MicroRNA-206 prevents the pathogenesis of hepatocellular carcinoma by modulating expression of met proto-oncogene and cyclin-dependent kinase 6 in mice.
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide, and therapeutic agents for this malignancy are lacking. MicroRNAs play critical roles in carcinogenesis and present tremendous therapeutic potential. Here, we report that microRNA-206 is a robust tumor suppressor that plays important roles in the development of HCC by regulating cell-cycle progression and the cMet signaling pathway. MicroRNA-206 was underexpressed in livers of two HCC mouse models, human individuals bearing HCC, and human HCC cell lines. Combining bioinformatic prediction and molecular and cellular approaches, we identified cMET (Met proto-oncogene), cyclin D1 (CCND1), and cyclin-dependent kinase 6 (CDK6) as functional targets of microRNA-206. By inhibiting expression of cMET, CCND1, and CDK6, microRNA-206 delayed cell-cycle progression, induced apoptosis, and impaired proliferation of three distinct human HCC cell lines. Systemic administration of microRNA-206 completely prevented HCC development in both cMyc and V-Akt murine thymoma viral oncogene homolog 1/neuroblastoma RAS viral oncogene homolog (AKT/Ras) HCC mice, whereas 100% of control mice died from lethal tumor burdens. Conversely, reintroduction of cMet or Cdk6 into livers of cMyc and AKT/Ras HCC mice recovered growth of HCC inhibited by microRNA-206. These results strongly suggested that cMet and Cdk6 were two functional targets that mediated the inhibitory effect of microRNA-206 on the development of HCC. MicroRNA-206 overexpression demonstrated a profound therapeutic effect on HCC in xenograft and cMyc HCC mice. In summary, this study defines a potentially critical role of microRNA-206 in preventing the growth of HCC and suggests its use as a potential therapeutic strategy for this malignancy. (Hepatology 2017;66:1952-1967).


Jung's mediatory science as a psychology beyond objectivism.
In this paper, the author argues that Jung's non-objectivist--yet scientific--epistemology and his empirical/hermeneatic methods of inquiry situate him within a psychological tradition that, in many respects, began with William James and, today, is finding expression in the work of many non-Jungian cognitive scientists. In an effort to encourage dialogue between Jungians and scholars within related intellectual traditions, the author presents evidence from the corpus of Jung's work that demonstrates that, like William James, Jung intentionally rejected the absolutist claims of objectivism and the opposite position on 'anything goes' relativism, emotivism, or subjectivism. Instead, Jung forged a path that led to the meta-psychological position similar to internal realism (Putnam 1981) or experientialism (Lakoff 1987) and to a theoretical psychology that gave a central place both to unconscious cognitive structure and to imagination. This he labelled a 'mediatory science'. The psychological theories developed within this mediatory science framework represent an early articulation of key constructs that are currently used by a number of cognitive scientists seeking to understand how we make sense of experience.


Whole body cryotherapy, cold water immersion, or a placebo following resistance exercise: a case of mind over matter?
The use of cryotherapy as a recovery intervention is prevalent amongst athletes. Performance of high volume, heavy load resistance exercise is known to result in disturbances of muscle function, perceptual responses and blood borne parameters. Therefore, this study investigated the influence of cold water immersion (CWI), whole body cryotherapy (WBC) or a placebo (PL) intervention on markers of recovery following an acute resistance training session. 24 resistance trained males were matched into a CWI (10 min at 10 °C), WBC (3- and 4 min at - 85 °C) or PL group before completing a lower body resistance training session. Perceptions of soreness and training stress, markers of muscle function, inflammation and efflux of intracellular proteins were assessed before, and up to 72 h post exercise. The training session resulted in increased soreness, disturbances of muscle function, and increased inflammation and efflux of intracellular proteins. Although WBC attenuated soreness at 24 h, and positively influenced peak force at 48 h compared to CWI and PL, many of the remaining outcomes were trivial, unclear or favoured the PL condition. With the exception of CRP at 24 h, neither cryotherapy intervention attenuated the inflammatory response compared to PL. There was some evidence to suggest that WBC is more effective than CWI at attenuating select perceptual and functional responses following resistance training. However, neither cryotherapy intervention was more effective than the placebo treatment at accelerating recovery. The implications of these findings should be carefully considered by individuals employing cryotherapy as a recovery strategy following heavy load resistance training.


Geographic measures of retail food outlets and perceived availability of healthy foods in neighbourhoods.
To examine associations between geographic measures of retail food outlets and perceived availability of healthy foods. Cross-sectional. A predominantly rural, eight-county region of South Carolina, USA. Data from 705 household shoppers were analysed using ordinary least-squares regression to examine relationships between geographic measures (presence and distance) of food outlets obtained via a geographic information system and perceived availability of healthy foods (fresh fruits and vegetables and low-fat foods). The presence of a supermarket within an 8·05 km (5-mile) buffer area was significantly associated with perceived availability of healthy foods (β=1·09, P=0·025) when controlling for all other food outlet types. However, no other derived geographic presence measures were significant predictors of perceived availability of healthy foods. Distances to the nearest supermarket (β=-0·16, P=0·003), dollar and variety store (β=-0·15, P=0·005) and fast-food restaurant (β=0·11, P=0·015) were all significantly associated with perceptions of healthy food availability. Our results suggest that distance to food outlets is a significant predictor of healthy food perceptions, although presence is sensitive to boundary size. Our study contributes to the understanding and improvement of techniques that characterize individuals' food options in their community.


Study of Stroke Incidence in the Aseer Region, Southwestern Saudi Arabia.
Recent data regarding first-stroke incidence in Saudi Arabia in general and in the Aseer region in particular are scarce and even lacking. The aim of this work was to study the first-time stroke incidence in the Aseer region, southwestern Saudi Arabia. All first-stroke patients admitted to all hospitals in the Aseer region over a one-year period (January through December 2016) were included. Stroke patients outside the Aseer region were excluded from the study. The incidence per 100,000 patients and the concomitant 95% CI (Confidence Intervals) were computed. The present study included 1249 first-time stroke patients and calculated an overall minimal incidence rate of hospitalized first-time stroke of 57.64 per 100,000 persons per year (95% CI: 57.57-57.70). A steady increase was noticed depending on the patients' age, reaching a figure of 851.81 (95% CI: 849.2-854.5) for those patients aged 70 years and more. Overall, the incidence rate for females (48.14; 95% CI: 48.04-48.24) was lower compared to males (65.52; 95% CI: 65.1-66.0). Taking into consideration the expected rise of the elderly because of the prominent medical services provided by the Saudi government, leading to a subsequent change in the horizontal and vertical age distribution structure of the population, an increase in the number of stroke patients is expected. It is suggested to establish a nationwide stroke surveillance system in the Kingdom, with the objective to report, analyze, and maintain an updated overview of the stroke status in Saudi Arabia.


C-X-C motif chemokine receptor 4 promotes tumor angiogenesis in gastric cancer via activation of JAK2/STAT3.
C-X-C motif chemokine receptor 4 (CXCR4) overexpression promotes gastric cancer growth and metastasis. In this study, we determined its role in regulating tumor angiogenesis. We overexpressed CXCR4 in gastric cancer cells and examined the effects of conditioned medium on endothelial cell proliferation, migration, and tube formation. The effects of CXCR4 overexpression on vascular endothelial growth factor (VEGF) expression and signal transducer and activator of transcription 3 (STAT3) activation were analyzed. In vivo xenograft studies were done to confirm the role of CXCR4 in tumor angiogenesis. Conditioned medium from CXCR4-overexpressing gastric cancer cells stimulated endothelial cell proliferation, migration, and tube formation. Such effects were blocked by addition of a neutralizing anti-VEGF antibody. CXCR4 induced VEGF production and JAK2/STAT3 activation and enhanced STAT3 binding to VEGF promoter in gastric cancer cells. Delivery of a dominant negative variant of STAT3 significantly impaired CXCR4-induced upregulation of VEGF. Overexpression of CXCR4 facilitated tumor growth and angiogenesis in SGC7901 xenograft tumors, which was associated with increased levels of phospho-STAT3. CXCR4 contributes to tumor angiogenesis in gastric cancer by inducing STAT3-dependent VEGF expression and represents a promising therapeutic target for this malignancy.


Molecularly targeted treatment of chronic myeloid leukemia: beyond the imatinib era.
Chronic myeloid leukemia cells contain a BCR-ABL oncoprotein with an enhanced tyrosine kinase activity, which is considered to be the principal 'cause' of the leukemia. Though the precise mechanisms underlying the leukemogenesis remains enigmatic, the use of imatinib to inhibit the dysregulated kinase activity has proved remarkably successful in clinical practice. Imatinib was the first small molecule developed to inhibit BCR-ABL tyrosine kinase activity and its success introduced the current era of molecularly targeted therapies for a number of other malignancies. In patients with chronic myeloid leukaemia who develop resistance to imatinib, the Bcr-Abl signaling pathway is often re-established. This has led to the emergence of a number of alternative treatment strategies designed to target the leukemic cell which are resistant to imatinib.


Experiences of adolescents living with cancer: A descriptive qualitative study.
This study aimed to explore the experiences of adolescents from Singapore, aged 10-18 years old, living with cancer and their perceptions on how their psychosocial outcomes can be improved. A descriptive qualitative study design was used. Convenience sampling was used to recruit 10 participants from a pediatric oncology ward in a Singapore hospital. Individual semi-structured interviews were conducted. Thematic analysis was used to analyze the data. Five major themes emerged: (1) experience of physical symptoms, (2) emotional response to their condition, (3) changes in social dynamics, and (4) falling behind in academics. The psychosocial outcomes of Singaporean adolescents with cancer could be improved by thorough pain assessments and creating a more conducive hospital environment.


Transcriptional repressor GATA binding 1-mediated repression of SRY-box 2 expression suppresses cancer stem cell functions and tumor initiation.
Cancer stem cells (CSCs) have been reported in a variety of cancers. SRY-box 2 (SOX2) is a member of the SOX family of transcription factors and has been shown to play a critical role in maintaining the functions of CSCs and promoting tumor initiation. However, the underlying mechanisms for the transcriptional regulation of the SOX2 gene in CSCs are unclear. In this study, using in silico and experimental approaches, we identified transcriptional repressor GATA binding 1 (TRPS1), an atypical GATA-type transcription factor, as a critical transcriptional regulator that represses SOX2 expression and thereby suppresses cancer stemness and tumorigenesis. Mechanistically, TRPS1 repressed SOX2 expression by directly targeting the consensus GATA-binding element in the SOX2 promoter as elucidated by ChIP and luciferase reporter assays. Of note, in vitro mammosphere formation assays in culture and in vivo xenograft tumor initiation experiments in mouse models revealed that TRPS1-mediated repression of SOX2 expression suppresses CSC functions and tumor initiation. Taken together, our study provides detailed mechanistic insights into CSC functions and tumor initiation by the TRPS1-SOX2 axis.


