Three-layer guar gum matrix tablet formulations for oral controlled delivery of highly soluble trimetazidine dihydrochloride.
The present study is carried out to design oral controlled drug delivery systems for highly water-soluble drugs using guar gum as a carrier in the form of three-layer matrix tablets. Trimetazidine dihydrochloride was chosen as a model drug because of its high water solubility. Matrix tablet granules containing 30% (M1), 40% (M2) or 50% (M3) of guar gum were prepared by the wet granulation technique using starch paste as a binder. Three-layer matrix tablets of trimetazidine dihydrochloride were prepared by compressing on either side of guar gum matrix tablet granules of trimetazidine dihydrochloride M1, M2 or M3 with 200 mg of guar gum granules containing either 65% of guar gum (T1M1, T1M2 or T1M3), 75% of guar gum (T2M1, T2M2 or T2M3) or 85% of guar gum (T3M1, T3M2 or T3M3) as release retardant layers. The three-layer matrix tablets were evaluated for hardness, thickness, drug content uniformity, and were subjected to in vitro drug release studies. The amount of trimetazidine dihydrochloride released from the matrix and three-layer matrix tablets at different time intervals was estimated using a HPLC method. The three-layer guar gum matrix tablet (T3M3) provided the required release rate on par with the theoretical release rate for guar gum formulations meant for twice daily administration. The three-layer guar gum matrix tablet (T3M3) showed no change either in physical appearance, drug content or in dissolution pattern after storage at 40 degrees C/RH 75% for 6 months. The DSC study did not show any possibility of interaction between trimetazidine dihydrochloride and guar gum/other formulation excipients used in the study. The results indicated that guar gum, in the form of three-layer matrix tablets, is a potential carrier in the design of oral controlled drug delivery systems for highly water-soluble drugs such as trimetazidine dihydrochloride.


CD4+ T cells promote humoral immunity and viral control during Zika virus infection.
Several Zika virus (ZIKV) vaccines designed to elicit protective antibody (Ab) responses are currently under rapid development, but the underlying mechanisms that control the magnitude and quality of the Ab response remain unclear. Here, we investigated the CD4+ T cell response to primary intravenous and intravaginal infection with ZIKV. Using the LysMCre+Ifnar1fl/fl (myeloid type I IFN receptor-deficient) C57BL/6 mouse models, we identified six I-Ab-restricted ZIKV epitopes that stimulated CD4+ T cells with a predominantly cytotoxic Th1 phenotype in mice primed with ZIKV. Intravenous and intravaginal infection with ZIKV effectively induced follicular helper and regulatory CD4+ T cells. Treatment of mice with a CD4+ T cell-depleting Ab reduced the plasma cell, germinal center B cell, and IgG responses to ZIKV without affecting the CD8+ T cell response. CD4+ T cells were required to protect mice from a lethal dose of ZIKV after infection intravaginally, but not intravenously. However, adoptive transfer and peptide immunization experiments showed a role for memory CD4+ T cells in ZIKV clearance in mice challenged intravenously. These results demonstrate that CD4+ T cells are required mainly for the generation of a ZIKV-specific humoral response but not for an efficient CD8+ T cell response. Thus, CD4+ T cells could be important mediators of protection against ZIKV, depending on the infection or vaccination context.


Reversible generation of a carbon-centered radical from alkyl iodide using organic salts and their application as organic catalysts in living radical polymerization.
A new method of producing carbon-centered radicals was discovered through the reaction of an alkyl iodide (R-I) with organic salts to reversibly generate the corresponding alkyl radical (R(•)). Via this new reaction, the organic salts were used as new and highly efficient organic catalysts in living radical polymerization. The catalysts included common and inexpensive compounds such as tetrabutylammonium iodide and methyltributylphosphonium iodide. Notably, the catalysts were highly reactive. They enabled the synthesis of high-molecular-weight polymers (up to Mn = 140,000) and the control of acrylate polymerization, which had been difficult with other organic catalysts. The organic salt catalysts were highly versatile, reacting with methacrylate, acrylate, styrene, acrylonitrile, and functional methacrylate monomers. Well-defined block copolymers were also prepared by using this method. A kinetic study quantitatively confirmed the high reactivity of these catalysts. Attractive features of this system include its low cost, its ease of operation, and its ability to access a wide range of polymer designs.


A case delayed hemorrhage from the stump of the superior rectal artery after abdominoperineal resection of the rectum.
A 66-year-old man underwent abdominoperineal resection for advanced rectal cancer. On day 3 post surgery, a decompression tube was placed for postoperative ileus. Symptoms associated with ileus immediately disappeared. On day 7 post surgery, the patient vomited large amounts of fresh blood and became hemodynamically unstable. An emergency angiography revealed active bleeding from the stump of the superior rectal artery communicating with the third portion of the duodenum. Complete obliteration of the stump by proximal coil embolization was performed to achieve successful hemostasis. The postclinical course was uneventful and the patient was discharged on day 40 post surgery.


[Intrathoracic half-working heart and lung transplantation in the rat].
A new technique of intrathoracic half-working heart-lung transplantation in the rat was established. Donor heart-left lung graft was transplanted into left hemithorax of the recipient with aorta-aorta, bronchus-bronchus and superior vena cava (SVC)-SVC anastomoses, and the recipient's descending aorta proximal to the anastomosis was ligated. Five isografts (Lewis-Lewis) showed excellent cardiopulmonary function 4 weeks after transplantation. In 11 allografts (DA-Lewis), 5 rats without immunosuppression survived in 4-6 postoperative days and 6 rats with cyclosporine 10 mg/kg/day were alive during 8-14 days after operation. Nine of 11 allografts demonstrated moderate to severe (ISHLT grade 3-4) acute rejection and the grade of lung rejection was higher than that of heart rejection in 4 of 9 allografts.


