Transcriptional activity in diplotene larch microsporocytes, with emphasis on the diffuse stage.
Manuscript provides insights into the biology of long-lived plants, different from Arabidopsis, tomato or grass species that are widely studied. In the European larch the diplotene stage lasts approximately 5 months and it is possible to divide it into several substages and to observe each of them in details. The diplotene stage is a period of intensive microsporocyte growth associated with the synthesis and accumulation of different RNA and proteins. Larch microsporocytes display changes in chromatin morphology during this stage, alternating between 4 short stages of chromatin condensation (contraction) and 5 longer diffusion (relaxation) stages. The occurrence of a diplotene diffusion stage has been observed in many plant species. Interestingly, they have also been observed during spermiogenesis and oogenesis in animals. The aim of this study was to examine whether chromatin relaxation during the diplotene is accompanied by the synthesis and maturation of mRNA. The results reveal a correlation between the diffusion and chromatin decondensation, transcriptional activity. We also found decreasing amount of poly(A) mRNA synthesis in the consecutive diffusion stages. During the early diffusion stages, mRNA is intensively synthesized. In the nuclei large amounts of RNA polymerase II, and high levels of snRNPs were observed. In the late diffusion stages, the synthesized mRNA is not directly subjected to translation but it is stored in the nucleus, and later transported to the cytoplasm and translated. In the last diffusion stage, the level of poly(A) RNA is low, but that of splicing factors is still high. It appears that the mRNA synthesized in early stages is used during the diplotene stage and is not transmitted to dyad and tetrads. In contrast, splicing factors accumulate and are most likely transmitted to the dyad and tetrads, where they are used after the resumption of intense transcription. Similar meiotic process were observed during oogenesis in animals. This indicates the existence of an evolutionarily conserved mechanism of chromatin-based regulation of gene expression during meiotic prophase I.


Video games and youth violence: a prospective analysis in adolescents.
The potential influence of violent video games on youth violence remains an issue of concern for psychologists, policymakers and the general public. Although several prospective studies of video game violence effects have been conducted, none have employed well validated measures of youth violence, nor considered video game violence effects in context with other influences on youth violence such as family environment, peer delinquency, and depressive symptoms. The current study builds upon previous research in a sample of 302 (52.3% female) mostly Hispanic youth. Results indicated that current levels of depressive symptoms were a strong predictor of serious aggression and violence across most outcome measures. Depressive symptoms also interacted with antisocial traits so that antisocial individuals with depressive symptoms were most inclined toward youth violence. Neither video game violence exposure, nor television violence exposure, were prospective predictors of serious acts of youth aggression or violence. These results are put into the context of criminological data on serious acts of violence among youth.


Preventing mediastinal shift after pneumonectomy does not abolish physiological compensation.
To determine the role of mediastinal shift after pneumonectomy (PNX) on compensatory responses, we performed right PNX in adult dogs and replaced the resected lung with a custom-shaped inflatable silicone prosthesis. Prosthesis was inflated (Inf) to prevent mediastinal shift, or deflated (Def), allowing mediastinal shift to occur. Thoracic, lung air, and tissue volumes were measured by computerized tomography scan. Lung diffusing capacities for carbon monoxide (DL(CO)) and its components, membrane diffusing capacity for carbon monoxide (Dm(CO)) and capillary blood volume (Vc), were measured at rest and during exercise by a rebreathing technique. In the Inf group, lung air volume was significantly smaller than in Def group; however, the lung became elongated and expanded by 20% via caudal displacement of the left hemidiaphragm. Consequently, rib cage volume was similar, but total thoracic volume was higher in the Inf group. Extravascular septal tissue volume was not different between groups. At a given pulmonary blood flow, DL(CO) and Dm(CO) were significantly lower in the Inf group, but Vc was similar. In one dog, delayed mediastinal shift occurred 9 mo after PNX; both lung volume and DL(CO) progressively increased over the subsequent 3 mo. We conclude that preventing mediastinal shift after PNX impairs recruitment of diffusing capacity but does not abolish expansion of the remaining lung or the compensatory increase in extravascular septal tissue volume.


Low coherence interferometer for sensing retardance change during neural activity.
A variety of optical measurements, including retardance/birefringence change, have revealed transient optical and structural changes associated with action potential propagation. Those changes can be understood better by developing new techniques and improving the current approaches. To detect transient retardance changes in a stimulated nerve, we propose a differential phase technique utilizing two orthogonal polarization channels of a polarization-maintaining fiber based interferometer. The superior sensitivity of the system (10.4 pm) is promising to achieve a non-contact optical measurement of action potential propagation in reflection mode, and to study the transient retardance changes during neural activity.


LitR, a new transcriptional activator in Vibrio fischeri, regulates luminescence and symbiotic light organ colonization.
Vibrio fischeri is the bacterial symbiont within the light-emitting organ of the sepiolid squid Euprymna scolopes. Upon colonizing juvenile squids, bacterial symbionts grow on host-supplied nutrients, while providing a bioluminescence that the host uses during its nocturnal activities. Mutant bacterial strains that are unable to emit light have been shown to be defective in normal colonization. A 606 bp open reading frame was cloned from V. fischeri that encoded a protein, which we named LitR, that had about 60% identity to four related regulator proteins: Vibrio cholerae HapR, Vibrio harveyi LuxR, Vibrio parahaemolyticus OpaR and Vibrio vulnificus SmcR. When grown in culture, cells of V. fischeri strain PMF8, in which litR was insertionally inactivated, were delayed in the onset of luminescence induction and emitted only about 20% as much light per cell as its parent. Protein-binding studies suggested that LitR enhances quorum sensing by regulating the transcription of the luxR gene. Interestingly, when competed against its parent in mixed inocula, PMF8 became the predominant symbiont present in 83% of light organs. Thus, the litR mutation appears to represent a novel class of mutations in which the loss of a regulatory gene function enhances the bacterium's competence in initiating a benign infection.


Regulation of URG4/URGCP and PPARα gene expressions after retinoic acid treatment in neuroblastoma cells.
Neuroblastoma (NB), originating from neural crest cells, is the most common extracranial tumor of childhood. Retinoic acid (RA) which is the biological active form of vitamin A regulates differentiation of NB cells, and RA derivatives have been used for NB treatment. PPARα (peroxisome proliferator-activated receptor) plays an important role in the oxidation of fatty acids, carcinogenesis, and differentiation. URG4/URGCP gene is a proto-oncogene and that overexpression of URG4/URGCP is associated with metastasis and tumor recurrence in osteosarcoma. It has been known that URG4/URGCP gene is an overexpressed gene in hepatocellular carcinoma and gastric cancers. This study aims to detect gene expression patterns of PPARα and URG4/URGCP genes in SH-SY5Y NB cell line after RA treatment. Expressions levels of PPARα and URG4/URGCP genes were analyzed after RA treatment for reducing differentiation in SH-SY5Y NB cell line. To induce differentiation, the cells were treated with 10 μM RA in the dark for 3-10 days. Gene expression of URG4/URGCP and PPARα genes were presented as the yield of polymerase chain reaction (PCR) products from target genes compared with the yield of PCR products from the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. SH-SY5Y cells possess small processes in an undifferentiated state, and after treatment with RA, the cells developed long neurites, resembling a neuronal phenotype. PPARα gene expression increased in RA-treated groups; URG4/URGCP gene expression decreased in SH-SY5Y cells after RA treatment compared with that in the control cells. NB cell differentiation might associate with PPARα and URG4/URGCP gene expression profile after RA treatment.


Yolk-shell, hollow, and single-crystalline ZnCo(2)O(4) powders: preparation using a simple one-pot process and application in lithium-ion batteries.
The electrochemical properties of yolk-shell-structured, multi-component, transition-metal oxides have not yet been properly compared to those of hollow-structured or nanoscale powders. In this study, yolk-shell, hollow, and single-crystalline ZnCo2 O4 powders with uniform compositions are prepared by using simple gas-phase reaction methods. Double-shelled ZnCo2 O4 yolk-shell powder is prepared directly from the spray solution by using spray pyrolysis. Single-crystalline ZnCo2 O4 nanopowder is prepared by means of flame spray pyrolysis. The yolk-shell ZnCo2 O4 powder shows higher charge and discharge capacities than the hollow and single-crystalline powders. The yolk-shell, hollow, and single-crystalline ZnCo2 O4 powders deliver discharge capacities of 753, 586, and 206 mAh g(-1) , respectively, after 200 cycles at a charge/discharge rate of 3 A g(-1) , and the corresponding capacity retentions measured after the first cycle are 99, 74, and 27 %, respectively. The yolk-shell ZnCo2 O4 powders are structurally stable during cycling and have good electrochemical properties even at high current densities.


Ctf18-RFC and DNA Pol ϵ form a stable leading strand polymerase/clamp loader complex required for normal and perturbed DNA replication.
The eukaryotic replisome must faithfully replicate DNA and cope with replication fork blocks and stalling, while simultaneously promoting sister chromatid cohesion. Ctf18-RFC is an alternative PCNA loader that links all these processes together by an unknown mechanism. Here, we use integrative structural biology combined with yeast genetics and biochemistry to highlight the specific functions that Ctf18-RFC plays within the leading strand machinery via an interaction with the catalytic domain of DNA Pol ϵ. We show that a large and unusually flexible interface enables this interaction to occur constitutively throughout the cell cycle and regardless of whether forks are replicating or stalled. We reveal that, by being anchored to the leading strand polymerase, Ctf18-RFC can rapidly signal fork stalling to activate the S phase checkpoint. Moreover, we demonstrate that, independently of checkpoint signaling or chromosome cohesion, Ctf18-RFC functions in parallel to Chl1 and Mrc1 to protect replication forks and cell viability.


Biologically Analogous Calcium Phosphate Tubes from a Chemical Garden.
Calcium phosphate (CaPO4) tubes with features comparable to mineralized biological microstructures, such as Haversian canals, were grown from a calcium gel/phosphate solution chemical garden system. A significant difference in gel mass in response to high and low solute phosphate equivalent environments existed within 30 min of solution layering upon gel (p = 0.0067), suggesting that the nature of advective movement between gel and solution is dependent on the solution concentration. The transport of calcium cations (Ca2+) and phosphate anions (PO43-) was quantified and changes in pH were monitored to explain the preferential formation of tubes within a PO43- concentration range of 0.5-1.25 M. Ingress from the anionic solution phase into the gel followed by the liberation of Ca2+ ions from the gel was found to be essential for acquiring self-assembled tubular CaPO4 structures. Tube analysis by scanning electron microscopy (SEM), X-ray diffraction (XRD), and micro X-ray florescence (μ-XRF) revealed hydroxyapatite (HA, Ca10(PO4)6(OH)2) and dicalcium phosphate dihydrate (DCPD, CaHPO4·2H2O) phases organized in a hierarchical manner. Notably, the tubule diameters ranged from 100 to 150 μm, an ideal size for the permeation of vasculature in biological hard tissue.