Barley grain-based diet treated with lactic acid and heat modulated plasma metabolites and acute phase response in dairy cows.
This study investigated the effects of feeding barley grain treated with lactic acid (LA) and heat on the profile of plasma metabolites related to carbohydrate and lipid metabolism and variables related to rumen health and acute phase response. Eight primiparous rumen-fistulated lactating Holstein cows were randomly assigned, in a crossover design, to 1 of the 2 dietary treatments consisting of 32% (DM basis) rolled barley grain steeped in an equal quantity of either tap water alone (CTR) or a 1.0% LA solution and heated at 55°C for 48 h (LAH). Each experimental period was 21 d, with the last 10 d used for measurements. Blood samples were collected on d 1, 3, 5, 7, 9, and 11 before the morning feeding and on the last day of each period at 0, 2, 4, 6, 8, 10, and 12 h postfeeding to measure glucose, lactate, cholesterol, beta-hydroxybutyrate (BHBA), NEFA, haptoglobin (Hp), serum amyloid A (SAA), and tumor necrosis factor-alpha (TNF-α). Also, rumen samples were collected on d 1, 5, and 11 as well as at 0, 4, 8, and 12 h postfeeding on the last day of each period for measuring the concentration of rumen endotoxin. Results of the day-to-day analysis indicated that cows fed the LAH diet had reduced preprandial concentrations of rumen endotoxin (472 vs. 793 ng/mL; P < 0.01) and cholesterol and greater lactate in the plasma; however, treatment had no effect on plasma Hp and TNF-α (P > 0.10). Postprandial responses showed that the LAH diet tended to decrease the concentration of SAA (4.67 vs. 8.50 μg/mL; P = 0.06). Also, there was a treatment by time interaction for rumen endotoxin (P < 0.01), suggesting a role for both the treatment and the time of sampling on this variable. Furthermore, greater concentration of BHBA and a tendency for greater NEFA and reduced concentrations of plasma glucose were observed in cows fed the LAH diet. In conclusion, results indicated that feeding dairy cows barley grain steeped in 1.0% LA and treated with heat modulated the profile of plasma metabolites and acute phase response.


Expanding the scope of bis(catecholato)germane catalysis: hydrosilylation, hydroboration, Friedel-Crafts alkylation and oligomerization.
Various applications of bis(catecholato)germanes in catalysis were examined. The hydrosilylation of benzaldehydes, hydroboration of phenylacetylene derivatives, and Friedel-Crafts alkylation using arylalkenes and either diphenylamine or anisole was achieved. Furthermore, the recently reported oligomerization of α-methylstyrene catalyzed by bis(catecholato)germanes with weak donor ligands was examined further. The formation of a trimer species was observed in DCM. VTNA and Hammett analyses of the oligomerization reaction were conducted and an updated mechanism for bis(catecholato)germane catalysis is proposed.


Effect of strain-induced anisotropy on magnetization dynamics in Y3Fe5O12 films recrystallized on a lattice-mismatched substrate.
We report on the correlation of structural and magnetic properties of Y3Fe5O12 (YIG) films deposited on Y3Al5O12 substrates using pulsed laser deposition. The recrystallization process leads to an unexpected formation of interfacial tensile strain and consequently strain-induced anisotropy contributing to the perpendicular magnetic anisotropy. The ferromagnetic resonance linewidth of YIG is significantly increased in comparison to a film on a lattice-matched Gd3Ga5O12 substrate. Notably, the linewidth dependency on frequency has a negative slope. The linewidth behavior is explained with the proposed anisotropy dispersion model.


Ring1A and Ring1B inhibit expression of Glis2 to maintain murine MOZ-TIF2 AML stem cells.
Eradication of chemotherapy-resistant leukemia stem cells is expected to improve treatment outcomes in patients with acute myelogenous leukemia (AML). In a mouse model of AML expressing the MOZ-TIF2 fusion, we found that Ring1A and Ring1B, components of Polycomb repressive complex 1, play crucial roles in maintaining AML stem cells. Deletion of Ring1A and Ring1B (Ring1A/B) from MOZ-TIF2 AML cells diminished self-renewal capacity and induced the expression of numerous genes, including Glis2 Overexpression of Glis2 caused MOZ-TIF2 AML cells to differentiate into mature cells, whereas Glis2 knockdown in Ring1A/B-deficient MOZ-TIF2 cells inhibited differentiation. Thus, Ring1A/B regulate and maintain AML stem cells in part by repressing Glis2 expression, which promotes their differentiation. These findings provide new insights into the mechanism of AML stem cell homeostasis and reveal novel targets for cancer stem cell therapy.


Combinational use of lipid-based reagents for efficient transfection of primary fibroblasts and hepatoblasts.
Commercially available lipid-based transfection reagents are widely used to deliver DNA to cells. However, these lipid-based transfection reagents show poor gene transfer efficiency in primary cells. Here, we demonstrate a simple method to improve gene transfer efficiency in primary fibroblasts and hepatoblasts using a combination of lipid-based transfection reagents. Our data show that combined use of Lipofectamine LTX and FuGENE HD increases the efficiency of gene transfer compared with the use of either reagent alone, and this combination achieves the best result of any pairwise combination of Lipofectamine LTX, FuGENE HD, TransFectin, and Fibroblast Transfection Reagent.


Predictors of treatment retention in a major methadone maintenance treatment program in iran: a survival analysis.
To identify correlates related to retention time of a cohort study of the opioid-dependent patients participating in the Methadone Maintenance Treatment (MMT) program offered by a major addiction treatment clinic in Tehran, Iran between April 2007 and March 2011. Several parametric Survival models assuming Weibull, Log-normal and Log-logistic distributions were compared to search for association between covariates and risk of relapse and dropping out of treatment among 198 patient participants. According to Akaike Information Criterion (AIC), Log-normal model had the best fitting. Estimates of this model indicated that increase in average methadone dosage was associated with longer retention time. Correlates associated with shorter retention time were suffering from mental disorders, using stimulant drugs, being poly-substance dependents and having prior treatments. Findings of this study provide support for giving more attention to patients who are poly-substance or stimulant-drug dependents, have non-substance psychiatric comorbidity and the ones with addiction treatment history. Independent of patient characteristics, retention improved as the dose of methadone increased.


Incidence of Ophthalmic Disorders in Patients Treated with the Antineoplastic Agent S-1.
S-1 is an oral antineoplastic agent containing tegafur, gimeracil, and oteracil potassium. Recently, ophthalmic disorders, particularly epiphora, have been reported. We retrospectively investigated the incidence of ophthalmic disorders in patients treated with a regimen containing S-1 at our institution. Ophthalmic disorders were noted in 28 of 261 patients(10.7%). These included epiphora(17 cases), eye discharge(10 cases), conjunctivitis(6cases ), blurred vision(3 cases), and eye discomfort(2 cases), as well as eye pain, pruritus, dry eye, hordeolum, and visual loss(1 case each). The median time from starting treatment to appearance of the condition was 3.0(interquartile range 1.5-4.5)months and the median cumulative S-1 dose was 4.2(interquartile range 2.2-9.5)g. More men than women developed ophthalmic disorders on S-1. The median total dose and duration of treatment were higher in those developed ophthalmic disorders than in those who did not (12.4 g vs 6.3g and 8.6 months vs 4.4 months). Epiphora was the most common of a number of ophthalmic disorders seen in our patients treated with S-1. Patients and physicians should be fully informed of the potential association between S-1 and ophthalmic disorders, and patients receiving this treatment need to be carefully monitored.


Oral administration of glucose promotes intracellular partitioning of fatty acid toward storage in white but not in red muscle.
Lipid accumulation in non-adipose tissues is strongly associated with the metabolic syndrome, possibly due to aberrant partitioning of intracellular fatty acids between storage and oxidation. In the present study, we administered the non-metabolizable fatty acid analog [9,10-(3)H]-(R)-2-bromopalmitate, and authentic (14)C-palmitate to conscious rats, in order to directly examine the initial intracellular fate of fatty acids in a range of insulin-sensitive tissues, including white and red muscles, liver, white adipose tissue, and heart. Rats were studied after administration of an oral glucose load to examine the effect of physiological elevation of glucose and insulin. The tracer results showed that glucose administration partitioned fatty acid toward storage in white muscle (storage:uptake ratios, vehicle vs glucose; 0.64 +/- 0.02 vs 0.92 +/- 0.09, P < 0.05), and in liver (0.66 +/- 0.07 vs 0.98 +/- 0.04, P < 0.05), but not in red muscle (1.18 +/- 0.07 vs 1.36 +/- 0.11, P = not significant). These results demonstrate the physiological relevance of the so-called 'reverse' Randle cycle, but surprisingly show that it may be more important in white rather than oxidative red muscle.


Familial chilblain lupus due to a novel mutation in the exonuclease III domain of 3' repair exonuclease 1 (TREX1).
Familial chilblain lupus is a rare, autosomal dominant form of lupus erythematosus characterized by cold-induced inflammatory lesions at acral locations presenting in early childhood. Familial chilblain lupus is usually caused by a mutation in TREX1 (3' repair exonuclease 1). We report on a family with dominant chilblain lupus segregating a novel TREX1 mutation (c.585C>G; H195Q) within the highly conserved exonuclease (Exo) III domain. Affected family members experienced cold-induced chilblain lesions of varying degrees, ranging from bluish-red infiltrations to mutilating necrotic ulcerations. In addition, all patients showed signs of systemic disease, such as arthritis, lymphopenia, or antinuclear antibodies. An increased expression of myxovirus resistance protein A in the skin and induction of interferon-stimulated genes in peripheral blood cells demonstrated activation of type I interferon. This case further implicates type I interferon-dependent innate immune activation in the pathogenesis of TREX1-associated familial chilblain lupus. Unlike previously reported TREX1 mutations, which affect the Exo I or Exo II domains, the mutation presented here alters the Exo III domain, suggesting a particular role of mutations within the catalytic Exo domains in the pathogenesis of familial chilblain lupus. The high prevalence of extracutaneous manifestations, along with activation of type I interferon, underlines the systemic nature of familial chilblain lupus.