Exosomes derived from gemcitabine-resistant cells transfer malignant phenotypic traits via delivery of miRNA-222-3p.
Although gemcitabine-based chemotherapy has been established as a core multimodal therapy for non-small cell lung cancer (NSCLC) treatment, its clinical efficacy remains limited by the development of acquired resistance following tumor metastasis and relapse. In this study, we investigated how gemcitabine-resistant (GR) cells contribute to the development of NSCLC tumor malignancy via exosome-mediated transfer of microRNAs. We first studied the mechanism of exosome internalization via PKH-67 staining and an immunofluorescence assay, then confirmed our finding by transmission electron microscopy and western blot analysis. Candidate miRNAs were identified through microarray analysis. Thereafter, RT-PCR, MTS, Transwell and soft agar assays were performed to assess the role of exosomic miR-222-3p in vitro. A 3' untranslated region reporter assay was applied to identify the target of miR-222-3p. A lung metastasis mouse model was constructed to evaluate tumor growth and metastasis in vivo. Finally, clinical samples were used for correlation analysis between exosomic miR-222-3p levels and patients' response to gemcitabine. A549-GR-derived exosomes were internalized by receipt cells via caveolin- and lipid raft-dependent endocytosis, which allowed the transfer of miR-222-3p. Exosomic miR-222-3p enhanced the proliferation, gemcitabine resistance, migration, invasion, and anti-anoikis of parental sensitive cells by directly targeting the promoter of SOCS3. In addition, a higher level of exosomic miR-222-3p in sera usually predicted worse prognosis in NSCLC patients. Our data demonstrate that exosomic-miR-222-3p functions as a principal regulator of gemcitabine resistance and malignant characteristics by targeting SOCS3. The exosomic miR-222-3p level in sera may be a potential prognostic biomarker for predicting gemcitabine sensitivity in NSCLC patients.


Postpublication criticism and the shaping of clinical knowledge.
Letters to the editor are an important means for ensuring accountability of authors and editors. They form a part of the postpublication peer review process. I studied the critical footprint made in the medical literature by 3 randomized trials (Hypertension Optimal Treatment [HOT], Captopril Prevention Project [CAPPP], and Swedish Trial in Old Patients with Hypertension 2 [STOP-2]) published in The Lancet and investigated the extent to which that footprint was preserved in shaping clinical knowledge. Qualitative appraisal of the criticism of each trial, taken from published letters. Agreed weaknesses and unanswered criticisms were identified from the authors' reply. I searched MEDLINE for practice guidelines published after the trial report and sought evidence for incorporation of criticism into these guidelines. From the time of publication to October 2000, HOT was cited in 9 of 36 practice guidelines; CAPPP, in 6 of 36; and STOP-2, not at all. HOT received 14 published criticisms, 5 comments, and 3 questions, of which 15 were responded to. Only 1 criticism, lack of power, was referred to in 1 guideline. CAPPP received 14 criticisms, 9 comments, and 3 questions, of which 8 were responded to. Only 1 criticism, imbalances between groups, was referred to in 1 guideline. STOP-2 received 12 criticisms, 9 comments, and 3 questions, of which only 6 were responded to. More than half of all criticism made in correspondence went unanswered by authors. Important weaknesses in trials were ignored in subsequently published practice guidelines. Failure to recognize the critical footprint of primary research weakens the validity of guidelines and distorts clinical knowledge.


Thymocyte development in the absence of pre-T cell receptor extracellular immunoglobulin domains.
Immature thymocytes express a pre-T cell receptor (pre-TCR) composed of the TCRbeta chain paired with pre-Talpha. Signals from this receptor are essential for passage of thymocytes through a key developmental checkpoint in the thymus. These signals were efficiently delivered in vivo by a truncated form of the murine pre-TCR that lacked all of its extracellular immunoglobulin domains. De novo expression of the truncated pre-TCR or an intact alphabetaTCR was sufficient to activate characteristic TCR signaling pathways in a T cell line. These findings support the view that recognition of an extracellular ligand is not required for pre-TCR function.


Generation of N-Heterocycles via Tandem Reactions of N '-(2-Alkynylbenzylidene)hydrazides.
As a powerful synthon, N '-(2-alkynylbenzylidene)hydrazides have been utilized efficiently for the construction of N-heterocycles. Since N '-(2-alkynylbenzylidene)hydrazides can easily undergo intramolecular 6-endo cyclization promoted by silver triflate or electrophiles, the resulting isoquinolinium-2-yl amides can proceed through subsequent transformations including [3 + 2] cycloaddition, nucleophilic addition, and [3 + 3] cycloaddition. Several unexpected rearrangements via radical processes were observed in some cases, which afforded nitrogen-containing heterocycles with molecular complexity. Reactive partners including internal alkynes, arynes, ketenimines, ketenes, allenoates, and activated alkenes reacted through [3 + 2] cycloaddition and subsequent aromatization, leading to diverse H-pyrazolo[5,1-a]isoquinolines with high efficiency. Nucleophilic addition to the in situ generated isoquinolinium-2-yl amide followed by aromatization also produced H-pyrazolo[5,1-a]isoquinoline derivatives when terminal alkynes, carbonyls, enamines, and activated methylene compounds were used as nucleophiles. Isoquinoline derivatives were obtained when indoles or phosphites were employed as nucleophiles in the reactions of N '-(2-alkynylbenzylidene)hydrazides. A tandem 6-endo cyclization and [3 + 3] cycloaddition of cyclopropane-1,1-dicarboxylates with N '-(2-alkynylbenzylidene)hydrazides was observed as well. Small libraries of these compounds were constructed. Biological evaluation suggested that some compounds showed promising activities for inhibition of CDC25B, TC-PTP, HCT-116, and PTP1B.


Establishment of HK-2 Cells as a Relevant Model to Study Tenofovir-Induced Cytotoxicity.
Tenofovir (TFV) is an antiviral drug approved for treating Human Immunodeficiency Virus (HIV) and Hepatitis B. TFV is administered orally as the prodrug tenofovir disoproxil fumarate (TDF) which then is deesterified to the active drug TFV. TFV induces nephrotoxicity characterized by renal failure and Fanconi Syndrome. The mechanism of this toxicity remains unknown due to limited experimental models. This study investigated the cellular mechanism of cytotoxicity using a human renal proximal tubular epithelial cell line (HK-2). HK-2 cells were grown for 48 h followed by 24 to 72 h exposure to 0-28.8 μM TFV or vehicle, phosphate buffered saline (PBS). MTT (MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) and Trypan blue indicated that TFV diminished cell viability at 24-72 h. TFV decreased ATP levels at 72 h when compared to vehicle, reflecting mitochondrial dysfunction. TFV increased the oxidative stress biomarkers of protein carbonylation and 4-hydroxynonenol (4-HNE) adduct formation. Tumor necrosis factor alpha (TNFα) was released into the media following exposure to 14.5 and 28.8 μM TFV. Caspase 3 and 9 cleavage was induced by TFV compared to vehicle at 72 h. These studies show that HK-2 cells are a sensitive model for TFV cytotoxicity and suggest that mitochondrial stress and apoptosis occur in HK-2 cells treated with TFV.