A novel domain in adenovirus L4-100K is required for stable binding and efficient inhibition of human granzyme B: possible interaction with a species-specific exosite.
Lymphocyte granule serine proteases (granzymes) play a critical role in protecting higher organisms against intracellular infections and cellular transformation. The proteases have also been implicated in the generation of tissue damage in a variety of chronic human conditions, including autoimmunity and transplant rejection. Granzyme B (GrB), one cytotoxic member of this family, achieves its effect through cleavage and activation of caspases as well as through caspase-independent proteolysis of cellular substrates. The 100,000-molecular-weight (100K) assembly protein of human adenovirus type 5 (Ad5-100K) was previously defined as a potent and specific inhibitor of human GrB. We now show that although human, mouse, and rat GrB proteases are well conserved in terms of structure, substrate specificity, and function, Ad5-100K inhibitory activity is directed exclusively against the human protease. Biochemical analysis demonstrates that the specificity of the 100K protein for human GrB resides in two distinct interactions with the protease: (i) a unique sequence within the reactive site loop (P(1))Asp(48)-(P(1'))Pro(49) in Ad5-100K which interacts with the active site and (ii) the presence of an additional inhibitor-enzyme interaction likely outside the enzyme catalytic site (i.e., an exosite). We have located this extended macromolecular interaction site in Ad5-100K within amino acids 688 to 781, and we have demonstrated that this region is essential for stable inhibitor-enzyme complex formation as well as efficient inhibition of human GrB. This novel component of the inhibitory mechanism of the 100K protein identifies a distinct target for selective inhibitor design, a finding which may be of benefit for diseases in which GrB plays a pathogenic role.


Body size and risk of epithelial ovarian and related cancers: a population-based case-control study.
Different subtypes of ovarian cancer appear to have different causes; however, the association between body mass index (BMI) and the different subtypes is unclear. We examined the associations between body-mass index (BMI) and weight gain and risk of the different histological subtypes of epithelial ovarian cancer in a case-control study in Australia. Cases aged 18-79 with a new diagnosis of invasive epithelial ovarian cancer (n = 1,269) or borderline tumor (n = 311) were identified through a network of clinics and cancer registries throughout Australia. Controls (n = 1,509) were selected from the Electoral Roll. Height and weight (1 year previously, at age 20 and maximum weight) and other risk factor information were ascertained via a self-administered questionnaire. Obesity was positively associated with clear cell tumors (Odds Ratio 2.3; 95% confidence interval 1.2-4.2) but not invasive endometrioid or mucinous tumors. Although there was no association with invasive serous tumors overall (0.9; 0.7-1.2), we did see an increased risk of serous peritoneal tumors (2.9; 1.7-4.9), but not of serous tumors of the ovary and fallopian tube. Of the borderline subtypes, obesity was positively associated with serous (1.8; 1.1-2.8) but not mucinous tumors (1.1; 0.7-1.7). Overweight was not associated with any subtype overall. There was no association with BMI at age 20, or weight gain for any of the histological subtypes. These results add to the current evidence that obesity increases a woman's risk of developing distinct histological subtypes of ovarian cancer.


C. difficile colitis--predictors of fatal outcome.
Clostridium difficile colitis (CDC) has a clinical spectrum ranging from mild diarrhea to fulminant, potentially fatal colitis. The pathophysiology for this variation remains poorly understood. A total abdominal colectomy may be lifesaving if performed before the point of no return. Identification of negative prognostic factors is desperately needed for optimization of the clinical and operative management. In-patients with CDC between 1999 and 2006 were identified through the discharge database (ICD-9: 008.45). Of these, patients with positive ELISA toxin or biopsy were included. Excluded were ELISA-negative patients. Data collected included general demographics, underlying medical conditions, APACHE II score, clinical and laboratory data, and duration of the medical treatment. Mortality and cure were the two endpoints. Regression analysis was used to identify parameters associated with mortality. Three hundred ninety-eight patients (mean age 59, range 19-94) with CDC were analyzed. Fourteen patients (3.52%) underwent surgery. Mortality in the cohort was 10.3% (41/398 patients). Patients with fatal outcome had a longer pre-CDC hospital stay (11 vs. 6 days). Mortality was significantly (p<0.05) associated with a higher APACHE II score, a higher ASA class, a lower diastolic blood pressure, preexisting pulmonary and renal disease, use of steroids, evidence of toxic megacolon, higher WBCs, and clinical signs of sepsis and organ dysfunction (renal and pulmonary). Parameters without significant difference (p>0.05) included patient age, albumin, clinical presentation/examination parameters, and transplant status, other than the mentioned comorbidities. Of the 41 fatal outcomes, five patients (12.2%) underwent surgery, and 36 did not (87.8%). Mortality rate of the surgical group was 35.7% (four out of 14 patients). Comparison of the fatalities not undergoing surgery with the survivors revealed decreased clinical signs, suggesting a masking of the disease severity. Our study identified several clinical factors, which were associated with mortality from CDC. Future clinical studies will have to focus on the disease progression and the fatalities occurring either without an attempt for or despite surgical intervention, as an earlier intervention might have proven lifesaving.


Multigene analyses of bilaterian animals corroborate the monophyly of Ecdysozoa, Lophotrochozoa, and Protostomia.
Almost a decade ago, a new phylogeny of bilaterian animals was inferred from small-subunit ribosomal RNA (rRNA) that claimed the monophyly of two major groups of protostome animals: Ecdysozoa (e.g., arthropods, nematodes, onychophorans, and tardigrades) and Lophotrochozoa (e.g., annelids, molluscs, platyhelminths, brachiopods, and rotifers). However, it received little additional support. In fact, several multigene analyses strongly argued against this new phylogeny. These latter studies were based on a large amount of sequence data and therefore showed an apparently strong statistical support. Yet, they covered only a few taxa (those for which complete genomes were available), making systematic artifacts of tree reconstruction more probable. Here we expand this sparse taxonomic sampling and analyze a large data set (146 genes, 35,371 positions) from a diverse sample of animals (35 species). Our study demonstrates that the incongruences observed between rRNA and multigene analyses were indeed due to long-branch attraction artifacts, illustrating the enormous impact of systematic biases on phylogenomic studies. A refined analysis of our data set excluding the most biased genes provides strong support in favor of the new animal phylogeny and in addition suggests that urochordates are more closely related to vertebrates than are cephalochordates. These findings have important implications for the interpretation of morphological and genomic data.


p53 induction and apoptosis in response to radio- and chemotherapy in vivo is tumor-type-dependent.
The p53 protein rapidly accumulates in cells in response to DNA damage, which can trigger apoptosis. This pathway is hypothesized to be important for tumor suppression by p53, as well as for the response of tumors to chemo- or radiotherapy. Implicit in these ideas is that the p53 induction-apoptosis pathway is active in tumor cells in vivo. Because tumor suppression by p53 in mice is markedly tissue-type-dependent, we tested the activity of the pathway in tumors in vivo by inducing tumors in six different tissues and treating tumor-bearing mice with DNA damaging cancer therapeutic agents. In response to treatment, cells from T-cell lymphomas, intestinal adenomas, and mammary tumors rapidly induced p53 and underwent apoptosis. In squamous cell papillomas, p53 was constitutively expressed and was further induced by the treatments, but apoptotic cells were only rarely observed. In treated mice bearing lung or liver adenomas, minimal or no p53 accumulation or apoptosis was observed in the tumor cells. Thus, there is marked variation in the intrinsic ability of autochthonous tumor cells to accumulate p53 and undergo apoptosis. This variation provides one explanation for the tissue specificity of tumor suppression by p53. It also indicates that the role of apoptosis in the response of tumors to therapy varies significantly among tumor types.


Latitudinal variation of freeze tolerance in intertidal marine snails of the genus Melampus (Gastropoda: Ellobiidae).
Abstract Low temperatures limit the poleward distribution of many species such that the expansion of geographic range can only be accomplished via evolutionary innovation. We have tested for physiological differences among closely related species to determine whether their poleward latitudinal ranges are limited by tolerance to cold. We measured lower temperature tolerance (LT50) among a group of intertidal pulmonate snails from six congeneric species and nine locales. Differences in tolerance are placed in the context of a molecular phylogeny based on one mitochondrial (cytochrome oxidase subunit I) and two nuclear (histone 3 and a mitochondrial phosphate carrier protein) markers. Temperate species from two separate lineages had significantly lower measures of LT50 than related tropical species. Range differences within the temperate zone, however, were not explained by LT50. These results show that multiple adaptations to cold and freezing may have enabled range expansions out of the tropics in Melampus. However, northern range limits within temperate species are not governed by cold tolerance alone.


KCNC3: phenotype, mutations, channel biophysics-a study of 260 familial ataxia patients.
We recently identified KCNC3, encoding the Kv3.3 voltage-gated potassium channel, as the gene mutated in SCA13. One g.10684G>A (p.Arg420His) mutation caused late-onset ataxia resulting in a nonfunctional channel subunit with dominant-negative properties. A French early-onset pedigree with mild mental retardation segregated a g.10767T>C (p.Phe448Leu) mutation. This mutation changed the relative stability of the channel's open conformation. Coding exons were amplified and sequenced in 260 autosomal-dominant ataxia index cases of European descent. Functional analyses were performed using expression in Xenopus oocytes. The previously identified p.Arg420His mutation occurred in three families with late-onset ataxia. A novel mutation g.10693G>A (p.Arg423His) was identified in two families with early-onset. In one pedigree, a novel g.10522G>A (p.Arg366His) sequence variant was seen in one index case but did not segregate with affected status in the respective family. In a heterologous expression system, the p.Arg423His mutation exhibited dominant-negative properties. The p.Arg420His mutation, which results in a nonfunctional channel subunit, was recurrent and associated with late-onset progressive ataxia. In two families the p.Arg423His mutation was associated with early-onset slow-progressive ataxia. Despite a phenotype reminiscent of the p.Phe448Leu mutation, segregating in a large early-onset French pedigree, the p.Arg423His mutation resulted in a nonfunctional subunit with a strong dominant-negative effect.