Scalable boson sampling with time-bin encoding using a loop-based architecture.
We present an architecture for arbitrarily scalable boson sampling using two nested fiber loops. The architecture has fixed experimental complexity, irrespective of the size of the desired interferometer, whose scale is limited only by fiber and switch loss rates. The architecture employs time-bin encoding, whereby the incident photons form a pulse train, which enters the loops. Dynamically controlled loop coupling ratios allow the construction of the arbitrary linear optics interferometers required for boson sampling. The architecture employs only a single point of interference and may thus be easier to stabilize than other approaches. The scheme has polynomial complexity and could be realized using demonstrated present-day technologies.


[A case of acute appendicitis which occurred during chemotherapy for breast cancer].
The patient was a 66-year-old woman with left breast cancer who underwent left segmental mastectomy with sentinel lymph node biopsy. The histopathological diagnosis was estrogen receptor-positive (ER+), progesterone receptor-positive( PgR+), human epidermal growth factor receptor-2-equivocal( HER2()2+)( with no HER2 gene amplification by fluorescence in-situ hybridization analysis) invasive ductal carcinoma (scirrhous carcinoma) with Ki-67 expression of less than 10% (pathological T1c, N0, M0, stage I). The patient requested chemotherapy, and 4 cycles of docetaxel plus cyclophosphamide (TC) were scheduled. Fever and epigastric pain developed on day 13 of cycle 2. On day 22, the patient was examined before the third cycle of TC, and right lower abdominal pain was reported. Computed tomography revealed appendicitis and an intraperitoneal abscess. She was admitted to the hospital and underwent partial ileocecal resection. The patient was discharged on the 12th postoperative day with no further complications. Acute abdomen during chemotherapy for malignant tumors has been reported sporadically in patients with leukemia. A diagnosis of acute abdomen in patients undergoing cancer treatment requires careful assessment of gastrointestinal symptoms such as nausea and vomiting during chemotherapy, fever associated with granulocytopenia, and findings indicative of local inflammation. The patient in this case recovered uneventfully because imaging studies and surgery were performed promptly after presentation.


[Bases on timing of combined modality of chemotherapy and immunotherapy].
Chemoimmunotherapy with anticancer drugs and immunoregulatory drugs and cytokines is a logical combination of 2 forms of therapy that have different mechanisms of action and no overlapping toxicity. Generally, anticancer drugs show rapidly the strong suppressive effect on tumor growth but also on host hemato-immunological functions. On the other hand, immunotherapy demonstrate the potential of restoring the hemato-immunological dysfunction of chemotherapy as well as the gradual antitumor effect through activating host defense mechanisms against cancer, indicating that these therapeutic modalities are complementary. On these biological rationale of chemoimmunotherapy mentioned above, we have demonstrated that immunostimulant, Nocardia-CWS is capable of producing tumoricidal macrophages being different from anticancer drugs in cytotoxic mechanism against cancer, and also that macrophage tumoricidal activity is significantly suppressed by exposure to anticancer drug, mitomycin C. Another beneficial activity of immunostimulant showed in our previous studies is a capability of production of colony stimulating activities. In a cooperative study with lung cancer patients it has been shown that recovery of leucopenia after chemotherapy is accelerated by administration of immunostimulant, MDP-Lys. Recently, immunomodulatory lymphokine, IL-2, has been clinically used for induction of activated killer lymphocytes (LAK cells) with tumoricidal activity. According to our studies, however, anticancer drug, when administered to cancer patients or added directly to culture of lymphocytes with IL-2 for LAK induction, shows significant suppressive effect on LAK induction. Considering these experimental and clinical studies, it can be concluded that immunotherapy, when employed as adjuvant after chemotherapy, play the important roles not only in eradication of tumor cells being escaped from chemotherapy but also in prevention of infections complication by activating host defense mechanisms common to cancer and infection.


Descriptions of Two Digenean Trematodes Found from a Chinese Sea Snake, Laticauda semifasciata, in Republic of Korea.
We intended to describe 2 digenean trematodes found from a Chinese sea snake, Laticauda semifasciata, as the new fauna in the Republic of Korea. The snake was caught offshore of Aewol-eup, Jeju-do, in August 2017. Two species of fluke were found in the lung and intestinal tract of the snake in the process of necropsy. They were identified as Pulmovermis cyanovitellosus Coil and Kuntz, 1960 and Harmotrema laticaudae Yamaguti, 1933, respectively based on the morphological characters. Pulmovermis cyanovitellosus showed elongated body with well-developed and elongated male genital system and compact vitelline. And H. laticaudae was characterized by linguiform body with heavily armed cirrus with excretory system. This is the first time both species have been reported and described off the Korean coast. We provide morphological descriptions with some comments on their biology and geographical distribution. In addition, the taxonomic validity of the genus Hydrophitrema Sandars, 1960 was discussed, in terms of morphological descriptions and host ranges. This study provides novel insight into digenean fluke species existing off the coast of Korea.


Spontaneous dissection and rupture of common iliac artery in a patient with fibromuscular dysplasia: a case report and review of the literature on iliac artery dissections secondary to fibromuscular dysplasia.
Spontaneous dissection and rupture of the iliac artery is an unusual finding in patients with fibromuscular dysplasia (FMD). We report the case of a patient with FMD who required emergent surgery because of rupture of an iliac artery dissection, and review 9 previously reported cases of iliac artery dissection associated with FMD. A 30-year-old man had abdominal pain, and went into shock. Angiograms revealed dissection of the left common iliac artery with extravasation. At emergent surgery the rupture site was in the proximal left common iliac artery and extended to the left external iliac artery. Interposition of the diseased artery with a Dacron graft was attempted, but cardiac arrest occurred, and resuscitation was unsuccessful. Pathologic examination showed typical characteristics of diffuse medial FMD. Ten cases (5 male and 5 female patients), including the present case, with dissection of iliac arteries associated with FMD have been reported. Median patient age was 45 years (range, 29-56 years). Three of the 10 patients had acute onset of symptoms, and the remainder had gradual development of intermittent claudication or groin pain. Only the present case had evidence of rupture. The site of dissection was in the external iliac artery in 8 patients and the common iliac artery in 2 patients. Anatomic bypass or interposition of the diseased artery was performed in 8 patients; the others received conservative treatment. There was no mortality in the 9 previously reported cases. Fatal acute dissection and rupture of the common iliac artery occurred in a patient with FMD, even though the clinical course of this disease is relatively benign. FMD should be considered the cause of dissection and rupture of the iliac artery in a patient with symptoms but of non-atherosclerotic age.


Soluble form of Jagged1: unique product of epithelial keratinocytes and a regulator of keratinocyte differentiation.
Notch signaling pathway is an important regulator of epithelial differentiation. Recent studies have characterized multiple ligands, including Jagged1, as mediators of Notch signaling. In this work, an alternatively spliced transcript of Jagged1 was isolated in yeast two-hybrid screening through interaction with thrombospondin-1. This transcript, devoid of sequences encoding the transmembrane and intracellular domains of Jagged1, was specific for keratinocytes. Furthermore, the truncated Jagged1 polypeptide devoid of the intracellular domain was detected prominently in the suprabasal keratinocyte layer in neonatal epithelia. The soluble form of Jagged1, when expressed as a tagged polypeptide was efficiently secreted into the culture medium and the N-terminal signal sequence became cleaved off upon secretion. Direct contact between a cell presenting the transmembrane form of Jagged1 and a Notch-expressing cell has been proposed as a prerequisite for the signaling event. However, the soluble form of Jagged1, when present in the cell culture medium, was sufficient to induce keratinocyte differentiation. These observations suggest a novel mechanism of how Jagged1 can target cells beyond the direct cell-cell contact in developing epithelia.


Central alpha-adrenergic agonists and need-induced 3% NaCl and water intake.
In the present study, noradrenaline (NOR, alpha-non-specific adrenergic agonist), clonidine (CLO, alpha 2), phenylephrine (PHE, alpha 1) or isoproterenol (ISO, beta-agonist) was injected in the medial septal area (MSA) of water-deprived, sodium-deplete or food-deprived rats. NOR (80, 160 nmol) inhibited the intake of 3% NaCl, water deprivation-induced and meal-associated water intake. Food deprivation-induced food intake and 10% sucrose intake were not altered by NOR. CLO (10, 20, 30, 40 nmol) inhibited (80-100% inhibition compared to control during 60 min) the intake of 3% NaCl, water deprivation-induced and meal-associated water intake. CLO had a weaker inhibition on food and 10% sucrose intake (30-50% less than the control during 60 and 15 min, respectively). PHE (160 nmol) inhibited 3% NaCl intake and 10% sucrose intake (30% less than the control for 15-30 min). ISO (160 nmol) did not alter water or 3% NaCl intake. NOR induced an increase, CLO and ISO induced a decrease, and PHE no alteration in mean arterial pressure. NOR did not alter water or 3% NaCl intake when injected unilaterally into the caudate nucleus. The results suggest that NOR injected in the MSA acts on alpha 2-adrenergic receptors inducing a specific inhibition of 3% NaCl and water intake.


Perceived individual and community barriers in the provision of family planning services by lady health workers in Tehsil Gujar Khan.
To identify contextual barriers (social, cultural, geographic and economic), faced by Lady Health Workers (LHWs) and to assess their strategies at different levels (individual, community and system) in the provision of family planning services to their clients in Tehsil Gujar Khan. The mixed model cross-sectional study was conducted from April 1 to July 10, 2010, in Tehsil Gujar Khan, Punbjab, Pakistan. It was carried out in two phases: in the first phase 10 in-depth interviews were conducted with the workers, followed by two focus group discussions. On the basis of findings, a structured questionnaire was developed and administered to 111 workers in the second phase. Of the total, 97 responses were used for analysis. Data analysis was done by SPSS-16. Majority of the respondents reported barriers at the community level: religious barriers 69% (n = 67), sociocultural barriers 58% (n = 56), transport 54% (n = 52), communication and economic reasons 25% (n = 24). Individual level barriers were female gender, experience and low education. System-level barriers were increased workload, National immunization days/sub-national immunization days, late supply, stock shortage (especially injectables), problems for referred clients and lack of proper incentives. Lady health workers still face barriers at individual, family, community and system level in the delivery of Family Planning services.