DIALYSIS FLASK FOR CONCENTRATED CULTURE OF MICROORGANISMS.
Gerhardt, Philipp (The University of Michigan, Ann Arbor), and D. M. Gallup. Dialysis flask for concentrated culture of microorganisms. J. Bacteriol 86:919-929. 1963.-A twin-chambered dialysis flask was designed with a supported membrane clamped between a reservoir of medium in the bottom and a small volume of culture above, the unit being mounted on a shaking machine to provide aeration and agitation. The performance of different dialysis membranes and membrane filters was compared in glucose-diffusion and bacterial-culture tests. Some of the variables in dialysis culture were assessed and the growth response was characterized, with Serratia marcescens as the test organism. The general usefulness and concentrating effect of dialysis culture were demonstrated in trials with 16 representative types of microorganisms. Dialysis culture was shown to be especially suitable for producing dense populations of cells or their macromolecular products in an environment free from complex medium constituents, for removing toxic products that limit growth or fermentation, and for supplying oxygen by diffusion without the damage from usual aeration procedures.


Ancestral protein resurrection and engineering opportunities of the mamba aminergic toxins.
Mamba venoms contain a multiplicity of three-finger fold aminergic toxins known to interact with various α-adrenergic, muscarinic and dopaminergic receptors with different pharmacological profiles. In order to generate novel functions on this structural scaffold and to avoid the daunting task of producing and screening an overwhelming number of variants generated by a classical protein engineering strategy, we accepted the challenge of resurrecting ancestral proteins, likely to have possessed functional properties. This innovative approach that exploits molecular evolution models to efficiently guide protein engineering, has allowed us to generate a small library of six ancestral toxin (AncTx) variants and associate their pharmacological profiles to key functional substitutions. Among these variants, we identified AncTx1 as the most α1A-adrenoceptor selective peptide known to date and AncTx5 as the most potent inhibitor of the three α2 adrenoceptor subtypes. Three positions in the ρ-Da1a evolutionary pathway, positions 28, 38 and 43 have been identified as key modulators of the affinities for the α1 and α2C adrenoceptor subtypes. Here, we present a first attempt at rational engineering of the aminergic toxins, revealing an epistasis phenomenon.


Adductor Branch of Terminal Divisions of the Ulnar Nerve Transfer to the Thenar Motor Branch in a High Median Nerve Palsy: A Case Report.
The author reports a 4-month-old high median nerve palsy in a 19-year-old man with right forearm fractures, stabilized with dynamic compression plates and screws. Surgical exploration revealed a large median nerve neuroma in the midarm that was excised, and the gap was bridged with sural nerve cable grafts. The extensor carpi radialis nerve was transferred to the anterior interosseous nerve in the forearm. The adductor branch of terminal divisions of the ulnar nerve was transferred to the thenar branch of the median nerve in the hand. The adductor branch of ulnar nerve transfer to the thenar motor branch in high median nerve palsy efficiently restored thumb opposition in 10 months of follow-up. In addition, the patient's grasp and pinch improved, preserving thumb adduction.


Biospecific adsorption of lysozyme onto monoclonal antibody ligand immobilized on nonporous silica particles.
It is very important to understand the equilibrium and dynamic characteristics of biospecific adsorption (affinity chromatography) for both scientific and application purposes. Experimental equilibrium and dynamic column data are presented on the adsorption of lysozyme onto antibody immobilized on nonporous silica particles. The Langmuir model is found to represent the equilibrium experimental data satisfactorily, and the equilibrium association constants and heats of adsorption have been estimated for two systems with different ligand densities. The effects of nonspecific interactions are more pronounced in the system with low-density ligand. The dynamic interaction kinetic parameters are estimated by matching the predictions of a fixed-bed model with the experimental breakthrough curves. The agreement between theory and experiment is good for the initial phases of breakthrough, where the mechanism of biospecific adsorption is dominant. In the later phase (saturation neighborhood) of breakthrough, the effects of nonspecific interactions appear to be greater in the low-density ligand system. The kinetics of the nonspecific interactions were estimated from the data of the later phase of breakthrough and were found to be considerably slower than those attributed to biospecific adsorption.


[Study on cytotoxicity to leukemia cell and enhancement of immunologic functions of jiexinkang].
Cytotoxicity to leukemia cell and enhancement of immunologic functions of jiexinkang (JXK, traditional Chinese medicine) were observed in 34 cases of leukemia in vitro. The results showed that the leukemia cytotoxicity in the group of vincristine combined with JXK was significantly higher than that in vincristine alone. It was also found among all the observed cases that 20 refractory or recurred patients resistant to vincristine showed an obvious intention of the anti-toxicity efficiency when JXK was added. Jiexinkang alone had anti-leukemia cell effect, too. We explored JXK effects on immunologic functions in mice, and found that IFNr and NK activities of normal and experimental model mice were significantly higher than those of control group(P < 0.01). The results indicate that JXK has an effect of anti-leukemia cell and may improve the cell-immunologic functions.


Developing and applying heterogeneous phylogenetic models with XRate.
Modeling sequence evolution on phylogenetic trees is a useful technique in computational biology. Especially powerful are models which take account of the heterogeneous nature of sequence evolution according to the "grammar" of the encoded gene features. However, beyond a modest level of model complexity, manual coding of models becomes prohibitively labor-intensive. We demonstrate, via a set of case studies, the new built-in model-prototyping capabilities of XRate (macros and Scheme extensions). These features allow rapid implementation of phylogenetic models which would have previously been far more labor-intensive. XRate 's new capabilities for lineage-specific models, ancestral sequence reconstruction, and improved annotation output are also discussed. XRate 's flexible model-specification capabilities and computational efficiency make it well-suited to developing and prototyping phylogenetic grammar models. XRate is available as part of the DART software package: http://biowiki.org/DART.


[Therapeutic management of peritonitis].
Antibiotherapy is a fundamental for the treatment of peritonitis. It may be used before surgery or as a complementary treatment after. Experimental models have demonstrated that infections are both aerobic and anaerobic. During the first stage, septicemic with a high death rate, the infection is due to enterobacteria, mostly Escherichia coli. Between D5 and D7 in surviving animals, there is a second stage with abscesses due to anaerobic bacteria, mostly Bacteroides fragilis. The antibiotic treatment must include these two types of bacteria in its spectrum. The role of Enterococcus faecalis is not clearly defined, but this bacterium must be taken into account in case of organ failure or associated septic shock. Treatment options for secondary peritonitis may be, according to severity, cefoxitin, an Augmentin + gentamycin combination, Tazocillin, or ertapenem. The reference treatment for nosocomial or tertiary peritonitis is the imipenem + amikacin combination. An antifungal treatment (fluconazole) is usually necessary, at least until the results of peritoneal fluid culture are available. The duration of treatment is quite variable, ranging from 48 h in less severe forms to 14 days.