Stable Flatbands, Topology, and Superconductivity of Magic Honeycomb Networks.
We propose a new principle to realize flatbands which are robust in real materials, based on a network superstructure of one-dimensional segments. This mechanism is naturally realized in the nearly commensurate charge-density wave of 1T-TaS_{2} with the honeycomb network of conducting domain walls, and the resulting flatband can naturally explain the enhanced superconductivity. We also show that corner states, which are a hallmark of the higher-order topological insulators, appear in the network superstructure.


Cancer among the circumpolar Inuit, 1989-2003. I. Background and methods.
This is first of 2 papers on the Circumpolar Inuit Cancer Review, an international collaborative effort involving researchers and health officials from Alaska, Canada and Greenland. It covers the period 1989-2003, updating the last review (1969-1988) and together provides an overview of the trends and patterns of cancer among the Inuit in 3 countries and over a 35-year period. Inuit cancer cases by age-sex group and anatomic site were obtained from the regional cancer registries. The sources of the age-sex distribution of various Inuit populations include the population registry (Greenland), and annual estimates and periodic censuses (Alaska and Canada). Incidence rates were age-standardization by the direct method to the standard world population of the International Agency for Research on Cancer. This project demonstrates the feasibility of international partnerships in cancer surveillance, and when these partnerships are extended to other diseases and health conditions, they can contribute to the development of a Circumpolar Health Observatory.


Close relationship between autoimmune pancreatitis and multifocal fibrosclerosis.
Autoimmune pancreatitis is a unique clinical entity proposed recently, and is sometimes associated with inflammation of other organs. To examine the pathophysiology of the pancreas and other organs in patients with autoimmune pancreatitis. We evaluated clinicopathological findings in six resected and one autopsied patient with autoimmune pancreatitis. The pancreas, peripancreatic tissue, bile duct, and gall bladder were examined histologically and immunohistochemically. Biopsied salivary gland and cervical lymph node of one patient were also examined. We also performed similar immunohistochemical examinations in pancreatectomy specimens from 10 patients with alcoholic chronic pancreatitis and biopsied salivary glands from five patients with Sjögren's syndrome. Stenosis of the extrahepatic bile duct was detected in all patients. Histological findings were characterised by diffuse lymphoplasmacytic infiltration with marked interstitial fibrosis and acinar atrophy, obliterated phlebitis of the pancreatic veins, and involvement of the portal vein. Immunohistochemically, diffusely infiltrating cells consisted predominantly of CD4 or CD8 positive T lymphocytes and IgG4 positive plasma cells. Similar inflammatory processes also involved the peripancreatic tissue, extrahepatic bile duct, gall bladder, and salivary gland. Lymph nodes were swollen with infiltration of IgG4 positive plasma cells. None of these findings was seen in alcoholic chronic pancreatitis or Sjögren's syndrome. The development of the specific inflammations in extensive organs as well as the pancreas in patients with autoimmune pancreatitis strongly suggests a close relationship between autoimmune pancreatitis and multifocal fibrosclerosis.


Dynamics and ethics of comprehensive preimplantation genetic testing: a review of the challenges.
Genetic testing of preimplantation embryos has been used for preimplantation genetic diagnosis (PGD) and preimplantation genetic screening (PGS). Microarray technology is being introduced in both these contexts, and whole genome sequencing of blastomeres is also expeted to become possible soon. The amount of extra information such tests will yield may prove to be beneficial for embryo selection, will also raise various ethical issues. We present an overview of the developments and an agenda-setting exploration of the ethical issues. The paper is a joint endeavour by the presenters at an explorative 'campus meeting' organized by the European Society of Human Reproduction and Embryology in cooperation with the department of Health, Ethics & Society of the Maastricht University (The Netherlands). The increasing amount and detail of information that new screening techniques such as microarrays and whole genome sequencing offer does not automatically coincide with an increasing understanding of the prospects of an embryo. From a technical point of view, the future of comprehensive embryo testing may go together with developments in preconception carrier screening. From an ethical point of view, the increasing complexity and amount of information yielded by comprehensive testing techniques will lead to challenges to the principle of reproductive autonomy and the right of the child to an open future, and may imply a possible larger responsibility of the clinician towards the welfare of the future child. Combinations of preconception carrier testing and embryo testing may solve some of these ethical questions but could introduce others. As comprehensive testing techniques are entering the IVF clinic, there is a need for a thorough rethinking of traditional ethical paradigms regarding medically assisted reproduction.


Intracoronary ECG ST-segment recovery during primary percutaneous intervention for ST-segment myocardial infarction: insights from a cardiac MRI study.
ST-segment-resolution (STR) on surface electrocardiogram (ECG) is a good surrogate for myocardial reperfusion in patients with acute ST-segment-elevation-myocardial-infarction (STEMI). We sort to determine the optimal criteria of measuring STR on intracoronary-ECG (IC-ECG) for prediction of myocardial injury evaluated by cardiac MRI (CMR). Measurements of IC-ECG ST-segments were performed at baseline, immediately after (early) and 15 min (late) after achieving TIMI-3 flow during primary-PCI. The degree of ST-segment-shift from baseline noted upon the IC-ECG was divided into four groups: (group 1) ST-segment-resolution >1 mm, (group 2) <30% resolution, (group 3) >50% resolution, (group 4) >70% resolution at both early and late time points. Patients had CMR at days 3 and 90 postprimary-PCI. Fifty two patients (aged 60 ± 11 years; 43 males) were evaluated. Early intracoronary-ECG ST-segment resolution (early IC-STR >1 mm) correlated with smaller scar mass (P = 0.003), nonviable myocardial mass (P < 0.001), and microvascular obstruction (MVO) (P = 0.004) on CMR at day 3. Ejection fraction (EF) was also better at day 3 (P = 0.026) and 90 (P = 0.039). Patients with poor early IC-STR (IC-STR <30%) conversely is associated with larger scar mass (P = 0.017), nonviable myocardial mass (P = 0.01), and MVO (P = 0.021) at day 3. This was also associated with worse EF at day 90 (P = 0.044). Neither group 3 or 4, or the late measurements of late IC-STR correlated with CMR markers of myocardial injury. The degree of early IC-STR (defined by IC-STR > 1 mm or <30%) successfully predicts myocardial damage following primary-PCI for an acute STEMI. Further studies are required to investigate its potential utility.


Intercellular trafficking of transcription factors in the vascular tissue patterning.
Throughout life cycles, plants grow in an indeterminate manner by adding new cells and organs with specialized functions. Newly emerging cells acquire their identities depending on their positions relative to the neighboring cells. Exchanging positional signals between cells is critical in this process. Recent studies showed that many transcription factors move between cells or between organs in forms of proteins and messenger RNA (mRNA). Some of these were found to be important positional signals for cell type patterning. Cell type patterning in the vascular system is no exception from this. In this review, we describe recent discoveries of mobile transcription factors that function as positional signals for vascular tissue patterning and propose how these transcription factors integrate with other forms of signals.


Spatio-temporal gait characteristics of level and vertical locomotion in a ground-dwelling and a climbing gecko.
The effects of incline (vertical versus horizontal) on spatio-temporal gait characteristics (stride and step length, frequency, duty factor, degree of sprawling) were measured over a range of speeds in a ground-dwelling (Eublepharis macularius) and a climbing (Gekko gecko) species of gecko. Surprisingly, the climbing species also performs very well when moving on the horizontal substratum. In the present experiments, climbing speeds ranged from 0.6 to 1.2 m s(-1), whereas speeds for level locomotion were between 0.6 and 1.8 m s(-1). In contrast, the vertical climbing capacities of the ground-dweller are limited (speeds below 0.1 m s(-1 )versus level speeds between 0.2 and 1.1 m s(-1)). In general, we demonstrate that very little adjustment in gait characteristics is made by either species when they are forced to move on their non-habitual substratum. Moreover, gait characteristics differ little between the species despite the clear differences in ecological niche. Higher level or climbing speeds are realized mainly (or exclusively in the case of level locomotion in G. gecko) by increasing stride frequency. Stride lengths and duty factors vary with speed in the ground-dweller, but not in the climbing species. Step length and the degree of sprawling are speed-independent (except for hind-limb sprawling in G. gecko on the level). It is argued that this common strategy suits climbing (fixed spatial variables, no floating phases) rather than level locomotion.


Analysis of individual platelet-derived microparticles, comparing flow cytometry and capillary electrophoresis with laser-induced fluorescence detection.
Platelet-derived microparticles (PMPs) formed by vesiculation during platelet activation seem to play a role in blood coagulation and in pathological disease states. Flow cytometry is currently the gold standard to characterize platelets and PMPs. Using this technique we distinguished between platelets and PMPs based on size and the presence of phosphatidyl serine (PS); PMPs were arbitrarily defined to be smaller than one micrometer and capable of forming a stable complex with fluorescently-labeled Annexin V, a protein that forms a calcium-dependent complex with PS. Further confirmation of PMP and platelet identity was done by use of fluorescently-labeled antibodies against CD41a, a glycoprotein found on the surface of both platelets and PMPs. In this report we also introduce the use of capillary electrophoresis with post-column laser-induced fluorescence detection (CE-LIF) for the analysis of fluorescently labeled platelets and PMPs. While both flow cytometry and CE-LIF can measure individual fluorescent events, only CE-LIF allowed us to calculate individual electrophoretic mobilities of activated platelets and PMPs that were then represented as distributions. A comparison between distributions suggests that PMPs have less negative mobilities. The fact that activated platelet preparations include PMPs partially obscure the interpretation of the data. While PMP and platelet number ml(-1) determined by flow cytometry is lower than the same parameter determined by CE-LIF, signal-to-noise ratio was 20 fold better for flow cytometry than for CE-LIF. This is the first time that a direct comparison between these two techniques is reported.