Acute toxicity of Ag and CuO nanoparticle suspensions against Daphnia magna: the importance of their dissolved fraction varying with preparation methods.
A variety of methods to prepare nanoparticle suspensions have been employed for aquatic toxicity tests, although they can influence the dispersion property and subsequent toxicity of nanoparticles. Thus, in this study, we prepared stock suspensions of silver (Ag) and copper oxide (CuO) nanoparticles using different methods and compared their acute toxicity against Daphnia magna. The results showed that the dispersion method, filtration and initial concentration largely affected their toxicity, when the toxicity was expressed as the total concentrations of Ag and Cu. In case of Ag nanoparticles, the toxicity was also influenced by their different particle size. However, negligible differences in 24h-median effect concentration (EC(50)) values, which were calculated in terms of their dissolved concentrations, were observed. When expressing toxicity on the basis of dissolved concentrations, 24h-EC(50) values of the Ag and CuO nanoparticles were also found to be similar to those of the counterpart ionic species, i.e., Ag (as AgNO(3)) and Cu (as CuCl(2)·2H(2)O). These findings indicate that the dissolved fraction of nanoparticles largely contributes to their acute toxicity. Our results may help in establishing a useful guideline for preparing nanoparticle suspensions with reproducible toxicity.


Beneficial effects of yam on carbon tetrachloride-induced hepatic fibrosis in rats.
In a previous study, lyophilised yam reduced brain amyloid beta-protein (Abeta) accumulation and improved the antioxidative defence system in senescence-accelerated (SAMP8) mice. Therefore, the aim of this study was to investigate the hepatic protection of yam in the carbon tetrachloride-induced hepatic fibrosis of rats. Hepatic fibrosis was induced in rats via intraperitoneal injections of CCl(4) at a dose of 1 mL kg(-1) body weight (BW) twice weekly for 8 weeks. Three groups of rats were gavaged daily with yams at doses of 0.5, 1 and 2 g kg(-1) BW for 8 weeks, respectively. Yam treatments significantly decreased the ratio of liver/body weight, levels of gamma-glutaminotranspeptidase (GGT), low-density lipoprotein, and triglyceride in serum when compared with those administered CCl(4) alone. Treatment with yams significantly elevated antioxidant activities of glutathione peroxidase (GSH-Px) and superoxidase dismutase (SOD) in livers. Microscopically, yam-treated groups presented with low histoscores of CCl(4)-induced liver injury and fibrosis. Additionally, yam treatment reduced the area of GGT-positive foci and the index of proliferating cell nuclear antigen (PCNA) in liver. Daily administration of yam attenuates CCl(4)-induced hepatic fibrosis in rats in a dose-dependent manner; this attenuation may be related to the antioxidant properties of yams.


Antinociceptive action of NOP and opioid receptor agonists in the mouse orofacial formalin test.
Nociceptin/orphanin FQ (N/OFQ) modulates several biological functions, including pain transmission via selective activation of a specific receptor named NOP. The aim of this study was the investigation of the antinociceptive properties of NOP agonists and their interaction with opioids in the trigeminal territory. The orofacial formalin (OFF) test in mice was used to investigate the antinociceptive potential associated to the activation of NOP and opioid receptors. Mice subjected to OFF test displayed the typical biphasic nociceptive response and sensitivity to opioid and NSAID drugs. Mice knockout for the NOP gene displayed a robust pronociceptive phenotype. The NOP selective agonist Ro 65-6570 (0.1-1mgkg-1) and morphine (0.1-10mgkg-1) elicited dose dependent antinociceptive effects in the OFF with the alkaloid showing larger effects; the isobologram analysis of their actions demonstrated an additive type of interaction. The mixed NOP/opioid receptor agonist cebranopadol elicited potent (0.01-0.1mgkg-1) and robust antinociceptive effects. In the investigated dose range, all drugs did not modify the motor performance of the mice in the rotarod test. Collectively the results of this study demonstrated that selective NOP agonists and particularly mixed NOP/opioid agonists are worthy of development as innovative drugs to treat painful conditions of the trigeminal territory.


Promising approaches for the treatment and prevention of viral respiratory illnesses.
Viral respiratory tract infections are the most common human ailments, leading to enormous health and economic burden. Hundreds of viral species and subtypes have been associated with these conditions, with influenza viruses, respiratory syncytial virus, and rhinoviruses being the most frequent and with the highest burden. When considering prevention or treatment of viral respiratory tract infections, potential targets include the causative pathogens themselves but also the immune response, disease transmission, or even just the symptoms. Strategies targeting all these aspects are developing concurrently, and several novel and promising approaches are emerging. In this perspective we overview the entire range of options and highlight some of the most promising approaches, including new antiviral agents, symptomatic or immunomodulatory drugs, the re-emergence of natural remedies, and vaccines and public health policies toward prevention. Wide-scale prevention through immunization appears to be within reach for respiratory syncytial virus and promising for influenza virus, whereas additional effort is needed in regard to rhinovirus, as well as other respiratory tract viruses.


Comparison of early and late respondents to a postal health survey questionnaire.
We mailed a health survey to the 18,408 residents of a California retirement community and compared the 11,550 respondents on a number of characteristics by time of response. Early respondents were more likely to be the "worried well," that is, healthy individuals who see their doctor regularly, receive disease detection screening, and follow healthful life-style practices. Late respondents tended to answer questions regarding their mental function and emotional status more negatively. Early and late respondents did not differ in the rates of death or hospitalization during the first 5 years of the study; nonrespondents had a higher incidence of hospitalization than respondents in year 1 and higher death rates in the first 3 years, but not thereafter.


Thermal behaviors, combustion mechanisms, evolved gasses, and ash analysis of spent potlining for a hazardous waste management.
An unavoidable but reusable waste so as to enhance a more circular waste utilization has been spent potlining (SPL) generated by the aluminum industry. The combustion mechanisms, evolved gasses, and ash properties of SPL were characterized dynamically in response to the elevated temperature and heating rates. Differential scanning calorimetric (DSC) results indicated an exothermic reaction behavior probably able to meet the energy needs of various industrial applications. The reaction mechanisms for the SPL combustion were best described using the 1.5-, 3- and 2.5-order reaction models. Fluoride volatilization rate of the flue gas was estimated at 2.24%. The SPL combustion emitted CO2, HNCO, NO, and NO2 but SOx. The joint optimization of remaining mass, derivative thermogravimetry, and derivative DSC was achieved with the optimal temperature and heating rate combination of 783.5 °C, and 5 °C/min, respectively. Interaction between temperature and heating rate exerted the strongest and weakest impact on DSC and remaining mass, respectively. The fluorine mainly as the formation of substantial NaF and CaF2 in the residual ash. Besides, the composition and effect of environment of residual solid were evaluated. The ash slagging tendency and its mineral deposition mechanisms were elucidated in terms of turning SPL waste into a benign input to a circular waste utilization.


COX-2 overexpression increases motility and invasion of breast cancer cells.
Cyclooxygenase-2 (COX-2), an inducible enzyme involved in prostaglandin (including PGE(2)) biosynthesis, is overexpressed in several epithelial malignancies including breast cancer. We tested the hypothesis that COX-2 overexpression in breast cancer cells results in increased cell motility and invasion. COX-2 overproducing cells were generated by stable transfection of several human breast cancer cells with pSG5-COX2 vector. We confirmed the overexpression of COX-2 protein by western blotting, and by measuring PGE(2) in the medium with an immunoassay. We measured cell motility by counting the number of cells crossing an 8-micron pore size PET membrane, and cell invasion by counting the number of cells invading through a Matrigel-coated membrane that simulates basement membrane. COX-2 transfected MDA-231 cells produced 30-43-fold more PGE2 as compared to parental cells. COX-2 overexpression increased cell migration approximately 2.2-fold and cell invasion through Matrigel approximately 5.1-fold. Addition of 50 microM NS-398, a COX-2 inhibitor, inhibited Matrigel invasion of MDA-231 cells by 54% as compared to solvent confirming the role of COX-2 in cell invasion. It is known that an increase in cell migration and invasion can be brought about by cytoskeletal alterations and basement membrane degradation due to increased expression of pro-urokinase plasminogen activator (pro-uPA). To investigate the mechanism of our observed increase in cell invasion by COX-2, we found by western blotting that the level of pro-uPA was significantly higher (approximately 5-fold) in COX-2 transfected MDA-231 cells than untransfected MDA-231 cells. Similar to our observations in cell culture, we found evidence that increased COX-2 activity correlates with uPA in a mouse model of breast cancer metastasis to bone. In this study, we conclude that COX-2 overexpression in human breast cancer cells enhances cell motility and invasiveness thus suggesting a mechanism of COX-2 mediated metastasis.


Effects of Cell Temperature and Reactant Humidification on Anion Exchange Membrane Fuel Cells.
The performance of an anion exchange membrane fuel cell (AEMFC) under various operating conditions, including cell temperature and humidification of inlet gases, was systematically investigated in this study. The experimental results indicate that the power density of an AEMFC is susceptible to the cell temperature and inlet gas humidification. A high performance AEMFC can be achieved by elevating the cell operating temperature along with the optimization of the gas feed dew points at the anode and cathode. As excess inlet gas humidification at the anode is supplied, the flooding is less severe at a higher cell temperature because the water transport in the gas diffusion substrate by evaporation is more effective upon operation at a higher cell temperature. The cell performance is slightly affected when the humidification at the anode is inadequate, owing to dehydration of the membrane, especially at a higher cell temperature. Furthermore, the cell performance in conditions of under-humidification or over-humidification at the cathode is greatly reduced at the different cell temperatures tested due to the dehydration of the anion exchange membrane and the water shortage or oxygen mass transport limitations, respectively, for the oxygen reduction reaction. In addition, back diffusion could partly support the water demand at the cathode once a water concentration gradient between the anode and cathode is formed. These results, in which sophisticated water management was achieved, can provide useful information regarding the development of high-performance AEMFC systems.


Isolation of Bioactive Rotenoids and Isoflavonoids from the Fruits of Millettia caerulea.
Three new rotenoids (1-3), two new isoflavonoids (4 and 5), and six known analogues (6-11) were isolated from an n-hexane partition of a methanol extract of the fruits of Millettia caerulea, with the structures of the new compounds elucidated by analysis of their spectroscopic data. The relative configurations of the rotenoids were determined by interpretation of their NMR spectroscopic data, and their absolute configurations were established using electronic circular dichroism spectra and specific rotation values. All compounds isolated were evaluated for their cell growth inhibitory activity against the HT-29 human colon cancer cell line, and the known compounds, (-)-3-hydroxyrotenone (6) and (-)-rotenone (7), were found to be potently active. When tested in an NF-κB inhibition assay, compound 6 showed activity. This compound, along with the new compound, (-)-caeruleanone D (1), and the known compound, ichthynone (8), exhibited K-Ras inhibitory potency. Further bioactivity studies showed that the new compounds, (-)-3-deoxycaeruleanone D (2) and (-)-3-hydroxycaeruleanone A (3), and the known compounds 8 and 11 induced quinone reductase in murine Hepa 1c1c7 cells.