Photochemical Reaction Between 1,2-Naphthoquinone and Adenine in Binary Water-Acetonitrile Solutions.
The photochemical reaction between 1,2-naphthoquinone (NQ) and adenine was investigated using nanosecond time-resolved laser flash photolysis. With photolysis at 355 nm, the lowest triplet state T1 of NQ was produced via intersystem crossing from its singlet excited state. The triplet-triplet absorption of the state contributes three bands of transient spectra at 374, 596 and 650 nm, respectively, in pure acetonitrile and binary water-acetonitrile solutions. In the presence of adenine, the observation of A·+ (at 363 nm) and NQ+H· radical (at 343 and 485 nm) indicates a multistep mechanism of electron transfer process followed by a proton transfer between 3 NQ* and adenine. By fitting with the Stern-Volmer relationship, the quenching rate constant kq of 3 NQ* by adenine in binary water-acetonitrile solutions (4/1, volume ratio, v/v) is determined as 1.66 × 109 m-1 s-1 . Additionally, no spectral evidence confirms the existence of electron transfer between 3 NQ* with thymine, cytosine and uracil.


Polarized cosmological gravitational waves from primordial helical turbulence.
We show that helical turbulence produced during a first-order phase transition generates circularly polarized cosmological gravitational waves (GWs). The characteristic frequency of these GWs for an extreme case of the phase transition model is around 10(-3)-10(-2) Hz with an energy density parameter as high as 10(-12)-10(-11). The possibility of detection is briefly discussed.


Interleukin-1 alpha mediates phorbol ester-induced inflammation and epidermal hyperplasia.
The topical application of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) to murine skin produces acute inflammatory and hyperplastic responses that have been associated with the promotion stage of skin carcinogenesis. It has been shown in a previous study that TPA induces the expression of the highly inflammatory cytokine, interleukin (IL) -1 alpha, in the epidermis of SENCAR mice. The goal of this study was to investigate the role of IL-1 alpha in several TPA-induced responses in skin. Topical application of TPA (1 microgram) enhanced the production of immunoreactive IL-1 alpha protein, primarily associated with the suprabasal keratinocytes. IL-1 alpha intradermally injected in the dorsal surface significantly increased (P < 0.001) vascular permeability at low concentrations (1-1000 microU) and increased (P < 0.001) inflammatory cell infiltration and epidermal hyperplasia at higher concentrations (10(3) U). TPA produced fourfold increases in vascular permeability as measured by Evans blue dye leakage; this effect was prevented by intradermal injection of anti-IL-1 alpha antibody (25-75 micrograms). Furthermore, injected anti-IL-1 alpha antibody significantly reduced (P < 0.001) TPA-induced inflammatory cell infiltration and epidermal hyperplasia. This study suggests that IL-1 alpha directly or indirectly mediates the inflammatory and hyperplastic responses elicited by topical treatment with TPA.


Muscular strength and physical function in elderly adults 6-18 months after a 12-week resistance exercise program.
Benefits of resistance exercise in elderly people are well documented; however, sustaining these benefits can be difficult and adherence is often poor. Muscular strength and physical function usually decline after a supervised resistance exercise program (REP). We investigated these changes in older adults during an observational follow-up and whether leisure time physical activity (LTPA) or unsupervised resistance exercise (RE) limit these changes. Subjects (N = 236, 73.7 ± 5.7 years, 58.2% female) had participated in a supervised 12-week REP. Quadriceps strength and timed-up-and-go performance (TUG) at follow-up were compared to values before and after REP. Multivariate statistics were used to predict changes in strength or function. Two hundred and eleven (90.3%) participants completed REP and 149 (63.1%) completed follow-up (11.4 ± 2.9 months). Quadriceps strength at follow-up decreased significantly compared to after REP (-27N), but was higher than before REP (+ 30N). TUG did not decrease during follow-up and was better than before REP (-0.9 seconds). LTPA (+ 38.0N, p < 0.001) and RE (+31.6N, p = 0.006) predicted strength at follow-up, although they did not completely prevent loss of strength during follow-up. quadriceps strength declines after a 12-week resistance exercise program in older adults. Neither LTPA nor RE completely prevents loss of quadriceps strength during follow-up, although they limited the loss. TUG did not change during follow-up and was better at follow-up than before the start of the resistance exercise program.


Growth of hydrophilic CuS nanowires via DNA-mediated self-assembly process and their use in fabricating smart hybrid films for adjustable chemical release.
Facile growth of CuS nanowires through self-assembly and their application as building blocks for near-infrared light-responsive functional films have been demonstrated. It is found that DNA is a key factor in preparing the CuS material with defined nanostructure. An exclusive oriented self-aggregate growth mechanism is proposed for the growth of the nanowires, which might have important implications for preparing advanced, sophisticated nanostructures based on DNA nanotechnology. By employing the hydrophilic CuS nanowire as an optical absorber and thermosensitive nanogel as guest reservoir inside alginate film, a new platform for the release of functional molecules has been set up. In vitro studies have shown that the hybrid film possesses excellent biocompatibility and the release rate of chemical molecules from the film could be controlled with high spatial and temporal precision. Our novel approach and the resulting outstanding combination of properties may advance both the fields of DNA nanotechnology and light-responsive devices.


Linking Psychological Capital and Behavioral Support for Change: The Roles of Openness to Change and Climate for Innovation.
Employees' behavioral support for change is seen as a key factor for the success of organizational changes. Given the assumed importance, the study developed a multilevel conditional mediation model and examined whether psychological capital influences behavioral support for change and if so, how the effect occurs. Results from a sample of 69 team leaders and 319 followers showed that the positive impact of psychological capital on openness to change was stronger in teams high in climate for innovation and that the mediating role played by openness to change in the relationship of psychological capital to behavioral support for change was significant when climate for innovation was high.