Effects of Surface Protein Adsorption on the Distribution and Retention of Intratumorally Administered Gold Nanoparticles.
The heterogeneous distribution of delivery or treatment modalities within the tumor mass is a crucial limiting factor for a vast range of theranostic applications. Understanding the interactions between a nanomaterial and the tumor microenvironment will help to overcome challenges associated with tumor heterogeneity, as well as the clinical translation of nanotheranostic materials. This study aims to evaluate the influence of protein surface adsorption on gold nanoparticle (GNP) biodistribution using high-resolution computed tomography (CT) preclinical imaging in C57BL/6 mice harboring Lewis lung carcinoma (LLC) tumors. LLC provides a valuable model for study due to its highly heterogenous nature, which makes drug delivery to the tumor challenging. By controlling the adsorption of proteins on the GNP surface, we hypothesize that we can influence the intratumoral distribution pattern and particle retention. We performed an in vitro study to evaluate the uptake of GNPs by LLC cells and an in vivo study to assess and quantify the GNP biodistribution by injecting concentrated GNPs citrate-stabilized or passivated with bovine serum albumin (BSA) intratumorally into LLC solid tumors. Quantitative CT and inductively coupled plasma optical emission spectrometry (ICP-OES) results both confirm the presence of particles in the tumor 9 days post-injection (n = 8 mice/group). A significant difference is highlighted between citrate-GNP and BSA-GNP groups (** p < 0.005, Tukey's multiple comparisons test), confirming that the protein corona of GNPs modifies intratumoral distribution and retention of the particles. In conclusion, our investigations show that the surface passivation of GNPs influences the mechanism of cellular uptake and intratumoral distribution in vivo, highlighting the spatial heterogeneity of the solid tumor.


Comprehensive assessment of the slice sensitivity profiles in breast tomosynthesis and breast CT.
This study experimentally evaluated the slice sensitivity profile (SSP) and its relationship between acquisition angle, object size, and cone angle. The sensitivity profile metric was used to characterize a breast tomosynthesis system's resolution in the z-axis. The SSP was also measured on a prototype breast computed tomography (bCT) system. The SSP was measured using brass disks placed within adipose tissue-equivalent breast phantoms. The digital tomosynthesis system (Selenia Dimensions, Hologic Corporation, Bedford, MA) acquires projection images over a 15° angular range and the bCT scanner acquires projection images over a 360° angular range. Angular ranges between 15° and 360° were studied by using a subset of the projection images acquired on the bCT scanner. The SSP was determined by measuring a background-corrected mean gray scale value as a function of the z-position (axis normal to the plane of the detector). The results show that SSP improves when the angular acquisition range is increased and the SSP approaches a delta function for angles greater than 180°. Smaller objects have a narrower SSP and the SSP is not significantly dependent on the cone angle. For a 2.5, 5, 10 mm disk, the full width at half maximum of the SSP was 35, 61, 115 mm, respectively, on the tomosynthesis system (at 15°) and was 0.5 mm for all disk diameters on the bCT scanner (at 360°). The SSP is dependent on object size and angular acquisition range. These dependencies are overcome once the angular acquisition range is increased beyond 180°.


The elusive meningococcal meningitis serogroup: a systematic review of serogroup B epidemiology.
Invasive meningococcal disease (IMD), is a widely distributed, complex human disease affecting all age categories. The causative agent, Neisseria meningitidis, is spread through aerosol respiratory droplets. 13 different serogroups have been identified, each with varying epidemiological features including prevalence, virulence, immunogenicity, geographical and temporal distribution. Although preventative measures are available for several of the serogroups, meningococcal disease caused by serogroup B is of particular interest due to the challenge it presents concerning vaccine development. A systematic review of peer reviewed studies and reports, the collection of data from national and international health resources, along with the analysis of the Multi Locus Sequence Typing database was carried out aimed at collecting information concerning serogroup B IMD and the epidemiology attached to it. A continuous output of related and novel STs occurring worldwide in terms of the hypervirulent clonal complexes was observed both in published studies and the MLST database in this case using the eburst software, which highlights the genetically diverse nature of serogroup B strains. With the recent dominance of serogroup B IMD seen in many countries, along with the presence of antibiotic resistance, vaccine development needs to target areas of the bacterium which tackle this widespread and heterogeneous aspect of meningococcal meningitis disease.


Hyperthermia promotes the incidence of tumours following X-irradiation of the rat cervical cord region.
The cervical region of the rat, including the spinal cord (cervical 5-thoracic 2) was irradiated with single doses of 15-32 Gy 250 kV X-rays. Hyperthermia, at temperatures of 42-, 43- and 44 +/- 0.1 degrees C for 30 min was applied to the cervical vertebral column and immediate adjacent tissues for 5-10 min or 7 h after X-irradiation. Over a period of 18-21 months, animals were followed up to monitor neurological complications occurring as a result of damage to the spinal cord (Sminia et al. 1991). We also noted the development of neoplasms either inside or outside the cervical region. The data on tumour incidence were analysed retrospectively using the actuarial method. Although hyperthermia alone was not carcinogenic, it led to a significant increase of radiation-induced tumours. This increase of radiation carcinogenesis was observed both with hyperthermia applied 5-10 min after X-rays and with an interval of 7 h between X-rays and heat. Cancer induction was highest after the lower radiation doses (16 Gy) combined with high heat doses (30 min 44 degrees C). The latent period for induction of tumours by X-rays was 472 +/- 19 days (mean +/- SEM; n = 24). Latency was significantly shortened by hyperthermia to 404 +/- 34 days (n = 22) if applied 5-10 min after X-rays and to 348 +/- 6 days (n = 33) with an interval of 7 h. Histology revealed that 86% (38/44) of the examined tumours found inside the volume treated with hyperthermia and irradiation were sarcomas. The percentage of animals with a tumour outside the treated volume was almost the same for all treatment groups. Most of these tumours were of the mammary gland type.


Voluntary consent in correctional settings: do offenders feel coerced to participate in research?
A major ethical concern in research with criminal offenders is the potential for abuse due to coercive influences that may adversely affect offenders' capacity to give voluntary consent to participate in research conducted in correctional settings. Despite this concern, to date there have been almost no systematic scientific investigations of the extent to which offenders themselves perceive that coercion occurs in these settings or that it is likely to influence their decisions about research participation. In a sample of over 600 ethnically diverse men and women recruited from various prisons and community corrections facilities in Texas and Florida, we used a vignette-based survey concerning a hypothetical research project to measure and compare offenders' global perceptions of coercive processes, as well as the differential salience and perceived coercive influence of specific factors (e.g., coercion by other inmates, inducements from staff). Somewhat surprisingly, across multiple outcome measures our participants on average reported relatively little in the way of significant coercive influences on their capacity to make voluntary decisions concerning research participation. Implications and directions for future research on coercive influences in offender research are discussed.


[Effect of the cultivation temperature on gramicidin S biosynthesis under conditions of producer growth limitation by oxygen].
The gramicidin S-producing organisms Bacillus brevis was grown under submerged conditions in fermenters at a temperature of 32 degrees C which is the lower limit of the temperature ranges providing the culture growth. The culture was also grown under the optimal temperature conditions, i.e. 40 degrees C. At the lower temperature the biomass synthesis at the early stage of the culture development was decreased, the intensity of the cell respiration was low and solubility of oxygen in the liquid was increased. Under such conditions the decrease in the levels of dissolved oxygen in the medium was less pronounced than that under the control conditions. At the lower temperature limitation of the culture growth by the deficit of dissolved oxygen lowered and the period of the antibiotic synthesis increased which brought about a rise of the gramicidin S yield by 30-40 per cent.


Salivary resistin reflects local inflammation in Sjögren's syndrome.
To assess the role of resistin in primary Sjögren's syndrome (pSS) and its relation to local inflammation. Blood and saliva were collected from 37 patients with pSS (duration of symptoms 12.6+/-1 yrs) and 32 healthy controls. Expression of resistin in salivary glands was visualized immunohistologically, and levels of resistin were detected by ELISA. Levels of resistin were evaluated at baseline and following oral dehydroepiandrosterone (DHEA) treatment (50 mg/day). The effect of DHEA treatment on the secretion of resistin was assessed in vitro in human leukocytes after challenge with insulin and lipopolysaccharide. Levels of resistin in saliva were significantly higher in patients with pSS than in controls, while circulating levels of resistin were similar in both groups. Resistin was expressed in the epithelial cells of striated ducts and in the lymphocytic foci. Resistin levels in saliva were related to the intensity of inflammation in the minor salivary glands of pSS patients. No changes of the levels of resistin in blood or saliva were observed during DHEA treatment. Exposure of naive leukocytes to DHEA in vitro induced significant expression of resistin compared to nonstimulated peripheral blood mononuclear cells (p=0.031). We showed that levels of resistin are upregulated locally in the salivary glands of patients with pSS; and that the levels of resistin correspond to the intensity of lymphocytic inflammation in patients with pSS. We suggest that resistin is expressed in the salivary glands of patients with pSS and may be a driving factor of local inflammation.


Ramadan and sport: minimizing effects upon the observant athlete.
The intermittent fasting of Ramadan could affect various aspects of body physiology and biochemistry important to athletic success. Much of the available information on this subject has been collected from sedentary subjects or low-level competitors, often without well matched controls. Other issues requiring clearer definition include the duration of fasting, the local environment, the timing of observations, and changes in training, diet and sleep patterns. Sleep may be shortened or made good with daytime naps. Circadian rhythms of temperature, metabolism, hormonal secretions and physical performance may be disrupted and incidental activities curtailed. Disturbances of psychomotor performance include daytime sleepiness, impaired vigilance and slower reactions. Food intake is limited to night-time meals. Sedentary individuals sometimes exploit Ramadan to reduce body fat stores. Well disciplined athletes usually maintain energy balance unless daily energy expenditures are very high. Protein intake must allow for gluconeogenesis, and provide quality protein ingested around training times. Blood sugar levels are likely to fall over a long and active day, even if morning glycogen reserves are maximized. Metabolism of fat should be encouraged, beginning prior to Ramadan; inclusion of fat in the pre-dawn meal also slows gastric emptying. Daytime fluid depletion is inevitable if athletes exercise in the heat, but the immediate deficit can usually be made good at night. Some studies show an initial fluid depletion, with recovery as Ramadan continues, possibly reflecting changes in urine and sweat production. Top athletes can maintain training throughout Ramadan, although coaches sometimes reduce demands through a pre-competitive tapering of effort. Late night or early morning training requires negotiation with players who are not observing Ramadan, and dietary adjustments to maintain optimal plasma amino acid levels when training. Performance of repeated anaerobic exercise is impaired, but aerobic power and muscular strength show little change during Ramadan. Ratings of fatigue are increased, and vigilance and reaction times are impaired, particularly during the afternoon. Medical issues during Ramadan are few. Athletes with diabetes mellitus should seek a medical exemption from fasting, and prescribed drug schedules should be carefully maintained. There is no major increase of injury rates, but competitors may have difficulty in producing urine for doping controls. Logical measures to minimize the effects of Ramadan include the optimization of mood state, maintenance of training, minimization of sleep loss, appropriate adjustments of diet, and the monitoring of competitors for chronic dehydration. Future research should concentrate on the changes observed in top athletes, particularly women, with data collected in the late afternoon after a known period of fasting in a well defined environment. It will be important to ensure that the lifestyle of those studied has been optimized. Implications of chronic dehydration for doping control also merit further investigation. Current data suggest that the impact of Ramadan upon athletic performance is small relative to the precision of test procedures, although it may be sufficient to cause a loss of medals. Negative effects vary widely with the type of sport, the season when fasting is observed, the local culture and the discipline exercised by the athlete.