Bio-functionalized nickel-silica nanoparticles suppress bacterial leaf blight disease in rice (Oryza sativa L.).
Bacterial leaf blight (BLB) caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most devastative diseases that threatens rice plants worldwide. Biosynthesized nanoparticle (NP) composite compounds have attracted attention as environmentally safe materials that possess antibacterial activity that could be used in managing plant diseases. During this study, a nanocomposite of two important elements, nickel and silicon, was biosynthesized using extraction of saffron stigmas (Crocus sativus L.). Characterization of obtained nickel-silicon dioxide (Ni-SiO2) nanocomposite was investigated using Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), Transmission/Scanning electron microscopy (TEM/SEM), and energy-dispersive spectrum (EDS). Antibacterial activities of the biosynthesized Ni-SiO2 nanocomposite against Xoo were tested by measuring bacterial growth, biofilm formation, and dead Xoo cells. The bacterial growth (OD600) and biofilm formation (OD570) of Xoo treated with distilled water (control) was found to be 1.21 and 1.11, respectively. Treatment with Ni-SiO2 NPs composite, respectively, reduced the growth and biofilm formation by 89.07% and 80.40% at 200 μg/ml. The impact of obtained Ni-SiO2 nanocomposite at a concentration of 200 μg/ml was assayed on infected rice plants. Treatment of rice seedlings with Ni-SiO2 NPs composite only had a plant height of 64.8 cm while seedlings treated with distilled water reached a height of 45.20 cm. Notably, Xoo-infected seedlings treated with Ni-SiO2 NPs composite had a plant height of 57.10 cm. Furthermore, Ni-SiO2 NPs composite sprayed on inoculated seedlings had a decrease in disease leaf area from 43.83% in non-treated infected seedlings to 13.06% in treated seedlings. The FTIR spectra of biosynthesized Ni-SiO2 nanocomposite using saffron stigma extract showed different bands at 3,406, 1,643, 1,103, 600, and 470 cm-1. No impurities were found in the synthesized composite. Spherically shaped NPs were observed by using TEM and SEM. EDS revealed that Ni-SiO2 nanoparticles (NPs) have 13.26% Ni, 29.62% Si, and 57.11% O. Xoo treated with 200 µg/ml of Ni-SiO2 NPs composite drastically increased the apoptosis of bacterial cells to 99.61% in comparison with 2.23% recorded for the control. The application of Ni-SiO2 NPs significantly improved the vitality of rice plants and reduced the severity of BLB.


The sucrose transporter MdSUT4.1 participates in the regulation of fruit sugar accumulation in apple.
Sugar content is an important determinant of fruit sweetness, but details on the complex molecular mechanism underlying fruit sugar accumulation remain scarce. Here, we report the role of sucrose transporter (SUT) family in regulating fruit sugar accumulation in apple. Gene-tagged markers were developed to conduct candidate gene-based association study, and an SUT4 member MdSUT4.1 was found to be significantly associated with fruit sugar accumulation. MdSUT4.1 encodes a tonoplast localized protein and its expression level had a negative correlation with fruit sugar content. Overexpression of MdSUT4.1 in strawberry and apple callus had an overall negative impact on sugar accumulation, suggesting that it functions to remobilize sugar out of the vacuole. In addition, MdSUT4.1 is located on chromosomal region harboring a previously reported QTL for sugar content, suggesting that it is a candidate gene for fruit sugar accumulation in apple. MdSUT4.1 is involved in the regulation of fruit sugar accumulation in apple. This study is not only helpful for understanding the complex mechanism of fruit sugar accumulation, but it also provides molecular tools for genetic improvement of fruit quality in breeding programs of apple.


Low energy magnetic stimulation of the phrenic nerve - a simulation study.
Peripheral magnetic stimulation is a promising assistive technique for rehabilitation. Today's magnetic stimulation devices, designed for transcranial stimulation, operate at currents of 6 kA and higher. This makes them expensive and bulky. Many motor neurons in peripheral nerves are more accessible, have large diameters, and require significantly lower field strengths for stimulation. In this work, we present a simulation environment to determine the threshold current required to trigger an action potential in phrenic nerve motor neurons for different coil geometries. An anatomical model was used for coil placement and realistic field calculations. The field distribution was calculated using the finite integration technique and then applied to a neuronal model to simulate the axon membrane dynamics. For general applicability, the coil-nerve distance and the axon diameter were varied. We show that the required current was approximately 1.3 kA for a nerve-coil distance of 35 mm, which corresponds to 20% of the available power of a commercial TMS device. By including the nearby vagus nerve in the simulations, we showed that accidental stimulation of this nerve is highly unlikely. Our results pave the way for the development of smaller, less complex, and more affordable stimulators and promise to increase the use of peripheral magnetic stimulators in clinical settings.


Posterior lumbar interbody fusion versus circumferential fusion using the B-Twin expandable spinal system.
We reviewed the medical files of 32 patients with degenerative disc disease, spinal stenosis, and spondylolisthesis who underwent posterior lumbar interbody fusion using the B-Twin system. In 12 of these patients, posterior lumbar interbody fusion has been supplemented with posterior lumbar-instrumented fusion (circumferential fusion) because of spinal instability. Clinical and functional outcomes were assessed. The quality of fusion and disc height were recorded. The mean follow-up was 36 months (range, 18 to 42 months). At the latest examination, clinical improvement and fusion were statistically significant in both groups; the mean Oswestry disability index improved from 55% to 24%, and to 22% in the patients with more than 20 months follow-up; the mean Rolland-Morris disability questionnaire improved from 52% to 29% (p < 0.001); 95.6% (22/23) of the levels managed with the B-Twin system alone and 92.9% (13/14) of the levels managed with circumferential fusion showed solid fusion; and the intervertebral disc height increased from 8.1 +/- 0.74 mm to 11.4 +/- 0.93 mm in the B-Twin group and from 7.7 +/- 0.75 mm to 10.6 +/- 0.91 mm in the circumferential fusion group. However, in comparing the two groups there was no statistical significant difference. The B-Twin system is safe and effective for the management of degenerative disc disease as a stand-alone device. The combination with posterior lumbar-instrumented fusion systems for circumferential fusion yields statistically significant differences in fusion rate and functional outcome.


Assessment on homogeneity tests for kappa statistics under equal prevalence across studies in reliability.
In this paper, we assess the performance of homogeneity tests for two or more kappa statistics when prevalence rates across reliability studies are assumed to be equal. The likelihood score method and the chi-square goodness-of-fit (GOF) test provide type 1 error rates that are satisfactorily close to the nominal level, but a Fleiss-like test is not satisfactory for small or moderate sample sizes. Simulations show that the score test is more powerful than the chi-square GOF test and the approximate sample size required for a specific power of the former is substantially smaller than the latter. In addition, the score test is robust to deviations from the equal prevalence assumption, while the GOF test is highly sensitive and it may give a grossly misleading type 1 error rate when the assumption of equal prevalence is violated. We conclude that the homogeneity score test is the preferred method.


Observation of Network Dynamics of Ryanodine Receptors on Skeletal Muscle Sarcoplasmic Reticulum Membranes.
Rabbit muscle vesicles derived from sarcoplasmic reticulum were used as a material in studying networks of ryanodine receptors by cryo electron tomography. Three-dimensional analysis reveals the dynamical features of these networks. It was found that the connection angles were rotated along the transmembrane axis of ryanodine receptors. Majority of the connections was observed at domains 6/6 of ryanodine receptors while a small group of connections were showed at domains 9/10. The flexible rotation and connection shift seem to facilitate the extension of an annular network on the wall of the sarcoplasmic reticulum in a triad.


Electrical control of cell polarization in the fission yeast Schizosaccharomyces pombe.
Electric signals surround tissues and cells and have been proposed to participate in directing cell polarity in processes such as development, wound healing, and host invasion [1, 2]. The application of exogenous electric fields (EFs) can direct cell polarization in cell types ranging from bacteria and fungi to neurons and neutrophils [3-7]. The mechanisms by which EFs modulate cell polarity, however, remain poorly understood. Here we introduce the fission yeast Schizosaccharomyces pombe as a model organism to elucidate the mechanisms underlying this process. In these rod-shaped cells, an exogenous EF reorients cell growth in a direction orthogonal to the field, producing cells with a bent morphology. A candidate genetic screen identifies conserved factors involved in this process: an integral membrane proton ATPase pma1p that regulates intracellular pH, the small GTPase cdc42p, and the formin for3p that assembles actin cables. Interestingly, mutants in these genes still respond to the EF but orient in a different direction, toward the anode. In addition, EFs also cause electrophoretic movement of cell wall synthase complex proteins toward the anode. These data suggest molecular models for how the EF reorients cell polarization by modulating intracellular pH and steering cell polarity factors in multiple directions.


The research program at AIGLE.
The purpose of this work is to present the research program of a Clinical Center, the AIGLE Foundation in Buenos Aires, Argentina. It describes the potentialities and advantages of research in this context. It also describes the institute, the types of patients treated and its professional staff. The program covers four areas: determining the demand for psychotherapeutic care in the population at large, studying the conditions making participation in community mental health possible, analyzing and follow-up on the outcomes and studying the personal styles of the therapists. Finally, this work discusses the usefulness and applicability of these results for clinical practice.


Impacts of the COVID-19 pandemic on early pregnancy outcomes among women undergoing frozen-thawed embryo transfer: a retrospective cohort study.
The effect of COVID-19 pandemic on early pregnancy outcomes among women undergoing frozen-thawed embryo transfer (FET) remains unclear. We aimed to evaluate whether early pregnancy outcomes were altered in patients undergoing FET during the pandemic. In this retrospective cohort study, women conceived through FET in 2016-2021 from two hospitals in China were included. The early pregnancy outcomes were compared using Logistic regression model, including biochemical pregnancy rate (BPR), clinical pregnancy rate (CPR), and early pregnancy loss rate (EPLR). A total of 16,669 (67.2%) and 6,113 (26.8%) FET cycles enrolled before and during the pandemic, respectively. Univariate analyses showed that women undergoing FET during the pandemic had significantly increased BPR (72.9% vs. 69.7%) and CPR (59.5% vs. 55.0%), and significantly decreased EPLR (13.7% vs. 16.7%) compared to pre-pandemic (all P < 0.001). Moreover, after adjustment, the results were in accordance with univariate analysis for CPR [adjusted OR (95%CI) = 1.08 (1.01-1.14)] and EPLR [adjusted OR (95%CI) = 0.82 (0.73-0.91)], while the statistical significance between BPR and the pandemic disappeared. In summary, women conceived by FET did not have a reduced possibility of clinical pregnancy and a higher risk of early pregnancy loss during the pandemic compared with the pre-pandemic.