[Allergic phenomena in the course of dermatomycoses].
Fungi, well known as infectious factors so far, are important allergens too. A fungal id reaction is defined as a distant skin manifestation of an established fungal infection. The most typical setting is in association with tinea of the feet. The main id reactions are well established. A widespread lichen trichophyticus--eruption of small follicular papules grouped or diffuse. The eruption is symmetrical, usually pronounced on the trunk but in severe cases extending down to the lower limbs, even sometimes involving the face. The common cause of this type of id reaction is scalp ringworm of kerion type, caused typically by Trichophyton verrucosum. The treatment of the original ringworm lesion may play a role in initiation of the process. A pompholyx-like id affecting the interdigital spaces and palmar surfaces of the fingers, the palms and sometimes the dorsal surfaces of the hands. This eruption is associated with an acute inflammatory tinea of the feet and may develop spontaneously or as a result of inappropriate treatment. The palmar and web space skin may be covered with papules or vesicles. Sometimes blisters or pustules may occur. Other varieties of mycides include eczematous eruptions, erysipelas-like dermatitis, psoriasiform dermatitis, erythema multiforme, erythema annulare centrifugum, erythema nodosum, and urticaria. Adequate antifungal therapy is recommended as the treatment of allergic diseases caused by superficial fungi.


Using plant status data for off-site emergency management: technical and political aspects.
Subsequent to the TMI and Chernobyl accidents, emergency management is investigating the possibility of taking balanced decisions on interventions as early as possible. This process relies more and more on in-plant data to assess the term of releases. The paper discusses the regulatory aspects of the communication related to the source term between the utility and the national authorities, and the authorities of a host country and neighbouring countries that may be affected. The technical aspects of the assessment process are summarised, with the emphasis on the handling of uncertainties. Notwithstanding the technical progress, the main dilemma for the decision makers remains the same. Risk management and prevention measures become more familiar to authorities. Utilities and national authorities have to get rid of complexes with respect to accidents covered by the accepted residual risk. International emergency management has to look for an organisation type ensuring the continuity of countermeasures independent of the presence of administrative borders, and with respect to national autonomies.


Differences in mechanism of action between current and future antidepressants.
Antidepressants are divided into several classes on the basis of their pharmacologic mechanisms of action, which are thought to be responsible for both their therapeutic actions and their side effect profiles. All classes currently available in the United States affect serotonin, norepinephrine, and/or dopamine neurotransmission. New agents in development also affect neurotransmission of such monoamines and include serotonin-norepinephrine reuptake inhibitors, serotonin-selective agents, selective monoamine oxidase inhibitors, and selective norepinephrine reuptake inhibitors. Treatments with entirely new mechanisms of action are also being studied, including hormone-linked treatments such as estrogen replacement therapy and the steroid antagonist mifepristone (RU-486 or C-1073); novel antagonist peptides such as corticotropin-releasing factor, neurokinins, and injectable pentapeptides; and agents that affect glutamate neurotransmission. The introduction of antidepressants with novel mechanisms of action could potentially revolutionize the treatment of depression.


Formation of stripelike flux patterns obtained by freezing kinematic vortices in a superconducting Pb film.
We demonstrate experimentally and theoretically that the dissipative state of superconducting samples with a periodic array of holes at high current densities consists of flux rivers resulting from a short-range attractive interaction between vortices. This dynamically induced vortex-vortex attraction results from the migration of quasiparticles out of the vortex core (kinematic vortices). We have directly visualized the formation of vortex chains by scanning Hall probe microscopy after freezing the dynamic state by a field cooling procedure at a constant bias current. Similar experiments carried out in a sample without holes show no hint of flux river formation. We shed light on this nonequilibrium phenomena modeled by time-dependent Ginzburg-Landau simulations.


Blockade of the reward-potentiating effects of nicotine on lateral hypothalamic brain stimulation by chlorisondamine.
Chlorisondamine, a quarternary nicotinic antagonist, was given in a dose that crosses the blood-brain barrier, is taken up and concentrated intracellularly by dopaminergic neurons, and induces long-term blockade of the locomotor stimulant and rewarding effects of nicotine. This treatment had no effect on the rewarding effects of lateral hypothalamic brain stimulation, failing to shift the function that relates reward strength to rate of responding (rate-frequency function). That the treatment regimen was sufficient to block nicotinic receptors in the reward system was confirmed by the fact that it completely blocked the ability of normally effective nicotine to potentiate the rewarding effects of stimulation (shift this function to the left). These data add evidence that the direct, endogenous cholinergic contribution to brain stimulation reward is muscarinic and fit with other evidence that the potentiation of brain stimulation reward by exogenous nicotine involves actions on nicotinic receptors native to dopaminergic neurons.


A Rare Case of Kartagener Syndrome Presenting with Sinusitis, Situs Inversus, and Bronchiectasis: Emphasizing Early Diagnosis and Management Strategies.
Primary ciliary dyskinesia (PCDs), a subset of ciliary motility disorders, includes the rare hereditary illness Kartagener syndrome (KS). Sinusitis, situs inversus, and bronchiectasis, brought on by aberrant ciliary activity, are its defining features. We describe a case of an 18-year-old female with a history of recurrent respiratory complaints and chronic sinusitis. Additional testing confirmed the diagnosis of KS by identifying situs inversus, chronic bronchiectasis, and nasal polyps. This instance emphasizes the value of prompt KS diagnosis and treatment to avoid consequences. Supportive pulmonary care, antibiotics, and chest physical therapy are frequently employed, despite the lack of therapeutic standards. To further understand and manage this illness, more research is required. Patients with recurrent respiratory infections and structural lung disease can identify KS early.


A Jehovah's Witness Adolescent in the Labor and Delivery Unit: Should Patient and Parental Refusals of Blood Transfusions for Adolescents Be Honored?
A 15-year-old was admitted to the labor and delivery unit for induction of a 41-week-gestation pregnancy. Her parents, members of Jehovah's Witnesses, and the patient, who had been studying the religion but had not yet been baptized, were adamant that no blood transfusions would be accepted even if a life-threatening hemorrhage were to occur. In our analysis, we examine the underlying ethical conflict and issues raised by this case. We considered two important ethical questions in analyzing the dilemma: first, whether adolescents are capable of providing autonomous and authentic refusals for lifesaving interventions; and second, whether parents can refuse such interventions for their adolescent children based on their religious beliefs. We provided justifications for not considering the adolescent's refusal as autonomous and for overruling the parental refusal, concluding that there was ethical support for providing potentially lifesaving transfusions should they become clinically indicated. We also suggested strategies to avoid blood loss and the need for transfusions in order to respect the stated values and preferences of the patient and her family to the greatest degree possible. In order to protect the privacy of the patient and her family, details in this case have been changed and no identifiable information has been used.


