange across the red cell membrane by band 3 have been discussed in literature. These models are readily distinguished from one another by an experiment which tests the ability of band 3 transport sites to be recruited to one side of the membrane. In order to observe directly the transmembrane recruitment of transport sites, we have developed 35Cl NMR techniques that resolve the two transport site populations on opposite sides of the membrane. Using these techniques, we show that the inhibitors 4,4'- dinitrostilbene -2,2'-disulfonate and p- nitrobenzensulfonate each recruit all of the transport sites on both sides of the membrane to the extracellular facing conformation. This result indicates that band 3 has an alternating site transport mechanism: each band 3 transport unit possesses a single functional transport site which is alternately exposed first to one side of the membrane then to the other.


The PSIPRED Protein Analysis Workbench: 20 years on.
The PSIPRED Workbench is a web server offering a range of predictive methods to the bioscience community for 20 years. Here, we present the work we have completed to update the PSIPRED Protein Analysis Workbench and make it ready for the next 20 years. The main focus of our recent website upgrade work has been the acceleration of analyses in the face of increasing protein sequence database size. We additionally discuss any new software, the new hardware infrastructure, our webservices and web site. Lastly we survey updates to some of the key predictive algorithms available through our website.


Multisystem Inflammatory Syndrome in Adults (MIS-A) Associated with SARS-CoV-2 Infection in a Young Adult Case from Turkey.
Weeks and even months after recovering from the SARS-CoV-2 infection, clinically more severe cases are being reported, which are suggestive of COVID-19- related multisystemic inflammatory syndromes (MIS). Firstly on March 2020, this condition was reported to be COVID-19 related to children (MIS-C). Since June 2020, a syndrome similar to multisystem inflammatory syndrome in adults (MIS-A) came to be noticed in adults as well. We reported here a case of 24-year-old young woman who had gone to a hospital with abdominal pain and later developed a severe cough, followed by development of subconjunctival bleeding, pericardial effusion, pleural effusion, and intra-abdominal fluid that we deemed them to be acute multisystemic clinical symptoms, 47 days after she had undergone a COVID-19 infection of mild clinical severity. It should be kept in mind that a multisystemic inflammatory syndrome along with a delayed immune response during COVID-19 disease can be seen not only in children but also in young adults, and seemingly severe clinical and laboratory findings can improve by controlling the inflammatory process.


Suppressive therapy after surgical treatment of thyroid gland cancer in patients with mastopathy.
State of lactation system during oncological disorders of thyroid gland is one of the poorly studied topics of modern medicine. Controversy in clinical and experimental data creates the need of performing studies in this direction. The goal of this study is to investigate determining pathogenic mechanisms of thyroid and lactation systems. Realization of the study results will enable development of guidelines for prophylaxis, diagnosis and treatment of mammary gland cancer in patients with thyroid gland malignancy. For this purpose we investigated patients with different types of malignant cancer of thyroid gland (after surgery), who had diffuse fibrocystic mastopathy as a concomitant disorder. Patients underwent conservative therapy only with thyroid agents. We observed patients for 6 months since the beginning of the treatment. During this period patients' condition was evaluated several times using examinations involved in the study. Summarization of study results demonstrated that suppressive therapy might prevent precancerous diseases of mammary gland.


Ribonucleases in HIV type 1 inhibition: effect of recombinant RNases on infection of primary T cells and immune activation-induced RNase gene and protein expression.
Ribonucleases (RNases) have therapeutic potential against cancer and viral diseases and have been reported to inhibit replication of the human immunodeficiency virus type 1 (HIV-1) in chronically infected cell lines. The ribonuclease eosinophil-derived neurotoxin (EDN) is responsible for the anti-HIV-1 activity of a soluble factor produced in response to human alloantigens (ASF). Four recombinant RNases (EDN; a four amino acid extension of the N-terminus EDN, -4EDN; RNase A; and angiogenin) were tested for inhibition of HIV-1 replication in PHA blasts. All RNases showed anti-HIV-1 activity, irrespective of whether the RNases were added before, during, or 2 h after infection. Polyclonal antibodies against the four RNases blocked the antiviral activity. ASF inhibited HIV-1 replication in vitro if added up to 4 h after infection. We demonstrated that allostimulation induced EDN, RNase A, and angiogenin mRNA expression in peripheral blood mononuclear cells (PBMCs), although only EDN protein was detected. We identified monocytes and dendritic cells, but not macrophages or T cells, as EDN-producing cells. These findings raise the possibilities that multiple naturally occurring RNases may contribute to protection against HIV-1 infection and could be considered for utilization in HIV-1 therapy.