Clinical and hematological manifestations of visceral leishmaniasis in Yemeni children.
In southeast Yemen, visceral leishmaniasis (VL) is endemic in Lahj and Abyan and also in Hagga and Sadah, the areas lacking adequate diagnostic facilities. This study describes the clinical and hematological features in 64 cases of childhood VL. All children below 12 years of age who were managed as inpatient cases from 1 January to 31 December 2005 were included in this study. The diagnosis of VL was established by demonstration of leishmania parasites in bone marrow aspiration. Demographic information, physical signs at presentation and results of complete blood count were recorded and bone marrow aspirations were done for LD bodies. Mean age of the patients was 30 months, and there were 33 females and 31 males. Fever was seen in 100% of children with duration before diagnosis of 56 days. Splenomegaly was present in all cases and hepatomegaly in 84.4%, with mean enlargement of spleen and liver of 9.3 and 3.5 cm, respectively. Mean hemoglobin level, white blood cell and platelet counts were 6.6 g/dl, 3.58x109 /L and 71.7x109 /L, respectively. Absolute neutrophil count was <0.78x109 /L and mean reticulocyte count was 1.7%. Fever, hepatosplenomegaly and pancytopenia were the most common clinical and hematological manifestations in Yemeni children with VL.


Energy-dependent collision-induced dissociation study of buprenorphine and its synthetic precursors.
The collision-induced dissociation (CID) of protonated buprenorphine ([M+H](+) ) and four related compounds was studied by electrospray quadrupole/time-of-flight mass spectrometry (ESI-QTOF MS). The fragmentation pathways were investigated by using energy-dependent CID and pseudo-MS(3) (in-source CID combined with tandem mass spectrometry (MS/MS)) methods. The first steps of the fragmentation are the parallel losses of the substituents from the non-aromatic ring moieties. Depending on the applied collision energies, a large number of further fragment ions arising from the cross-ring cleavages of the core-ring structure were observed. Based on the experimental results, a generalized fragmentation scheme was developed for the five buprenorphine derivatives highlighting the differences for the alternatively substituted compounds. The collision-energy-dependent fragmentation profile of buprenorphine is visualized in a two-dimensional plot to aid its fingerprint identification.


A comprehensive approach to facilitating the recovery of cardiac surgery patients.
This article describes the cardiac surgery program at Baystate Medical Center. It emphasizes the importance of planning for the discharge process, early extubation, and structured activity guidelines and their effect on patient outcomes. The unique roles of the staff nurse, mid-level practitioner, and the clinical resource coordinator in facilitating the case management process are addressed.


Therapeutic enhancement: nursing intervention category for patients diagnosed with Readiness for Therapeutic Regimen Management.
To present a new nursing intervention category called therapeutic enhancement. Fewer than half of North Americans follow their physician's recommendations for diet and exercise, even when such are crucial to their health or recovery. It is imperative that nurses consider new ways to promote healthy behaviours. Therapeutic enhancement is intended to provide such a fresh approach. Traditional intervention techniques focusing on education, contracts, social support and more frequent interaction with physicians appear not to be effective when used alone. Successful strategies have been multidisciplinary; and have included interventions by professional nurses who assist patients to understand their disease and the disease process and that helps them to develop disease-management and self-management skills. Therapeutic enhancement incorporates The Stages of Change Theory, Commitment to Health Theory, Motivational Interviewing techniques and instrumentation specifically designed for process evaluation of health-promoting interventions. This is a critical review of approaches that, heretofore, have not been synthesised in a single published article. Based on the commonly used Stages of Change model, therapeutic enhancement is useful for patients who are at the action stage of change. Using therapeutic enhancement as well as therapeutic strategies identified in Stages of Change Theory, such as contingency management, helping relationships, counterconditioning, stimulus control and Motivational Interviewing techniques, nursing professionals can significantly increase the chances of patients moving from action to the maintenance stage of change for a specific health behaviour. Using the nursing intervention category, therapeutic enhancement can increase caregivers' success in helping patients maintain healthy behaviours.


Familiarity, orientation, and realism increase face uncanniness by sensitizing to facial distortions.
The uncanny valley predicts aversive reactions toward near-humanlike entities. Greater uncanniness is elicited by distortions in realistic than unrealistic faces, possibly due to familiarity. Experiment 1 investigated how familiarity and inversion affect uncanniness of facial distortions and the ability to detect differences between the distorted variants of the same face (distortion sensitivity). Familiar or unfamiliar celebrity faces were incrementally distorted and presented either upright or inverted. Uncanniness ratings increased across the distortion levels, and were stronger for familiar and upright faces. Distortion sensitivity increased with increasing distortion difference levels, again stronger for familiar and upright faces. Experiment 2 investigated how face realism, familiarity, and face orientation interacted for the increase of uncanniness across distortions. Realism increased the increase of uncanniness across the distortion levels, further enhanced by upright orientation and familiarity. The findings show that familiarity, upright orientation, and high face realism increase the sensitivity of uncanniness, likely by increasing distortion sensitivity. Finally, a moderated linear function of face realism and deviation level could explain the uncanniness of stimuli better than a quadratic function. A re-interpretation of the uncanny valley as sensitivity toward deviations from familiarized patterns is discussed.


Electromyographic responses of lower leg muscles to upward toe tilts as a function of age.
EMGs were recorded from the gastrocnemius and anterior tibialis muscles of 77 adult subjects in response to perturbation of stance by upward toe tilts. Subjects aged 22-88 y were initially grouped in seven decades (20s-80s). Each presented a history free of ear disease, eye disease not correctable by lenses, neurological disease, and persistent difficulty with balance or dizziness. All demonstrated functionally normal balance for their age on routine dynamic posturography. EMG recordings yielded onset and offset latencies, durations, and integrated amplitudes of the short and medium latency responses of the gastrocnemius and the long latency responses of the anterior tibialis. Analysis of the data revealed statistically significant left-right differences in amplitude of response and statistically significant height, gender, and age effects. Procedural issues were discussed; data were summarized for normative purposes; and suggestions were made for dealing with statistically significant differences in a clinical environment.


Two Cases of Sinonasal Non-Intestinal-Type Adenocarcinoma with Squamoid Morules Expressing Nuclear β-Catenin and CDX2: A Curious Morphologic Finding Supported by Molecular Analysis.
Sinonasal non-intestinal-type adenocarcinoma (non-ITAC) is a rare, morphologically diverse neoplasm of the head and neck. Squamoid morular metaplasia has recently been reported as an occasional finding in non-ITAC. Interestingly, these squamoid morules often show aberrant expression of CDX2 as well as nuclear expression of β-catenin, similar to other tumors that show this type of metaplasia, but the underlying mechanism responsible for this finding is not completely understood. We present two cases of low-grade non-ITAC with squamoid morules coexpressing CDX2 and nuclear β-catenin by immunohistochemistry, both of which were found to harbor a mutation in CTNNB1, the gene encoding β-catenin. This finding provides support that an alteration in the β-catenin pathway, including mutations in the β-catenin gene itself, is responsible for this recently described morphologic phenomenon in non-ITAC.


Complex wavefront reconstruction from multiple-image planes produced by a focus tunable lens.
We propose, through simulations and experiments, a wavefront reconstruction technique using a focus-tunable lens and a phase-retrieval technique. A collimated beam illuminates a complex object (amplitude and phase), and a diffuser then modulates the outgoing wavefront. Finally the diffracted complex field reaches the focus-tunable lens, and a CMOS camera positioned at a fixed plane registers the subjective speckle distribution produced by the lens (one pattern for each focal length). We have demonstrated that a tunable lens can replace the translation stage used in the conventional single-beam, multiple-intensity reconstruction algorithm. In other words, through iterations with a modified version of this algorithm, the speckle images produced by different focal lengths can be successfully employed to recover the initial complex object. With no movable elements, (speckle) image sampling can be performed at high frame rates, which is suitable for dynamical reconstruction applications.


Critical role of adsorption equilibria on the determination of surface-enhanced Raman enhancement.
Surface-enhanced Raman spectroscopy (SERS) is a useful technique for probing analyte-noble metal interactions and determining thermodynamic properties such as their surface reaction equilibrium constants and binding energies. In this study, we measure the binding equilibrium constants and Gibbs free energy of binding for a series of nitrogen-containing aromatic molecules adsorbed on Klarite substrates. A dual Langmuir dependence of the SERS intensity on concentration was observed for the six species studied, indicating the presence of at least two different binding energies. We relate the measured binding energies to the previously described SERS enhancement value (SEV) and show that the SEV is proportional to the traditional SERS enhancement factor G, with a constant of proportionality that is critically dependent on the adsorption equilibrium constant determined from the dual Langmuir isotherm. We believe the approach described is generally applicable to many SERS substrates, both as a prescriptive approach to determining their relative performance and as a probe of the substrate's affinity for a target adsorbate.


The high cost of prescription privileges.
This article presents some data regarding the costs in the augmentation of programs aimed at equipping psychologist to prescribe medications. Data are presented relative to the financial burden it will place on students, universities, internship sites, and the consumers of psychological services.


The Potential of Stem Cells in Treatment of Traumatic Brain Injury.
Traumatic brain injury (TBI) is a global public health concern, with limited treatment options available. Despite improving survival rate after TBI, treatment is lacking for brain functional recovery and structural repair in clinic. Recent studies have suggested that the mature brain harbors neural stem cells which have regenerative capacity following brain insults. Much progress has been made in preclinical TBI model studies in understanding the behaviors, functions, and regulatory mechanisms of neural stem cells in the injured brain. Different strategies targeting these cell population have been assessed in TBI models. In parallel, cell transplantation strategy using a wide range of stem cells has been explored for TBI treatment in pre-clinical studies and some in clinical trials. This review summarized strategies which have been explored to enhance endogenous neural stem cell-mediated regeneration and recent development in cell transplantation studies for post-TBI brain repair. Thus far, neural regeneration through neural stem cells either by modulating endogenous neural stem cells or by stem cell transplantation has attracted much attention. It is highly speculated that targeting neural stem cells could be a potential strategy to repair and regenerate the injured brain. Neuroprotection and neuroregeneration are major aspects for TBI therapeutic development. With technique advancement, it is hoped that stem cell-based therapy targeting neuroregeneration will be able to translate to clinic in not so far future.