Human Body Mechanics of Pushing and Pulling: Analyzing the Factors of Task-related Strain on the Musculoskeletal System.
The purpose of this review is to name and describe the important factors of musculoskeletal strain originating from pushing and pulling tasks such as cart handling that are commonly found in industrial contexts. A literature database search was performed using the research platform Web of Science. For a study to be included in this review differences in measured or calculated strain had to be investigated with regard to: (1) cart weight/ load; (2) handle position and design; (3) exerted forces; (4) handling task (push and pull); or (5) task experience. Thirteen studies met the inclusion criteria and proved to be of adequate methodological quality by the standards of the Alberta Heritage Foundation for Medical Research. External load or cart weight proved to be the most influential factor of strain. The ideal handle positions ranged from hip to shoulder height and were dependent on the strain factor that was focused on as well as the handling task. Furthermore, task experience and subsequently handling technique were also key to reducing strain. Workplace settings that regularly involve pushing and pulling should be checked for potential improvements with regards to lower weight of the loaded handling device, handle design, and good practice guidelines to further reduce musculoskeletal disease prevalence.


Does hand calculator use explain why university students cannot perform elementary arithmetic?
In a sample of German students (125 women, 128 men) only 26.3% answered 10 mathematics problems in the D'Amore Test, fewer than Standing, et al. reported. Significant correlations were found for test and self-predicted scores but predictors were not the same in the two studies. Although there were no sex differences, women were more accurate in the mental calculations, especially if they rarely used calculators.


Natural killer cell activity in reticulum-cell sarcomas of SJL/J mice. II. Analysis of RCS-associated NK activity.
Lymphoid cells taken from the grossly enlarged lymph nodes (LN) and spleens of SJL/J mice bearing transplantable reticulum-cell sarcomas (RCS), showed increased levels of natural killer (NK) cell activity, when compared to LN and spleen cells taken from normal SJL mice. The NK susceptible target cells used for these studies included RLmale-1 and YAC-1. Target cells that were not susceptible to NK lysis by CBA/J effector cells (high NK strain) were also resistant to lysis by RCS tumor cells. Although significant lysis of target cells was detectable at 4 h, optimal NK cytotoxicity was observed in a 16-h 51Cr-release assay. In terms of lytic units (LU)/10(7) effector cells, greater NK activity was observed in RCS effectors than was apparent in normal CBA/J lymphoid cells. Depletion of macrophages from RCS cell preparations had no effect on the observed NK activity. Purified Mu-IFN-alpha stimulated a small increase in the NK activity expressed by SJL lymphoid cells; however RCS-derived supernatants (containing Mu-IFN-gamma) did not augment NK activity of SJL effector cells, nor were they cytotoxic for NK target cells, Therefore, tumor-derived soluble factors appear not to be involved in the observed RCS-associated NK activity. The data presented in this report further define the parameters of the NK activity manifested by RCS tumor cell preparations. The accompanying article characterizes the nature of the NK effector cells present within RCS tumors of SJL mice. Taken together, these data indicate that the RCS tumors represent either neoplastic expansion of conventional NK cells with somewhat modified properties, or else an entirely new class of cytotoxic effector cells.


Evidence for pluripotent stem cell origin of idiopathic myelofibrosis: clonal analysis of a case characterized by a N-ras gene mutation.
Three cases of idiopathic myelofibrosis were screened for the presence of mutations at codon 12, 13, or 61 of the ras gene family by a rapid method based on polymerase chain reaction and hybridization to mutation-specific oligonucleotides. PB cells of one patient showed a point mutation at codon 12 of the N-ras oncogene. This molecular genetic hallmark was used to investigate the clonal relationship of different cell lineages by cell separation analysis. Presence of the N-ras 12 mutation in granulocytes, monocytes, B cells, and T lymphocytes, as well as erythroblasts, indicates that idiopathic myelofibrosis originates from a pluripotent stem cell, at least in this patient.


Discovery of the first pincer wasp (Hymenoptera, Dryinidae) from Rovno amber.
Dryinidae (Hymenoptera: Chrysidoidea) are recorded for the first time from Rovno amber (Ukraine), following the discovery of one female of Dryinus janzeni Olmi. Holotypes of D. balticus (Olmi) and D. bruesi (Olmi) previously assigned to the Baltic amber, were actually collected on the coast of Denmark, so that they have to be recorded as specimens in Scandinavian (Danish) amber. As a result, true records of Dryinus species of group 3 (Olmi 1993) in Baltic amber are three: D. janzeni, D. bruesi, because of a second specimen found in true Baltic amber, and D. velteni Olmi. Dryinidae are the 33th hymenopteran family known from Rovno amber. Three species, D. janzeni, D. bruesi and D. balticus are known from understudied Rovno and Scandinavian amber originated from the warmer south coast of the Subparathetys. Dryinus janzeni is the 115th hymenopteran species known from Rovno amber and the first Dryinus record from Ukraine.


Immunohistochemical expression of CD117 in borderline, low- and high-grade ovarian surface epithelial tumours: A clinicopathological study.
Ovarian cancer is one of leading causes of cancer related death in gynecology. CD117 is a tyrosine kinase receptor that plays an important role in regulation of apoptosis, cell proliferation and adhesion by binding to its ligand-stem cell factor. Recent studies demonstrated its aberrant overexpression in various malignancies and concluded that it may play a pivotal role in carcinogenesis. To evaluate CD117 expression in ovarian surface epithelial tumours. This retrospective study included 30 ovarian epithelial borderline, low and highly malignant tumours' formalin-fixed paraffin-blocks (FFPE) tissue blocks. Tissue sections were subjected to the routine haematoxylin-eosin stain and with the anti-CD117 immunohistochemically. There is a high significant difference in CD117 expression between borderline and malignant groups (P = 0.001). Additionally, there was significant difference in expression in relation to histopathological type (serous versus non-serous) in low-grade and the high-grade ovarian surface epithelial tumours (p=0.04, p=0.035 respectively). Tumour grade and stage strongly correlates with CD117 expression (p=0.014, p=0.019 respectively). We concluded that CD117 expression was significantly correlated with higher ovarian tumour grade and stage.