Diesel exhaust inhalation and assessment of peripheral blood mononuclear cell gene transcription effects: an exploratory study of healthy human volunteers.
Ambient fine particulate matter has been associated with cardiovascular and other diseases in epidemiological studies, and diesel exhaust (DE) is a major source of urban fine particulate matter. Air pollution's cardiovascular effects have been attributed to oxidative stress and systemic inflammation, with resulting perturbation of vascular homeostasis. Peripheral leukocytes are involved in both inflammation and control of vascular homeostasis. We conducted a pilot study using microarray techniques to analyze whether global gene expression profiles in peripheral blood mononuclear cells (PBMCs) can elucidate effects of DE inhalation, for further investigation of mechanisms underlying vascular effects. In a double-blind, crossover, controlled exposure study, healthy adult volunteers were exposed in randomized order to filtered air (FA) and diluted DE in 2-h sessions. We isolated RNA (Trizol/Qiagen method) from PBMCs before and two times after each exposure. RNA samples were arrayed using the Affymetrix U133 Plus 2.0 arrays. Microarray analyses were conducted on five subjects with available RNA samples from exposures to FA and to the highest DE inhalation (200 microg/m(3) of fine particulate matter). Following data normalization and statistical analysis, a total of 1290 out of 54,675 probe sets evidenced differential expression (more than 1.5-fold up- or downregulated with p < .05) between FA and DE exposure. These genes demonstrated a clear distinction between the FA and DE groups and an indication of a time-dependent effect on biological processes such as inflammation and oxidative stress. This study addresses the value of using PBMC gene expression to assess pathways relevant to cardiovascular effect in healthy individuals.


Effect of full-time versus part-time school nurses on attendance of elementary students with asthma.
Asthma, the most common chronic disease in children today, is the leading cause of absenteeism among students. It accounts for nearly 20 million lost school days annually. This study examined whether full-time (5 days per week) or part-time (2 days per week) school nurses would have a differential effect on the frequency of absences among elementary school students with asthma. This study found that students with asthma who were poor or who were African American and in schools with full-time nurses missed significantly fewer days (3 days, or 23% fewer missed days) than did their counterparts with asthma in schools with part-time nurses.


Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials.
To analyze recurrence patterns in patients with cancer of the esophagus or gastroesophageal junction treated with either preoperative chemoradiotherapy (CRT) plus surgery or surgery alone. Recurrence pattern was analyzed in patients from the previously published CROSS I and II trials in relation to radiation target volumes. CRT consisted of five weekly courses of paclitaxel and carboplatin combined with a concurrent radiation dose of 41.4 Gy in 1.8-Gy fractions to the tumor and pathologic lymph nodes with margin. Of the 422 patients included from 2001 to 2008, 418 were available for analysis. Histology was mostly adenocarcinoma (75%). Of the 374 patients who underwent resection, 86% were allocated to surgery and 92% to CRT plus surgery. On January 1, 2011, after a minimum follow-up of 24 months (median, 45 months), the overall recurrence rate in the surgery arm was 58% versus 35% in the CRT plus surgery arm. Preoperative CRT reduced locoregional recurrence (LRR) from 34% to 14% (P < .001) and peritoneal carcinomatosis from 14% to 4% (P < .001). There was a small but significant effect on hematogenous dissemination in favor of the CRT group (35% v 29%; P = .025). LRR occurred in 5% within the target volume, in 2% in the margins, and in 6% outside the radiation target volume. In 1%, the exact site in relation to the target volume was unclear. Only 1% had an isolated infield recurrence after CRT plus surgery. Preoperative CRT in patients with esophageal cancer reduced LRR and peritoneal carcinomatosis. Recurrence within the radiation target volume occurred in only 5%, mostly combined with outfield failures.


Sentinel Node and Ovarian Tumors: A Series of 20 Patients.
Intraoperative detection of ovarian sentinel nodes has been shown to be feasible. We examined the detection rate and locations of sentinel nodes in patients with ovarian tumors. We also aimed to assess the reliability of sentinel node method in predicting regional lymph node metastasis. Twenty patients scheduled for laparotomy because of a pelvic mass were recruited to the study. In the beginning of the laparotomy, radioisotope and blue dye were injected under the serosa next to the junction of the ovarian tumor and suspensory ligament. The number and locations of the hot and/or blue nodes/spots were recorded during the operation. If the tumor was malignant according to the frozen section, systematic lymphadenectomies were performed, the sentinel nodes sampled separately, and their status compared with other regional lymph nodes. Eleven patients had a right-sided ovarian tumor, 7 patients a left-sided tumor, and 2 patients had bilateral tumors. A median of 2 sentinel nodes/locations per patient (range, 1-3) were found. Sixty percent of all sentinel nodes were located in the para-aortic region only, compared with 30% in both para-aortic and pelvic areas and 10% in pelvic area only. Both unilateral and bilateral locations were found. In 83% of the cases with more than 1 sentinel node location, they were located in separate anatomical regions. In 3 patients, systematic lymphadenectomies were performed. One of them had nodal metastases in 2 regions and also a metastasis in 1 of her 2 sentinel nodes in 1 of those regions. In patients with ovarian tumor(s), the detection of sentinel nodes is feasible. They are located in different anatomic areas both ipsilaterally and contralaterally, although most of them are found in the para-aortic region. The reliability of the sentinel node concept should be evaluated in the framework of a multicenter trial.


Proteomic profiles of mouse neuro N2a cells infected with variant virulence of rabies viruses.
We characterized the proteomes of murine N2a cells following infection with three rabies virus (RV) strains, characterized by distinct virulence phenotypes (i.e., virulent BD06, fixed CVS-11, and attenuated SRV9 strains), and identified 35 changes to protein expression using two-dimensional gel electrophoresis in whole-cell lysates. The annotated functions of these proteins are involved in various cytoskeletal, signal transduction, stress response, and metabolic processes. Specifically, a-enolase, prx-4, vimentin, cytokine-induced apoptosis inhibitor 1 (CIAPIN1) and prx-6 were significantly up-regulated, whereas Trx like-1 and galectin-1 were down-regulated following infection of N2a cells with all three rabies virus strains. However, comparing expressions of all 35 proteins affected between BD06-, CVS-11-, and SRV9-infected cells, specific changes in expression were also observed. The up-regulation of vimentin, CIAPIN1, prx-4, and 14-3-3 theta/delta, and downregulation of NDPK-B and HSP-1 with CVS and SRV9 infection were ≥ 2 times greater than with BD06. Meanwhile, Zfp12 protein, splicing factor, and arginine/serine-rich 1 were unaltered in the cells infected with BD06 and CVS- 11, but were up-regulated in the group infected with SRV9. The proteomic alterations described here may suggest that these changes to protein expression correlate with the rabies virus' adaptability and virulence in N2a cells, and hence provides new clues as to the response of N2a host cells to rabies virus infections, and may also aid in uncovering new pathways in these cells that are involved in rabies infections. Further characterization of the functions of the affected proteins may contribute to our understanding of the mechanisms of RV infection and pathogenesis.


Recent advances in surface functionalization techniques on polymethacrylate materials for optical biosensor applications.
Biosensor chips for immune-based assay systems have been investigated for their application in early diagnostics. The development of such systems strongly depends on the effective protein immobilization on polymer substrates. In order to achieve this complex heterogeneous interaction the polymer surface must be functionalized with chemical groups that are reactive towards proteins in a way that surface functional groups (such as carboxyl, -COOH; amine, -NH2; and hydroxyl, -OH) chemically or physically anchor the proteins to the polymer platform. Since the proteins are very sensitive towards their environment and can easily lose their activity when brought in close proximity to the solid surface, effective surface functionalization and high level of control over surface chemistry present the most important steps in the fabrication of biosensors. This paper reviews recent developments in surface functionalization and preparation of polymethacrylates for protein immobilization. Due to their versatility and cost effectiveness, this particular group of plastic polymers is widely used both in research and in industry.


Variation in the prevalence of gastric cancer in Perú.
Most cases of gastric cancers occur in non-industrialized countries but there is scarce information about the epidemiology of this illness in these countries. Our study examined whether there was a variation in the prevalence of gastric cancer in Lima, Perú over the last 2 decades. Subjects older than 29 years of age were included. They underwent an esophagogastroduedonoscopy at 3 socioeconomically different health facilities in Lima: a county hospital (7,168 subjects), a Peruvian-Japanese Clinic (14,794 individuals) and a private hospital (4,893 individuals). Birth cohort prevalence of gastric cancer was used. Regression models were calculated to predict the future prevalence of gastric cancer. It was found that the birth cohort prevalence of gastric cancer decreased in Perú from 22.7 to 2% (p < 0.001), from 12 to 0.5% (p < 0.001), and from 6.5 to 0.1% (p < 0.001) in the low, middle and high socioeconomic group, respectively. The prevalence of intestinal metaplasia decreased from 44.3 to 12.5% (p < 0.001), from 28.4 to 5% (p < 0.001), and from 19.4 to 2.2% (p < 0.001) in the low, middle and high socioeconomic status, respectively. These trends will likely persist over the future decades. Nevertheless, the prevalence of gastric cancer remains high in subjects older than 59 years of age in the low socioeconomic status. It is concluded that the prevalence of gastric cancer is decreasing in Perú, similar to the current trend undergoing in industrialized nations. However, there are still specific groups with high prevalence that might benefit from screening for early detection and treatment.