Empirical antifungal therapy in treating febrile neutropenic patients.
Persistent or recurrent unexplained fever in neutropenic patients receiving antibiotics can be caused by invasive fungal infections, which are often difficult to diagnose. Early trials of empirical antifungal therapy with amphotericin B deoxycholate (AmB) documented reductions in the frequency of and the morbidity and mortality associated with invasive fungal infections. Because of AmB's infusional and renal toxicities, subsequent trials used newer, less toxic agents, such as the lipid formulations of AmB, the extended-spectrum azoles, and, more recently, the echinocandins. To date, alternatives to AmB have shown less toxicity, but improved efficacy has been less clear. Overall, empirical antifungal therapy can help prevent the morbidity associated with many fungal infections, eliminate concerns about diagnostic pitfalls, and prevent breakthrough undetected infections. However, its potential shortcomings are overtreatment, toxicity, and increased treatment-related costs when treatment is given to persons not needing it. Newer diagnostic tools are needed to target those most in need of antifungal therapy.


Five-year Experience With Arterial Switch Operation in the First Hours of Life.
We assessed morbidity after 2 management strategies for arterial switch operation (ASO) in a single institution: first hours of life surgery and conventional approach. From September 2009 to September 2014, 346 consecutive patients who underwent ASO were enrolled. The study group included 92 patients who underwent ASO in the first 24 hours after birth (group I). The control group consisted of 254 patients who underwent ASO after 24 hours of life in the conventional way (group II). Three outcomes were analyzed: postoperative ventilation time (VT), post-extubation hospital length of stay (peLOS), and a composite morbidity index, defined as postoperative VT + peLOS + occurrence of selected major complications. Overall 30-day survival was 98% (2 [2%] group I vs 5 [2%] group II, P = 1.000). Fifty (13.3%) major complications were observed: 14 (15%) in group I and 36 (15%) in group II (P = 0.635). Although peLOS and morbidity index did not differ significantly between groups, postoperative VT (42 hours [24, 67] vs 27 hours [22, 47], P = 0.008) and total hospital stay were significantly longer in group II (18 days [10, 19] vs 14 days [12, 18]). A median volume of 80 mL (60-100 mL) of autologous umbilical cord blood was collected (80 mL, group 1 vs 60 mL, group II; P = 0.090). Homologous blood cell transfusion was avoided in 70 patients (78%) in group I and in 13 patients (6%) in group II (P < 0.001). Arterial switch operation during the initial 24 hours of life has similar outcomes in view of morbidity and mortality to the conventional approach.


Different microvascular involvement in dermatomyositis and systemic sclerosis. A preliminary study by a tight videocapillaroscopic assessment.
To observe for changes in capillary morphology and architecture by tight sequential videocapillaroscopic (VCP) assessment in patients with dermatomyositis (DM) and systemic sclerosis (SSc). VCP examination was performed in 6 patients with DM and 9 with SSc, at baseline and after one month for three times. Four consecutive fields were examined bilaterally for any single finger (from 2nd to 5th). The best visible image per each digit was selected and images from baseline and follow-up were analysed as a sequence, to allow the same capillaries to be tracked and re-assessed. The following abnormalities were identified: homogeneous enlarged capillaries, giant capillaries, irregularly enlarged capillaries, microhaemorrhages, microaneurysms and neoangiogenesis. Capillary density was also considered. A significant progressive change of the following abnormalities was detected in DM patients with respect to SSc patients: microhaemorrhages (p=0.009), avascular areas (p=0.024), neoangiogenesis (p=0.001), microaneurysms (0.001), and irregular enlarged capillaries (p=0.044). No significant differences were found for homogeneous enlarged capillaries (p=0.140), giant capillaries (p=1.0) and hairpin/crossed capillaries (0.516). Our preliminary study demonstrated a rapid change of the capillary morphology and architecture in DM with respect to SSc patients. Additional investigations involving larger series of patients may be useful to support more strongly our observations.


Structure of glutamate decarboxylase from E. coli: spectral studies.
Structure of recombinant glutamate decarboxylase (GAD alpha) was studied by optical methods and electron microscopy. The active (pH 4.6) and inert (pH 6.3) holoGAD and apoGAD were investigated. Absorption and CD spectra were recorded in the range of 190 - 500 nm. Visible spectra were resolved into the bands corresponding to individual electron transitions using lognormal curves. The structures of predominant tautomers of internal aldimines were determined as ketoenamine at pH 4.6 and enolimine at pH 6.3. CD spectra show that holoGAD and apoGAD exhibit a negative band at 204 - 245 nm and a positive band near 190 - 204 nm. The contents of the secondary structure elements were estimated on the basis of the values of the mean residue ellipticity. Evidently, the main difference between the GAD forms studied is in the content of alpha-helix and random coil. HoloGAD has 50% of alpha-helix at pH 4.6 and 67% at pH 6.3, whereas apoGAD - 17 and 27%, respectively. Thus presented data establish the essential role of pyridoxal phosphate (PLP) in the organization of the GAD secondary structure due to tightening its polypeptide chain. It seems possible, that conformational changes induced by PLP binding stabilize the protein structure and promote the assembly of subunits into macromolecule, which was confirmed by electron microscopy.


Polyester meshes and adhesive materials in the brain: comparative research in rats to optimize surgical strategy.
The goal of this study was to determine the biocompatibility of polyester mesh electrode carriers for auditory brainstem implants with and without adhesives in a rat model. Physical properties of the meshes were evaluated within the fourth ventricle region, both without (Group A) and with adhesives (muscle, Group B; oxidized regenerated cellulose [ORC], Group C; and fibrin glue, Group D). The stability of the mesh position, the healing process, and host defense reaction after 2 to 60 days were examined in series of tissue sections in which meshes were preserved in situ. The cellular reaction was further evaluated using electron microscopy. Although otherwise pliable, polyester meshes were too rigid when used with adhesives, especially fibrin glue or muscle. Also, the sharp edges of the meshes presented a risk of brainstem and cerebellar lesions. Regardless of the material, meshes induced persistent inflammatory tissue reactions characterized by numerous macrophages and foreign-body giant cells. After 14 days, the cellular response had resulted in sufficient fibroblast and collagen fiber encapsulation of the meshes and remained essentially unchanged thereafter. No influence of adhesives on the healing process was observed, and, unexpectedly, these substances did not reduce the risk of dislocation prior to adequate cellular encasement. In some rats in Groups A and C, purulent inflammation, in part with Gram-positive bacteria, occurred after 2 to 14 days. The ORC exhibited persistent swelling, introducing the risk of occlusive hydrocephalus and/or brainstem compression. Polyester meshes and various adhesives exhibited acceptable biocompatibility in terms of local tissue reaction. Adhesives reduced pliability of the meshes, however, and were ineffective in reducing the risk of dislocation. Handling characteristics could be improved by better mesh designs, and risk of infection could be reduced by both improved designs and surface treatment of the meshes with antibacterial agents.


Spectroscopic characterization of flavin mononucleotide bound to the LOV1 domain of Phot1 from Chlamydomonas reinhardtii.
The absorption and emission behavior of flavin mononucleotide (FMN) in the light-, oxygen- and voltage-sensitive (LOV) domain LOV1 of the photoreceptor Phot1 from the green alga Chlamydomonas reinhardtii was studied. The results from the wild-type (LOV1-WT) were compared with those from a mutant in which cysteine 57 was replaced by serine (LOV1-C57S), and with free FMN in aqueous solution. A fluorescence quantum yield of phi(F) = 0.30 and a fluorescence lifetime of tau(F) = 4.6 ns were determined for FMN in the mutant LOV1-C57S, whereas these quantities are reduced to about phi(F) = 0.17 and tau(F) = 2.9 ns for LOV1-WT, indicating an enhanced intersystem crossing in LOV1-WT because of the adjacent sulfur of C57. A single-exponential fluorescence decay was observed in picosecond laser time-resolved fluorescence measurements for both LOV1-WT and LOV1-C57S as expected for excited singlet state relaxation by intersystem crossing and internal conversion. An excitation intensity dependent fluorescence signal saturation was observed in steady-state fluorescence measurements for LOV1-WT, which is thought to be because of the formation of a long-lived intermediate flavin-C(4a)-cysteinyl adduct in the triplet state (few microseconds triplet lifetime, adduct lifetime around 150 s). No photobleaching was observed for LOV1-C57S, because no thiol group is present in the vicinity of FMN for an adduct formation.


[Eye movement disturbances and working memory deficit in bipolar affective disorder].
THE AIM AND METHODS: The aim of this study was to assess the intensity and frequency of eye movement abnormalities measured with infrared reflectometry, and working memory disturbances assessed with the Wisconsin Card Sorting Test (WCST). The study was performed in 87 patients with bipolar affective illness, in 119 patients with schizophrenia and in 90 healthy persons. In patients, the assessment was done during a mild symptomatic period or in remission. In patients with bipolar affective illness significant disturbances of eye movement and working memory compared with healthy subjects were found. Frequency and intensity of fixation abnormalities was less intense compared to schizophrenic patients, while smooth pursuit abnormalities had a similar degree. Working memory disturbances in bipolar patients were, as to the ability of formulation of logical conception, of similar degree as in schizophrenia. On the other hand, as to the effectiveness of thinking, no difference compared with healthy controls was found. The results obtained suggest that eye movement and working memory disturbances may constitute neurophysiological and neuropsychological endophenotypic markers of bipolar affective illness what makes possible using them in molecular genetic studies of this illness.


The Poetry of Medicine.
Outlining an educational initiative for those who work in the National Health Service (NHS), this article argues that literary reflection has been too easily seen as a simple tool which may improve the practitioner's empathic skills and benefit patient-centred care. Using anecdotal feedback, the author reports ways in which a series of literary workshops held for professionals in the NHS have added to practitioners' general sense of well-being. Feedback shows that participants perceived literature in the workshop setting as being more than an enabler of 'empathy'. They reported that reflecting on literature in a group setting is an opportunity to think about their own autonomy, pleasure and creativity. The article concludes with a reflection about priorities in regulatory culture, its relationship to burnout, and ideas for future work.