[High expression of human FIX(hFIX) in transgenic mice directed by goat beta-casein gene promoter].
To probe the feasibility of efficient production of human clotting factor IX(hFIX) with the approach of mammary gland bioreactor of transgenic animals, we constructed hFIX mammary gland expression vector containing promoter, exon 1, intron 1 and exon 2 of the goat beta-casein gene about 6.7 kb fragment as well as full-length of hFIX cDNA and its modified intron 1 sequence. By using transgenic products and 12 transgenic founders (9 female, 3 male) were produced, and the integration rate thus was 11.2%. ELISA assay and Western blot showed that the milk of 8 female transgenic mice had hFIX expression with high clotting activities. The highest hFIX expression in the milk of one transgenic mouse reached 52.9 mg/L, and the highest clotting activity of the transgene milk was 279.2%. FISH experiments indicated that hFIX DNA was integrated in different chromosomes in different mice. This result indicated that the hFIX mammary gland expression vector based on the goat beta-casein promoter can efficiently direct high expression of hFIX gene in the milk of transgenic mice, which maintained high clotting activity.


Hypersensitivity reaction to high-dose methotrexate and methotrexate-induced acral erythema in a child with acute lymphoblastic leukemia.
A 9-year-old boy with acute lymphoblastic leukemia experienced a hypersensitivity reaction (HSR) and acral erythema upon receiving high-dose methotrexate (HDMTX). Both HSR and acral erythema are uncommon adverse events of MTX therapy, and MTX has not been reported to cause HSRs in specific ethnic groups. We assessed the severity of each symptom and were successful in managing these adverse events for continuing subsequent HDMTX therapies. HSR appeared during the first and second HDMTX courses. Acral erythema occurred after the second and fourth courses. Desensitization by reducing the infusion rate and premedication allowed the continuation of HDMTX. Acral erythema improved with supportive care without dose reduction or interval lengthening. HSRs to MTX should be considered even during the first course. MTX-induced acral erythema is a self-limited reaction; therefore, the chemotherapeutic regimen should not be modified unless necessary.


Patient-Reported Outcome Assessments as Endpoints in Studies in Infectious Diseases.
The goal of administering medical interventions is to help patients live longer or live better. In keeping with this goal, there has been increasing interest in taking the "voice" of the patient into account during the development process, specifically in the evaluation of treatment benefits of medical interventions, and use of patient-centered outcome data to justify reimbursement. Patient-reported outcomes (PROs) are outcome assessments (OAs) used to define endpoints that can provide direct evidence of treatment benefit on how patients feel or function. When PROs are appropriately developed, they can increase the efficiency and clinical relevance of clinical trials. Several PROs have been developed for OA in specific infectious diseases indications, and more are under development. PROs also hold promise for use in evaluating adherence, adverse effects, satisfaction with care, and routine clinical practice.


4-hour urinary and serum immunofluorimetric assay for luteinizing hormone to detect onset of preovulatory LH surge.
The initial surge of LH is an important preovulatory event. The validity of a time-resolved immunofluorimetric assay method for determining LH both on the samples of serum and urine are reported in our study. A good correlation exists between the serum and urinary LH with the presence of a shorter interval in the length of the LH increase in the urinary dosage in respect to the serum dosage. There emerges when comparing the RIA and IFMA techniques that a good correlation exists both in the urinary and in the serum samples. However the values found with the IFMA method are on the average inferior (ca. 50%) in respect to those obtained with the RIA technique.


Sulforaphane and 2-oxohexyl isothiocyanate induce cell growth arrest and apoptosis in L-1210 leukemia and ME-18 melanoma cells.
Flow cytometry and laser-scanning confocal microscopy were used to study the effect of sulforaphane (SFN) and 2-oxohexyl isothiocyanate on the growth and viability of mouse leukemia L-1210 and human melanoma ME-18 cells during their exponential growth. Sulforaphane belongs to a group of compounds known as isothiocyanates. Isothiocyanates mainly occur in Cruciferous family. In particular, they occur in many vegetables such as broccoli and their sprouts. SFN and 2-oxohexyl isothiocyanate are potent inducers of detoxication phase 2 enzymes in mouse tissues and murine hepatoma cells in culture. Sulforaphane was shown to induce cell growth arrest in a dose dependent manner, followed by cell death. Sulforaphane induced the cell death via an apoptotic process. Two markers of apoptosis were investigated: phosphatidylserine externalization, which occurs in the early stages of apoptosis, and DNA strand breaks. Our results strongly suggest of chemopreventive activity toward cancer by the induction of apoptosis by SFN and 2-oxohexyl isothiocyanate.


Endotoxin-tobramycin additive toxicity on renal proximal tubular cells in culture.
Aminoglycoside-induced renal damage is enhanced in animals with Escherichia coli pyelonephritis. Bacterial endotoxin is liberated during antibiotic therapy. The toxic effect of endotoxin and tobramycin, alone or in combination, was investigated in primary cultures of rabbit proximal tubular cells grown to confluence in serum-free medium. Sodium-dependent uptakes of Pi and alpha-methylglucopyranoside (MGP) and enzymatic activities (lactate dehydrogenase [LDH] released as a marker of cell necrosis and gamma-glutamyltransferase [GGT] and N-acetyl-beta-D-glucosaminidase [NAG] present in the homogenate as markers of brush border membrane and lysosome integrity) were measured. Cells were exposed to (i) endotoxin (20 mg/liter), tobramycin (1 mM), or endotoxin plus tobramycin for 48 h, or (ii) endotoxin (100 mg/liter), tobramycin (4 mM), or endotoxin plus tobramycin for 72 h. Endotoxin alone did not alter Pi uptake, but tobramycin inhibited Pi uptake through a decrease in Vmax. The effect was not enhanced by the combination of endotoxin and tobramycin. Endotoxin and tobramycin alone exerted no significant effect upon MGP uptake, but strong inhibition of the Vmax was observed after exposure to a combination of endotoxin plus tobramycin, without alteration of the Km. Endotoxin decreased residual GGT activity in the cell homogenate. Tobramycin increased LDH release in the medium and NAG activity in the homogenate. Endotoxin plus tobramycin resulted in an additive effect upon LDH and NAG activities. In conclusion, by disturbing apical membrane integrity, endotoxin increased tobramycin toxicity in vitro in the absence of serum hormonal mediator.


Treatment of chronic fatigue syndrome by dietary supplementation with omega-3 fatty acids--a good idea?
Minor alterations of immune, neuroendocrine, and autonomic function may be associated with the chronic fatigue syndrome. omega-3 fatty acids decrease the production of putative mediators of inflammation, including interleukin-1, and tumor necrosis factor. Since interleukin-1 and tumor necrosis factor are the principal polypeptide mediators of immunoregulation, reduced production of these cytokines by dietary supplementation with omega-3, may be a possible mechanism for the treatment of chronic fatigue syndrome.