Effects of Bay k 8644 on the coronary vascular selectivity of the dihydropyridine Ca antagonists in the canine isolated, blood-perfused papillary muscle preparation.
Antagonism by Bay k 8644 of the coronary vasodilator and negative inotropic effects of Ca antagonists was simultaneously investigated in the canine isolated, blood-perfused papillary muscle electrically driven at 2 Hz. Drugs were given intraarterially. Continuously infused intraarterially, Bay k 8644 inhibited more predominantly the coronary vasodilator effects of the dihydropyridine Ca antagonists (nifedipine, nitrendipine, and nicardipine) than those of diltiazem and verapamil, or the negative inotropic effects of nifedipine and nitrendipine. The negative inotropic effects of nicardipine, diltiazem, and verapamil were not significantly affected by Bay k 8644. The dose ratio for producing a 50% decrease in developed tension of the papillary muscle over the dose for producing a 50% increase in coronary blood flow (which reflects vascular selectivity) were 41 for nitrendipine, 25 for nifedipine, 21 for nicardipine, 9 for diltiazem, and 7 for verapamil. During infusion by Bay k 8644, the ratio was small (2 to 6) and almost similar among all five Ca antagonists. These results indicate that Bay k 8644 antagonizes more effectively the coronary vasodilating effects of the dihydropyridine Ca antagonists, suggesting that there is a specific type of Ca channel on coronary vascular smooth muscles, through which the dihydropyridine Ca antagonists act.


[The role of cardioxane (ICRF-187) in the prevention of cardiotoxicity of anthracyclines in the combined drug therapy of extensive ovarian cancer].
The investigation was concerned with clinical application of cardioxane (dexrazoxan, ICRF-187) which is intended to counteract the cardiotoxic effect of anthracycline drugs. It was tested in 24 courses of combination chemotherapy (CAP) in 48 cases of extended ovarian tumor. The "threshold" total dose of doxorubin (500 mg/m2) which caused persistent cardiomyopathy in such patients as well as cases of relapse was practically never reached due to the absence of therapeutic effect. The total dose of doxorubicin of 120 mg/m2 raised the likelihood of acute cardiac intoxication. With prophylactic administration of cardioxane, clinical signs of acute cardiointoxication were slight; irreversible intoxication was recorded in 0.8%. The drug improved tolerance; it neither increased the overall toxicity of combination chemotherapy nor affected the results.


Molecular and clinical findings and their correlations in Silver-Russell syndrome: implications for a positive role of IGF2 in growth determination and differential imprinting regulation of the IGF2-H19 domain in bodies and placentas.
Silver-Russell syndrome (SRS) is characterized by growth failure and dysmorphic features and is frequently caused by hypomethylation (epimutation) of the H19-DMR. Although molecular and clinical studies have extensively been performed for SRS patients themselves, such studies have not been carried out for placentas. We identified 20 epimutation-positive and 40 epimutation-negative Japanese SRS patients and obtained placental weight data from 12 epimutation-positive and ten epimutation-negative patients and paraffin-embedded placental tissues for molecular and histological examinations from three epimutation-positive and two epimutation-negative patients. Methylation patterns were comparable between leukocytes and placentas in both epimutation-positive and epimutation-negative patients. Epimutations resulted in virtually no IGF2 expression and biallelic slight H19 expression in the leukocytes and obviously reduced IGF2 expression of paternal origin and nearly normal H19 expression of maternal origin in the placentas. Epimutation-positive patients had characteristic body phenotype and small placentas with hypoplastic chorionic villi, and epimutation-negative patients had somewhat small placentas with hypoplastic chorionic villi or massive infarction. Furthermore, significant correlations were identified between the H19-DMR methylation index and the body and placental sizes and between the placental weight and the body size in the epimutation-positive patients, whereas such correlations were not detected for the head circumference. These results suggest (1) characteristic phenotype and reduced IGF2 expression in the epimutation-positive placentas; (2) similarities and differences in the epigenetic control of the IGF2-H19 domain between leukocytes and placentas; (3) a positive role of the IGF2 expression level, as reflected by the methylation index, in the determination of body and placental growth in epimutation-positive patients, except for the brain where IGF2 is expressed biallelically; (4) involvement of placental dysfunction in prenatal growth failure; and (5) relevance of both (epi)genetic factor(s) and environmental factor(s) to SRS in epimutation-negative patients.


(5S)-3-oxo-4-oxa-endo-tricyclo[18.104.22.168(2,6)]dec-8-en-5-yl acetate.
The molecular structure of C(11)H(12)O(4), based on a norbornene core, was established to confirm the configuration of an acetoxy side-chain group in addition to the formation of the endo product. The acetoxy side chain lies in an axial position relative to the five-membered fused ring. Bond distances and angles show no unusual features, with all geometric parameters lying within their expected ranges. The overall stereochemistry of the molecule was ascertained from the chiral furanone starting material.


Broadening discussions of "safe" in hepatitis C prevention: a close-up of swabbing in an analysis of video recordings of injecting practice.
Blood awareness messages have been used for some years in hepatitis C prevention efforts. However, hepatitis C prevention education has achieved only limited success. Innovative means of reaching people who inject drugs (PWIDs) are required. This study involved video recording injecting episodes of 13 clients of the Sydney Medically Supervised Injecting Centre in Kings Cross. Participants were interviewed the following day and asked to review their video and comment on their injecting practice. Also, feedback was provided to the participants on injecting technique and hepatitis C prevention. A peer researcher was present and engaged the participant in discussion around safer practice and explored the participants' explanations of their practice. This analysis provides information about the common aspects of "safer" and "unsafer" injecting technique observed in the video recordings. Unsafer in this context was defined as any practice which could cause harm including blood borne virus transmission risks, vein damage and introduction of other pathogens to the blood stream. Analysis of the video data show that common "unsafer" practices which have implications for blood borne virus transmission include: not washing hands before injecting; using fingers to stop bleeding; wiping injection site with swab (instead of applying pressure) to stop bleeding after injecting; and using the same swab to wipe another site. Analysis of interview data provided participants' explanations of their practices. Analysis of the discussions between the interview team and the participant provides insight into the types of messages and communication strategies which had credibility with the participants. These data show that broadening of hepatitis C education discussions to include other aspects of "safer" injecting can be useful in engaging experienced PWIDs in prevention. Embedding blood borne virus prevention messages in discussions about vein care may provide innovative ways to reinvigorate hepatitis C prevention efforts and impart these messages in a context which acknowledges the skills and knowledge of experienced PWIDs.


Molecular analysis of TSC1 and TSC2 genes and phenotypic correlations in Brazilian families with tuberous sclerosis.
Tuberous sclerosis complex (TSC) is an autosomal dominant multisystem disorder characterized by the development of multiple hamartomas in many organs and tissues. It occurs due to inactivating mutations in either of the two genes, TSC1 and TSC2, following a second hit in a tumor suppressor gene in most hamartomas. Comprehensive screening for mutations in both the TSC1 and TSC2 loci has been performed in several cohorts of patients and a broad spectrum of pathogenic mutations have been described. In Brazil, there is no data regarding incidence and prevalence of tuberous sclerosis and mutations in TSC1 and TSC2. We analyzed both genes in 53 patients with high suspicion of tuberous sclerosis using multiplex-ligation dependent probe amplification and a customized next generation sequencing panel. Confirmation of all variants was done by the Sanger method. We identified 50 distinct variants in 47 (89%) of the patients. Five were large rearrangements and 45 were point mutations. The symptoms presented by our series of patients were not different between male and female individuals, except for the more common occurrence of shagreen patch in women (p = 0.028). In our series, consistent with other studies, TSC2 mutations were associated with a more severe phenotypic spectrum than TSC1 mutations. This is the first study that sought to characterize the molecular spectrum of Brazilian individuals with tuberous sclerosis.


Nickel(II)- and cobalt(II)-dependent damage by hydrogen peroxide to the DNA bases in isolated human chromatin.
Nickel compounds are known to be carcinogenic to humans and animals. Cobalt compounds produce tumors in animals and are probably carcinogenic to humans. The mechanisms of the carcinogenicity of these metal compounds, however, have remained elusive. In the present work, we have investigated the ability of Ni(II) and Co(II) ions in the presence of H2O2 to cause chemical changes in DNA bases in chromatin extracted from cultured cells of human origin. Eleven modified DNA bases in chromatin were identified and quantitated by the use of gas chromatography-mass spectrometry. 2-Hydroxyadenine (isoguanine), which has not previously been shown to occur DNA or chromatin, was also identified. Products identified were typical hydroxyl radical-induced products of DNA bases, suggesting that the hydroxyl radical was involved in their formation. This idea was supported by partial inhibition of product formation by typical scavengers of hydroxyl radical. Partial inhibition of product formation indicated a possible "site-specific" formation of hydroxyl radical by unchelated Ni(II) and Co(II) ions bound to chromatin. Although treatment of chromatin for 1 h with Co(II)/H2O2 caused formation of significant amounts of products, treatment with Ni(II)/H2O2 required incubation times of more than 5 h and an increase in Ni(II) concentration before increases in product amounts above background levels became detectable. In both cases, ascorbic acid did not increase product yields. Glutathione at a physiologically relevant concentration had little overall effect on DNA base modification. Superoxide dismutase increased the yields of most products. Chelation of Ni(II) and Co(II) ions with EDTA almost completely inhibited product formation. Ni(II) in the presence of H2O2 produced greater base damage to the DNA in chromatin than to isolated DNA, unlike other metal ions tested. DNA damage in chromatin caused by Ni(II) and Co(II) ions in the presence of H2O2 may contribute to the established genotoxicity and carcinogenicity of these metal ions.


Extraction of mRNA from soil.
Here, we report an efficient method for extracting high-quality mRNA from soil. Key steps in the isolation of total RNA were low-pH extraction (pH 5.0) and Q-Sepharose chromatography. The removal efficiency of humic acids was 94 to 98% for all soils tested. To enrich mRNA, subtractive hybridization of rRNA was most efficient. Subtractive hybridization may be followed by exonuclease treatment if the focus is on the analysis of unprocessed mRNA. The total extraction method can be completed within 8 h, resulting in enriched mRNA ranging from 200 bp to 4 kb in size.