Abdominoplasty improves quality of life, psychological distress, and eating disorder symptoms: a prospective study.
Background. Only some studies provide sufficient data regarding the effects of nonpostbariatric (aesthetic) abdominoplasty on various aspects of quality of life. Nevertheless, when considering the effects on eating habits, publications are lacking. Therefore we decided to assess the effects of nonpostbariatric abdominoplasty on eating disorder symptoms, psychological distress, and quality of life. Materials and Methods. 64 consecutive women underwent nonpostbariatric abdominoplasty. Three outcome measures were completed: the Eating Disorder Inventory (EDI), Raitasalo's modification of the Beck Depression Inventory (RBDI), and the 15D general quality of life questionnaire. Results. The mean age at baseline was 42 years and the mean body mass index (BMI) 26.4. Fifty-three (83%) women completed all the outcome measures with a mean follow-up time of 5 months. A significant improvement from baseline to follow-up was noted in women's overall quality of life, body satisfaction, effectiveness, sexual functioning, and self-esteem. The women were significantly less depressive and had significantly less drive for thinness as well as bulimia, and their overall risk of developing an eating disorder also decreased significantly. Conclusions. Abdominoplasty results in significantly improved quality of life, body satisfaction, effectiveness, sexual functioning, self-esteem, and mental health. The risk of developing an eating disorder is decreased significantly. This trial is registered with Clinicaltrials.gov NCT02151799.


Influence of drying time of polyelectrolyte multilayers on the compression-induced pattern formation.
Compression of the polyelectrolyte multilayers has been found previously when they were pressed by a poly(dimethylsiloxane) (PDMS) stamp under a small pressure (Macromolecules 2004, 37, 8836). In this work, we further found that the pattern formation of the poly(diallyldimethylammonium chloride) (PDADMAC) containing multilayers is dependent on the drying time of the multilayers prior to compression. After the poly(4-styrenesulfonic acid-co-maleic acid) sodium salt (PSSMA)/PDADMAC multilayers were dried at 70% relative humidity and room temperature for 2, 6, and 12 h, compression of the multilayers by a PDMS stamp with linear patterns obtained double strips, high ridges and linear patterns on the multilayers, respectively. These phenomena were independent of the layer number and salt concentration and could be applied to other PDADMAC containing multilayer systems such as poly(styrene sulfonate) sodium salt (PSS)/PDADMAC and poly(acrylic acid, sodium salt) (PAA)/PDADMAC. A model was suggested to depict the process, and the influence of the water content on the multilayer structure and properties was discussed. The stability experiments revealed that the strips and high ridges obtained at shorter drying time could be erased by incubation in water for 5 h, while the compression created patterns were very stable.


Multimorbidity, Depression, and Mortality in Primary Care: Randomized Clinical Trial of an Evidence-Based Depression Care Management Program on Mortality Risk.
Two-thirds of older adults have two or more medical conditions that often take precedence over depression in primary care. We evaluated whether evidence-based depression care management would improve the long-term mortality risk among older adults with increasing levels of medical comorbidity. Longitudinal analyses of the practice-randomized Prevention of Suicide in Primary Care Elderly: Collaborative Trial (PROSPECT). Twenty primary care practices randomized to intervention or usual care. The sample included 1204 older primary care patients completing the Charlson Comorbidity Index (CCI) and other interview questions at baseline. For 2 years, a depression care manager worked with primary care physicians to provide algorithm-based care for depression, offering psychotherapy, increasing the antidepressant dose if indicated, and monitoring symptoms, medication adverse effects, and treatment adherence. Depression status based on clinical interview, CCI to evaluate medical comorbidity, and vital status at 8 years (National Death Index). In the usual care condition, patients with the highest levels of medical comorbidity and depression were at increased risk of mortality over the course of the follow-up compared to depressed patients with minimal medical comorbidity [hazard ratio 3.02 (95% CI, 1.32 to 8.72)]. In contrast, in intervention practices, patients with the highest level of medical comorbidity and depression compared to depressed patients with minimal medical comorbidity were not at significantly increased risk [hazard ratio 1.73 (95% CI, 0.86 to 3.96)]. Nondepressed patients in intervention and usual care practices had similar mortality risk. Depression management mitigated the combined effect of multimorbidity and depression on mortality. Depression management should be integral to optimal patient care, not a secondary focus.


Purification and characterisation of cathepsin B mRNA 3'-untranslated-region-binding protein (CBBP), a protein that represses cathepsin B mRNA translation.
We reported that the 3'-untranslated region (3'-UTR) of cathepsin B mRNA of Sarcophaga peregrina (flesh fly) is necessary for the repression of its translation, and detected the 3'-UTR-binding protein in lysates of larval hemocytes in which cathepsin B mRNA translation was repressed [Yano, T., Kurata, S. & Natori, S. (1995) Eur. J. Biochem. 234, 39-43]. In this study, we purified the 3'-UTR-binding protein from an embryonic cell line of Sarcophaga. The purified protein (CBBP) was found to repress cathepsin B mRNA translation in a rabbit reticulocyte lysate. We found that the CBBP contents of the hemocytes did not change during metamorphosis, although the cathepsin B mRNA became translatable only at the pupal stage. Moreover, we found that pupal, but not larval hemocytes, contained a factor that inhibited the binding of CBBP to the 3'-UTR. A regulatory mechanism of cathepsin B expression in Sarcophaga hemocytes is discussed.


A novel RET fusion in non-small cell lung cancer identified by next-generation sequencing: a case report.
REarranged during Transfection (RET) gene fusion is one of the common oncogenic variants in non-small cell lung cancers (NSCLCs). However, few RET fusion-positive cases have partner intergenic-breakpoint fusions, in which the partner breakpoint localizes to intergenic regions. Here, we report a 40-year-old Chinese female non-smoker diagnosed with minimally invasive lung adenocarcinomas (pT1bN0M0, stage IA). Targeted next-generation sequencing revealed a rare form of RET fusion in the cancerous tissue, in which an intergenic fragment upstream multiple inositol-polyphosphate phosphatase 1 gene was fused with the tyrosine kinase domain in RET. The result was validated by fluorescence in situ hybridization. To our knowledge, this novel form of RET fusion in NSCLC is reported for the first time, which expands the alteration spectrum and paves the way for the future development of specific targeted therapies.


The narrow-leaf syndrome: a functional and evolutionary approach to the form of fog-harvesting rosette plants.
Plants that use fog as an important water-source frequently have a rosette growth habit. The performance of this morphology in relation to fog interception has not been studied. Some first-principles from physics predict that narrow leaves, together with other ancillary traits (large number and high flexibility of leaves, caudices, and/or epiphytism) which constitute the "narrow-leaf syndrome" should increase fog-interception efficiency. This was tested using aluminum models of rosettes that differed in leaf length, width and number and were exposed to artificial fog. The results were validated using seven species of Tillandsia and four species of xerophytic rosettes. The total amount of fog intercepted in rosette plants increased with total leaf area, while narrow leaves maximized interception efficiency (measured as interception per unit area). The number of leaves in the rosettes is physically constrained because wide-leafed plants can only have a few blades. At the limits of this constraint, net fog interception was independent of leaf form, but interception efficiency was maximized by large numbers of narrow leaves. Atmospheric Tillandsia species show the narrow-leaf syndrome. Their fog interception efficiencies were correlated to the ones predicted from aluminum-model data. In the larger xerophytic rosette species, the interception efficiency was greatest in plants showing the narrow-leaf syndrome. The adaptation to fog-harvesting in several narrow-leaved rosettes was tested for evolutionary convergence in 30 xerophytic rosette species using a comparative method. There was a significant evolutionary tendency towards the development of the narrow-leaf syndrome the closer the species grew to areas where fog is frequently available. This study establishes convergence in a very wide group of plants encompassing genera as contrasting as Tillandsia and Agave as a result of their dependence on fog.


The role of interventions in the cancer evolution-an evolutionary games approach.
We propose to endow evolutionary gamemodels with changes of the phenotypes adjustment during the transient generations performed by the parameters in the payoff matrix which determine the fitness resulting from different interactions between players. These changes represent an alteration of access to external resources which, in turn, may reflect anticancer treatment. In the case of spatial games, these functions are represented by an additional lattice where another and parallel game based on cellular automata is performed. The main assumption of the spatial games is that each cell on the lattice is represented by a player following only one strategy. We propose to consider cells on the spatial lattice as heterogeneous (instead of homogeneous), so that each particular player may contain mixed phenotypes. Spatial games of the type, proposed by us, are called multidimensional spatial evolutionary games (MSEG). It may happen that within the population, all of the players have diverse phenotypes (which probably better describes biological phenomena). The additional lattice representing the evolution of resources increases only the dimension of the lattice in the MSEG.


New library building: Mercer University School of Medicine, Macon, Georgia.
The Mercer University School of Medicine (MUSM) enrolled its charter class in 1982. The curriculum is problem-based and adaptable to the learning needs of each student. MUSM is housed in a new building designed to support this unique educational program. Its library is an example of a comparatively small, but fully functional, medical school library. The planning process, design, and layout of the new library facility are described. Among its unique features are an integrated print and non-print collection, current periodical display space, and extensive use of task lighting.


Analysis of Ionizing Radiation Induced DNA Damage by Superresolution dSTORM Microscopy.
The quantitative detection of radiation caused DNA double-strand breaks (DSB) by immunostained γ-H2AX foci using direct stochastic optical reconstruction microscopy (dSTORM) provides a deeper insight into the DNA repair process at nanoscale in a time-dependent manner. Glioblastoma (U251) cells were irradiated with 250 keV X-ray at 0, 2, 5, 8 Gy dose levels. Cell cycle phase distribution and apoptosis of U251 cells upon irradiation was assayed by flow cytometry. We studied the density, topology and volume of the γ-H2AX foci with 3D confocal microscopy and the dSTORM superresolution method. A pronounced increase in γ-H2AX foci and cluster density was detected by 3D confocal microscopy after 2 Gy, at 30 min postirradiation, but both returned to the control level at 24 h. Meanwhile, at 24 h a considerable amount of residual foci could be measured from 5 Gy, which returned to the normal level 48 h later. The dSTORM based γ-H2AX analysis revealed that the micron-sized γ-H2AX foci are composed of distinct smaller units with a few tens of nanometers. The density of these clusters, the epitope number and the dynamics of γ-H2AX foci loss could be analyzed. Our findings suggest a discrete level of repair enzyme capacity and the restart of the repair process for the residual DSBs, even beyond 24 h. The dSTORM superresolution technique provides a higher precision over 3D confocal microscopy to study radiation induced γ-H2AX foci and molecular rearrangements during the repair process, opening a novel perspective for radiation research.


Takayasu's arteritis in a pregnant woman. A case report.
Takayasu's arteritis in a pregnant white patient is described. This case highlights the fact that, irrespective of race, any patient who presents for the first time in pregnancy with pulseless hypertensive disease or other features suggestive of Takayasu's arteritis, should have their management in labour determined by the number of complications that are present. These are retinopathy, arterial aneurysms, hypertension and aortic regurgitation. These prognostic criteria will result in a classification of patients that will lead to appropriate management.