Evaluation of surface/interface-related physicochemical and microstructural properties of gelatin 3D scaffolds, and their influence on fibroblast growth and morphology.
This article present new insights in complex relation between surface- and interface-related physicochemical properties and microstructuring of three-dimensional (3D) gelatin scaffolds, being fabricated by simultaneous temperature-controlled freeze-thawing cycle and in situ cross-linking using variable conditions (pH) and molarity of carbodiimide reagents, on the seeding and growth of fibroblast cells with subsequent tracking of their spreading and morphology. Rarely populated cells with rounded morphology and small elongations are observed on negative charge-rich scaffold surface with a lower cross-linking degree (CD), and consequently higher molecular mobility and availability of cell-recognition sequences, in comparison with the prominently elongated and densely populated cells on a positively charged scaffold's surface with higher CD and low mobility. Surface microstructure effect was demonstrated by cell vacuolization and their pure intercommunication being present on scaffold's bottom side with smaller pores (25 ± 19 µm) and pore wall thickness (9 ± 5 µm), over the air-exposed side with twice bigger pores (56 ± 38 µm) and pore wall thicknesses (12 ± 6 µm). Strong correlations of CD (r(2) = 0.96) and local molecular mobility (r(2) = -0.44) with pH and reagents molarity, as well as microstructure features being related to temperature gradient, imply on possibility to modulate scaffold's properties in a direction to guide cell viability and most likely its genotype development.


Transdisciplinary approach: an atypical strategy for improving outcomes in rehabilitative and long-term acute care settings.
In the rehabilitation and long-term acute care settings, an atypical strategy has emerged in the past few years whereby the central focus is on improving patient care through a team approach in which responsibilities are shared and the normal boundaries of the healthcare professions blurred. This article provides a conceptual analysis of this unique, transdisciplinary approach to care delivery. Differentiation between interdisciplinary, multidisciplinary, and transdisciplinary techniques is provided through case scenarios. Defining attributes, necessary antecedents, and the many possible positive outcomes from the transdisciplinary approach to practice is discussed. This concept analysis defines for the rehabilitation or long-term acute care nurse a method that can be used to redesign care delivery, to promote improved patient outcomes, and to achieve a cohesive team environment.


Direct comparison between cerebral oximetry by INVOS(TM) and EQUANOX(TM) during cardiac surgery: a pilot study.
Several near-infrared spectroscopy oximeters are commercially available for clinical use, with lack of standardization among them. Accordingly, cerebral oxygen saturation thresholds for hypoxia/ischemia identified in studies conducted with INVOS(TM) models do not necessarily apply to other devices. In this study, the measurements made with both INVOS(TM) and EQUANOX(TM) oximeters on the forehead of 10 patients during conventional cardiac surgery are directly compared, in order to evaluate the interchangeability of these two devices in clinical practice. Cerebral oxygen saturation measurements were collected from both INVOS(TM) 5100C and EQUANOX(TM) 7600 before anesthetic induction (baseline), two minutes after tracheal intubation, at cardiopulmonary bypass onset/offset, at aortic cross-clamping/unclamping, at the end of surgery and whenever at least one of the two devices measured a reduction in cerebral oxygen saturation equal to or greater than 20% of the baseline value. Bland-Altman analysis was used to compare the bias and limits of agreement between the two devices. A total of 140 paired measurements were recorded. The mean bias between INVOS(TM) and EQUANOX(TM) was -5.1%, and limits of agreement were ±16.37%. Considering the values as percent of baseline, the mean bias was -1.43% and limits of agreement were ±16.47. A proportional bias was observed for both absolute values and changes from baseline. INVOS(TM) and EQUANOX(TM) do not seem to be interchangeable in measuring both absolute values and dynamic changes of cerebral oxygen saturation during cardiac surgery. Large investigations, with appropriate design, are needed in order to identify any device-specific threshold.


Continuum models of focused electron beam induced processing.
Focused electron beam induced processing (FEBIP) is a suite of direct-write, high resolution techniques that enable fabrication and editing of nanostructured materials inside scanning electron microscopes and other focused electron beam (FEB) systems. Here we detail continuum techniques that are used to model FEBIP, and release software that can be used to simulate a wide range of processes reported in the FEBIP literature. These include: (i) etching and deposition performed using precursors that interact with a surface through physisorption and activated chemisorption, (ii) gas mixtures used to perform simultaneous focused electron beam induced etching and deposition (FEBIE and FEBID), and (iii) etch processes that proceed through multiple reaction pathways and generate a number of reaction products at the substrate surface. We also review and release software for Monte Carlo modeling of the precursor gas flux which is needed as an input parameter for continuum FEBIP models.


Identification of significant variation in the composition of lipophosphoglycan-like molecules of E. histolytica and E. dispar.
The lipophosphoglycan-like (LPG-like) molecules of E. histolytica virulent strains are clearly distinct from those of the avirulent E. histolytica and E. dispar strains. Abundant 'LPG' levels are apparently limited to virulent strains, while lipophosphopeptidoglycans ('LPPG's) are common to both virulent and avirulent strains of E. histolytica and E. dispar. It is therefore conceivable that 'LPPG' performs a function that is essential to survival within the host, while the 'LPG' performs a more specific function related to virulence.