Expression level of the mitotic checkpoint protein and G2-M cell cycle regulators and prognosis in gastrointestinal stromal tumors in the stomach.
The biological behavior of gastrointestinal stromal tumors (GISTs) ranges from benign to malignant, and the risk of an adverse outcome is correlated with the location of the primary tumor, tumor size, and mitotic counts. Cell cycle regulators are potentially associated with the tumorigenesis and progression of GISTs. Checkpoint with forkhead and ring finger (CHFR) functions as an important checkpoint protein in the early to mid-prophase to regulate mitosis. In this study, we evaluated the expression of CHFR and several cell cycle regulators, including cyclin A, cyclin B1, cdc2, and cdk2, by immunohistochemical staining in 53 cases of primary gastric GISTs, and compared the immunohistochemical results with the clinicopathological factors or the GIST risk grades as modified by Miettinen et al. Of the 53 cases, 18 (34%) showed decreased nuclear CHFR expression. Decreased CHFR expression was correlated with higher mitotic counts [>5/50 high-power fields (HPFs)] (p = 0.039) and a high-risk grade (p = 0.0475), but not with expression of other cell cycle regulators. Higher cyclin A labeling index (LI, >1.5%), cyclin B1 LI (>0.25%), cdc2 LI (>1.16%), Ki-67 LI (>4.9%), mitotic counts (>5/50 HPF) and high-risk grade were each associated with shorter disease-free survival (p = 0.0017, p = 0.003, p = 0.0471, p = 0.002, p < 0.001, and p = 0.0017, respectively). Our results suggest that modified risk grade and increased expression of G2-M regulators such as cyclin A, cyclin B1, and cdc2 are useful for predicting the biological behavior of gastric GISTs. In addition, decreased CHFR expression may play a role in increased proliferative activity of higher grade GISTs.


Repeated propofol anesthesia for a patient with a history of neuroleptic malignant syndrome.
Neuroleptic malignant syndrome (NMS) is the most serious side effect produced by the administration of antipsychotic drugs. NMS shares many clinical similarities with malignant hyperthermia (MH), but the etiology of NMS and the relation between NMS and MH remain unknown. Anesthetic regimens for patients with NMS are not well established. We gave repeated anesthesia to a patient with a history of NMS undergoing electroconvulsive therapy for the treatment of depression. Propofol and vecuronium were used in twelve consecutive ECT sessions without complications. In this case report, we describe the safe and satisfactory repeated use of propofol in a patient with a history of NMS, and outline NMS and its questionable relation to MH.


Angiotensin II type 1 receptor-mediated inflammation is required for choroidal neovascularization.
Choroidal neovascularization (CNV) is a critical pathogenesis in age-related macular degeneration, the most common cause of blindness in the developed countries. The aim of the current study was to determine the involvement of the renin-angiotensin system (RAS) with the development of CNV, using human surgical samples and the murine model of laser-induced CNV. In the human and murine CNV tissues, the vascular endothelium expressed angiotensin II type 1 receptor (AT1-R), AT2-R, and angiotensin II. The CNV volume was significantly suppressed by treatment with an AT1-R blocker telmisartan, but not with an AT2-R blocker. AT1-R signaling blockade with telmisartan inhibited various inflammatory mechanisms including macrophage infiltration and upregulation of VEGF, intercellular adhesion molecule-1 (ICAM-1), MCP-1, and IL-6 in the retinal pigment epithelium-choroid complex. A PPAR-gamma antagonist partially but significantly reversed the suppressive effect of telmisartan on in vivo induction of CNV and in vitro upregulation of ICAM-1 and MCP-1 in endothelial cells and IL-6 in macrophages, showing the dual contribution of PPAR-gamma-agonistic and AT1-R-antagonistic actions in the telmisartan treatment. AT1-R-mediated inflammation plays a pivotal role in the development of CNV, indicating the possibility of AT1-R blockade as a novel therapeutic strategy to inhibit CNV.


Brain and spinal MR imaging findings in mucopolysaccharidoses: a review.
MPS represents a group of rare hereditary disorders characterized by multisystem involvement due to intralysosomal GAG accumulation. Among various tissues, both the central and peripheral nervous system are affected in almost all types of the disease. Thus, brain and spinal MR imaging are valuable tools for the assessment of neurologic involvement, and there is evidence that they might be reliable markers demonstrating disease severity and efficacy of treatment options currently used in patients with MPS. We aimed to review the most prominent MR imaging features of patients with MPS, paying attention to the physiopathologic mechanisms responsible for these alterations. Along with the description of neuroimaging findings, existing data in relation to their correlation with the severity of neurologic involvement is discussed, while another topic of great importance is the effect of various therapeutic regimens in the progression of brain and spinal MR imaging alterations. Finally, recent data concerning MR spectroscopy studies in MPS are also critically discussed.


Clinical presentation and imaging of bone and soft-tissue sarcomas.
The clinical presentation of bone and soft-tissue sarcomas is varied. Constitutional symptoms are rare, and although bone sarcomas tend to be painful while soft-tissue sarcomas usually are not, there are exceptions to this general rule. A high index of suspicion is required for any unexplained mass with indeterminate imaging findings. Choosing the right imaging modality is critical to the diagnosis and management of patients with suspected sarcoma, and referring clinicians have a multitude of imaging options. After discovery of a malignant-appearing bone lesion by radiography, further imaging is obtained for better characterization of the lesion (typically with magnetic resonance imaging [MRI]) and for staging (typically with computed tomography of the chest). In contrast, radiographs are rarely helpful for evaluation of soft-tissue lesions, which almost always require MRI assessment.


Optimal patient education for cancer pain: a systematic review and theory-based meta-analysis.
Previous systematic reviews have found patient education to be moderately efficacious in decreasing the intensity of cancer pain, but variation in results warrants analysis aimed at identifying which strategies are optimal. A systematic review and meta-analysis was undertaken using a theory-based approach to classifying and comparing educational interventions for cancer pain. The reference lists of previous reviews and MEDLINE, PsycINFO, and CENTRAL were searched in May 2012. Studies had to be published in a peer-reviewed English language journal and compare the effect on cancer pain intensity of education with usual care. Meta-analyses used standardized effect sizes (ES) and a random effects model. Subgroup analyses compared intervention components categorized using the Michie et al. (Implement Sci 6:42, 2011) capability, opportunity, and motivation behavior (COM-B) model. Fifteen randomized controlled trials met the criteria. As expected, meta-analysis identified a small-moderate ES favoring education versus usual care (ES, 0.27 [-0.47, -0.07]; P = 0.007) with substantial heterogeneity (I² = 71 %). Subgroup analyses based on the taxonomy found that interventions using "enablement" were efficacious (ES, 0.35 [-0.63, -0.08]; P = 0.01), whereas those lacking this component were not (ES, 0.18 [-0.46, 0.10]; P = 0.20). However, the subgroup effect was nonsignificant (P = 0.39), and heterogeneity was not reduced. Factoring in the variable of individualized versus non-individualized influenced neither efficacy nor heterogeneity. The current meta-analysis follows a trend in using theory to understand the mechanisms of complex interventions. We suggest that future efforts focus on interventions that target patient self-efficacy. Authors are encouraged to report comprehensive details of interventions and methods to inform synthesis, replication, and refinement.


Differential effect of alpha-difluoromethylornithine on the in vivo uptake of 14C-labeled polyamines and methylglyoxal bis(guanylhydrazone) by a rat prostate-derived tumor.
The uptake of exogenously administered radiolabeled polyamines by a rat prostate-derived tumor line, the Dunning R3327 MAT-Lu, and various normal tissues was studied. Pretreatment of tumor cells in vitro with alpha-difluoromethylornithine (DFMO), a polyamine synthesis inhibitor, resulted in a markedly enhanced uptake of both [14C]putrescine and [14 C]spermidine. The in vitro uptake of [14C]putrescine by these cells was effectively inhibited by unlabeled spermine, spermidine, 1,8-diaminooctane, 1,7-diaminoheptane, 1,6-diaminohexane, 1,5-diaminopentane, 1,4-diaminopentane, and 1,4-diaminobutane, but less effectively by 1,4-diamino-2,3-butene and 1,4-diamino-2,3-butyne. The diamines, 1,3-diaminopropane and 1,2-diaminoethane, were ineffective in inhibiting [14C]putrescine uptake in vitro into the R3327 MAT-Lu cell line. When tumor-bearing animals were pretreated with DFMO or with DFMO and 5-alpha-dihydrotestosterone propionate, the tumor and prostate uptake of [14C]putrescine and [14C]-cadaverine was enhanced but not substantially increased in other tissues. In contrast to the in vitro results, spermidine and spermine were not enhanced substantially by DFMO pretreatment into any tissue, and their uptake into the tumor actually decreased. Ethylenediamine, which does not utilize the polyamine transport system, did not have its uptake increased into any tissue following DFMO pretreatment. The chemotherapeutic agent, methylglyoxal bis(guanylhydrazone), which utilizes the polyamine transport system for uptake into cells, exhibited uptake behavior different from that of the polyamines. Thus, methylglyoxal bis(guanylhydrazone) uptake into the tumor was not significantly increased or decreased by DFMO or by DFMO + 5-alpha-dihydrotestosterone propionate pretreatment, and only the ventral, but not the dorsal-lateral, lobe of the prostate showed increased uptake of methylglyoxal bis(guanylhydrazone) following DFMO + 5-alpha-dihydrotestosterone propionate pretreatment.


Perivascular human endometrial mesenchymal stem cells express pathways relevant to self-renewal, lineage specification, and functional phenotype.
Human endometrium regenerates on a cyclic basis from candidate stem/progenitors whose genetic programs are yet to be determined. A subpopulation of endometrial stromal cells, displaying key properties of mesenchymal stem cells (MSCs), has been characterized. The endometrial MSC (eMSC) is likely the precursor of the endometrial stromal fibroblast. The goal of this study was to determine the transcriptome and signaling pathways in the eMSC to understand its functional phenotype. Endometrial stromal cells from oocyte donors (n = 20) and patients undergoing benign gynecologic surgery (n = 7) were fluorescence-activated cell sorted into MCAM (CD146)(+)/PDGFRB(+) (eMSC), MCAM (CD146)(-)/PDGFRB(+) (fibroblast), and MCAM (CD146)(+)/PDGFRB(-) (endothelial) populations. The eMSC population contained clonogenic cells with a mesenchymal phenotype differentiating into adipocytes when cultured in adipogenic medium. Gene expression profiling using Affymetrix Human Gene 1.0 ST arrays revealed 762 and 1518 significantly differentially expressed genes in eMSCs vs. stromal fibroblasts and eMSCs vs. endothelial cells, respectively. By principal component and hierarchical clustering analyses, eMSCs clustered with fibroblasts and distinctly from endothelial cells. Endometrial MSCs expressed pericyte markers and were localized by immunofluorescence to the perivascular space of endometrial small vessels. Endometrial MSCs also expressed genes involved in angiogenesis/vasculogenesis, steroid hormone/hypoxia responses, inflammation, immunomodulation, cell communication, and proteolysis/inhibition, and exhibited increased Notch, TGFB, IGF, Hedgehog, and G-protein-coupled receptor signaling pathways, characteristic of adult tissue MSC self-renewal and multipotency. Overall, the data support the eMSC as a clonogenic, multipotent pericyte that displays pathways of self-renewal and lineage specification, the potential to respond to conditions during endometrial desquamation and regeneration, and a genetic program predictive of its differentiated lineage, the stromal fibroblast.


[Epidemiologic versions in investigation of Legionnaires' disease outbreak in town Verkhnyaya Pyshma].
Materials of investigation of Legionnaires' disease outbreak in one of the town of Sverdlovsk region in summer 2007 are presented. Outbreak arose in situation of epidemiologic welfare on majority of registered infectious diseases. Epidemiologic diagnostics of the outbreak has been performed in maximal shorttime interval, during which it was necessary to investigate variety of miscellaneous versions. Active search of the source of the infection and its transmission factors resulted in desired result and allowed to terminate the outbreak in 14 days.


Surgical therapy for dystonia.
Surgical treatments for dystonia have been available since the early 20th century, but have improved in their efficacy to adversity ratio through a combination of technologic advances and better understanding of the role of the basal ganglia in dystonia. The word "dystonia" describes a phenotype of involuntary movement that may manifest from a variety of conditions. Dystonia may affect only certain regions of the body or may be generalized. It appears to be critical to determine whether the etiology underlying the dystonia is "primary" (ie, occurring from a genetic or idiopathic origin) or "secondary" (ie, occurring as a result of structural, metabolic, or neurodegenerative disorders). Secondary dystonias are far more common than primary dystonias. Primary dystonias respond well to pallidotomy or deep brain stimulation of the internal segment of the globus pallidum, whereas secondary dystonias appear to respond partially at best. Limited historic and current data suggest that the thalamus may be a promising target for the treatment of secondary dystonias, but more careful, prospective, randomized studies are needed. Combinations of bilateral targets are possible with the current technology of DBS, but not widely used due to surgical morbidity and expense. This article reviews the surgical treatment of dystonia from past to present, with a focus on separating the outcomes for primary versus secondary and generalized versus cervical dystonia.


The effects of scapular mobilization in patients with subacromial impingement syndrome: a randomized, double-blind, placebo-controlled clinical trial.
To determine the effects of scapular mobilization on function, pain, range of motion, and satisfaction in patients with subacromial impingement syndrome (SAIS). Randomized, double-blind, placebo-controlled clinical trial. University hospital clinics in Turkey. 66 participants (mean ± SD age 52.06 ± 3.71 y) with SAIS. Participants were randomized into 3 groups: scapular mobilization, sham scapular mobilization, and supervised exercise. Before the interventions transcutaneous electrical stimulation and hot pack were applied to all groups. Total intervention duration for all groups was 3 wk with a total of 9 treatment sessions. Shoulder function and pain intensity were primary outcome measures; range of motion and participant satisfaction were secondary outcome measures. Shoulder function was assessed with the short form of the Disabilities of the Arm, Shoulder and Hand Questionnaire (DASH). A visual analog scale was used to evaluate pain severity. Active range of motion was measured with a universal goniometer. A 7-point Likert scale was used to evaluate satisfaction. Outcome measurements were performed at baseline, before visits 5 and 10, 4 wk after visit 9, and 8 wk after visit 9. There was no group difference for DASH score (P = .75), pain at rest (P = .41), pain with activity (P = .45), pain at night (P = .74), and shoulder flexion (P = .65), external rotation (P = .63), and internal rotation (P = .19). There was a significant increase in shoulder motion and function and a significant decrease in pain across time when all groups were combined (P < .001). The level of satisfaction was not significantly different for any of the questions about participant satisfaction between all groups (P > .05). There was not a significant advantage of scapular mobilization for shoulder function, pain, range of motion, and satisfaction compared with sham or supervised-exercise groups in patients with SAIS.


Long-term results of a pilot study for the treatment of advanced unresectable head and neck tumors by combination chemotherapy and split course radiotherapy.
The results of treatment of 30 patients with advanced unresectable squamous cell carcinoma of the head and neck (stage III and IV) are presented. These patients were treated in a pilot study using kinetically based combination chemotherapy and split course radiotherapy from July 1977 until December 1979. Twenty-three patients (76%) achieved a local response (53% complete and 23% partial) and the median survival was 16 months. The two-year survival was 43%. Although no significant increase in acute radiation morbidity was seen, 43% of the patients developed chronic symptomatic complications. Seven patients (23%) developed second primary cancers, of which five were bronchogenic carcinomas and two were esophageal carcinomas. The regimen adopted produced a high local control rate with permanent local control in 50% of patients treated, but this was achieved at the expense of a high chronic toxicity rate. The incidence of second primary malignancies, presumably because of on-going environmental factors, remains a continuing concern.


Serum levels of vitamins A, C, and E, beta-carotene, selenium, and zinc in patients with Behçet's disease: a controlled study.
Behçet's disease is a multisystemic disease characterized by activation and remission periods. The etiopathogenesis is not exactly known; a genetic defect in the immunoregulatory system induced by infectious agents, like viruses and bacteria, is thought to cause the disease. In this study, we examine the serum levels of vitamins A, C, and E, beta-carotene, selenium, and zinc in Behçet's disease patients and investigate the relationship between these serum levels and the activation of the disease. We conclude that adding vitamin E to the treatment of Behçet's disease patients and its effects on the prognosis of the disease need to be further investigated by controlled studies.


Streptococcus anginosus-constellatus infections of the nervous system.
Two patients are presented with central nervous system infections due to an uncommon type of viridans streptococci, S anginosus-constellatus. Of the various streptococci, S pneumoniae is the most common etiologic agent in meningitis, but many species, including those which are facultative anaerobes or microaerophiles, have been isolated from cerebrospinal fluid, subdural empyema, and abscesses involving the brain and epidural space.


Synthesis, characterization and potential applications of multifunctional PEO-PPOPEO- magnetic drug delivery system.
Magnetic nanocomposites (MNCs) have highly been acknowledged in the diagnostics and therapeutic applications. Particularly, the multifunctional MNCs have brought a variety of possibilities in targeted drug delivery as well as non-invasive multimodality imaging. A temperature-responsive magnetic drug delivery system has been developed which is made up of superparamagnetic iron oxide nanoparticles (SIONPs) core and Pluronic shell. The magnetic cores composed of congo red conjugated to SIONPs have been proved beneficial as multimodal imaging agents, while superparamagnetic properties facile conducting the nano or micro systems to the vicinity of targeted tissue. Polymer shell formed by stimuli-responsive Pluronic F127 poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) PEO-PPO-PEO block copolymer serves as the carrier for both hydrophilic and hydrophobic drugs. X-ray diffraction (XRD) and high-resolution transmission electron microscope (HR-TEM) were used to characterize as-synthesized MNCs. Furthermore, vibrating magnetometer experiments showed MNCs having a higher magnetization value than bare magnetic nanoparticles (MNPs) and easy to conduct with an external magnetic field. The hydrodynamic size of MNCs was found to be varying in response to the stimuli temperature. Once the temperature increased, the hydrodynamic radius of MNCs decreased. In addition, the feasibility of the system as a targeted drug delivery system for Alzheimer's diseases (AD) diagnosis and therapy was studied. Searching for reliable targeting molecule, recent approaches for identification of amyloid-β (Aβ) and its derivatives have been evaluated. Consequently, the amyloid-derived diffusible ligands antibodies (anti-ADDLs) have been nominated as potential targeting molecules which can be attached to the MNCs system. The possibility of anti-ADDLs conjugation to DDS has been found promising for the multifunctional drug delivery system for AD diagnosis and therapy. However, further experimental studies are required to assess the performance of the proposed DDS.


Adhesion of L1210 cells to modified styrene copolymer surfaces in the presence of serum.
The static adhesion of living L1210 cells (in serum-containing medium) to the surface of (styrene/methylmethacrylate) copolymers differing in styrene content (from 5% to 50% of styrene units) was investigated. The examination of wettability of the copolymer surfaces showed that the contact angle of water on the hydrophobic surfaces is an increasing linear function of styrene content in the copolymer. Cell adhesion to the unwettable surfaces is low (within 2-4%). A novel method of modification of the styrene copolymer surfaces was used to render these surfaces suitable for cell attachment. The modification consists of sulfonation of the surfaces with sulfur trioxide at the gas/solid interface. The contact angle of sulfonated copolymer surfaces is a decreasing linear function of styrene content in the copolymer. The contact angle decreases due to the increased number of highly hydrophilic sulfonic groups bonded to styrene. By acetylation of the sulfonated surfaces it was shown that cell adhesion to acetylated surfaces is not diminished and is at the same level as cell adhesion to sulfonated copolymer surfaces. Thus, it can be concluded that sulfonation of copolymer surfaces does not form hydroxyl groups. Cell adhesion to substrata of high wettability stabilizes after 30s. The relative number of cells adhering to the sulfonated copolymer surfaces is a decreasing linear function of the contact angle. For the copolymer surfaces containing 50% of styrene units the contact angle decreases sevenfold, due to sulfonation, and the number of adhering cells increases 40-fold. The results obtained show that for cell-substratum adhesive interaction the presence of sulfonic groups at the substratum surface is important.


Masked priming and ERPs dissociate maturation of orthographic and semantic components of visual word recognition in children.
This study examined the time-course of reading single words in children and adults using masked repetition priming and the recording of event-related potentials. The N250 and N400 repetition priming effects were used to characterize form- and meaning-level processing, respectively. Children had larger amplitude N250 effects than adults for both shorter and longer duration primes. Children did not differ from adults on the N400 effect. The difference on the N250 suggests that automaticity for form processing is still maturing in children relative to adults, while the lack of differentiation on the N400 effect suggests that meaning processing is relatively mature by late childhood. The overall similarity in the children's repetition priming effects to adults' effects is in line with theories of reading acquisition, according to which children rapidly transition to an orthographic strategy for fast access to semantic information from print.