A registry for Dravet syndrome: The Italian experience.
We describe the Residras registry, dedicated to Dravet syndrome (DS) and to other phenotypes related to SCN1A mutations, as a paradigm of registry for rare and complex epilepsies. Our primary objectives are to present the tools and framework of the integrative platform, the main characteristics emerging from the patient cohort included in the registry, with emphasis on demographic, clinical outcome, and mortality. Standardized data of enrolled pediatric and adult patients were collected in 24 Italian expert centers and regularly updated at least on a yearly basis. Patients were prospectively enrolled, at registry starting, but historical retrospective data were also included. At present, 281 individuals with DS and a confirmed SCN1A mutation are included. Most patients have data available on epilepsy (n = 263) and their overall neurological condition (n = 255), based on at least one follow-up update. Median age at first clinical assessment was 2 years (IQR 0-9) while at last follow-up was 11 years (IQR 5-18.5). During the 7-year activity of the registry, five patients died resulting in a mortality rate of 1.84 per 1000-person-years. When analyzing clinical changes over the first 5-year follow-up, we observed a significant difference in cognitive function (P < 0.001), an increased prevalence of behavioral disorders including attention deficit (P < 0.001), a significant worsening of language (P = 0.001), and intellectual disability (P < 0.001). The Residras registry represents a large collection of standardized national data for the DS population. The registry platform relies on a shareable and interoperable framework, which promotes multicenter high-quality data collection. In the future, such integrated platform may represent an invaluable asset for easing access to cohorts of patients that may benefit from clinical trials with emerging novel therapies, for drug safety monitoring, and for delineating natural history. Its framework makes it improvable based on growing experience with its use and easily adaptable to other rare and complex epilepsy syndromes.


Involvement of endothelial nitric oxide synthase gene variants in the aggressiveness of uterine cervical cancer.
To date, few studies explore the involvement of endothelial nitric oxide synthase (eNOS) gene variants in uterine cervical cancer. Therefore, we conducted this study to assess the clinical implication of eNOS in cervical carcinogenesis, clinicopathological characteristics and patient survival. One hundred and seventeen patients with cervical invasive cancer and 95 with preinvasive lesions and 330 control women were consecutively enrolled. Real time polymerase chain reaction was used to examine the genotypic distributions of eNOS single nucleotide polymorphisms (SNPs) rs1799983 (894G>T) at the exon 7 region and rs2070744 (-786T>C) at the promoter region. Our results indicated no significant associations among genotypic distributions of eNOS SNPs and patients with cervical invasive cancer and those with preinvasive lesions as well as normal controls. However, cervical cancer patients with genotypes TC/CC in eNOS SNP rs2070744 carried less risk of advanced stage [odds ratios (OR) = 0.30, 95% confidence interval (CI)=0.09-0.97, p=0.036], parametrium invasion (OR=0.16, 95% CI=0.02-0.75, p=0.009) and pelvic lymph node metastasis (OR=0.12, 95% CI=0.01-0.89, p=0.016). In conclusion, although eNOS SNPs rs2070744 and rs1799983 do not display significant associations with cervical carcinogenesis and patient survival, cervical cancer patients with genotypes TC/CC in rs2070744 carry less risk of advanced stage, parametrium invasion and pelvic lymph node metastasis in Taiwan.


The inhibitor protein of the cAMP-dependent protein kinase-catalytic subunit interaction. Parameters of complex formation.
The formation of a complex between the catalytic subunit of the cAMP-dependent protein kinase and the Inhibitor Protein of this enzyme has been examined by means of nondenaturing gel electrophoresis. Two forms of complex were identified, both containing a 1:1 molar ratio of the component proteins. The formation of the major of the two forms is markedly enhanced by the presence of nucleotide triphosphate and divalent cation. Either Mg2+ or Mn2+ serves to promote complex formation. With Mg2+, only ATP is effective for enhancing complex formation, whereas with Mn2+ complex formation occurs to an equal extent with ATP, GTP, ITP, and adenyl-5'-yl imidodiphosphate. The formation of the two complexes is only minimally dependent upon nucleotide triphosphate. It is suggested that the two types of complex are a result of different species of catalytic subunit. Two principal forms of the complex have been detected occurring maximally in approximately a 2.5:1 ratio. In the accompanying paper (Fletcher, W.H., Van Patten, S.M., Cheng, H-C., and Walsh, D.A. (1986) J. Biol. Chem. 261, 5504-5513), we have described the use of a fluoresceinated derivative of catalytic subunit as a cytochemical probe to localize the Inhibitor Protein and the regulatory subunit of the protein kinase. The integrity of this fluorophore has been further characterized using the method of examining catalytic subunit-Inhibitor Protein interaction delineated here.


Expression of the Embryonic Cancer Stem Cells' Biomarkers SOX2 and OCT3/4 in Oral Leukoplakias and Squamous Cell Carcinomas: A Preliminary Study.
Cancer stem cells (CSCs) are incriminated for initiating the process of carcinogenesis either de novo or through the transformation of oral potentially malignant disorders (OPMDs) to oral squamous cell carcinoma (OSCC). The aim of this study was to detect the expression of embryonic-type CSC markers OCT3/4 and SOX2 in OSCCs and oral leukoplakias (OLs), the most common of OPMDs. The study type is experimental, and the study design is characterized as semiquantitative research, which belongs to the branch of experimental research. The experiment was conducted in the Department of Oral Medicine/Pathology, School of Dentistry, Aristotle University of Thessaloniki, Greece. This study focuses on the semiquantitative immunohistochemical (IHC) pattern of expression of CSCs protein-biomarkers SOX2 and OCT3/4, in paraffin embedded samples of 21 OSCCs of different grades of differentiation and 30 cases of OLs with different grades of dysplasia, compared to five cases of normal oral mucosa in both terms of cells' stain positivity and intensity. Statistical analysis was performed through SPSS 2017 Pearson Chi-square and the significance level was set at 0.05 (p=0.05). The expression of the respective genes of SOX2 and OCT3/4 was studied through quantitative polymerase chain reaction (qPCR), in paraffin-embedded samples of 12 cases of OLs with mild/non dysplasia and 19 cases moderately/poorly differentiated OSCCs(n=19) and five normal mucosa using the Independent Paired T-test. The genes SOX2 and Oct3/4 were expressed in all examined cases although no statistically significant correlations among normal, OL and OSCC, were established. A nuclear/membrane staining of OCT3/4 was noticed only in three out of 21 OSCCs but in none of OLs or normal cases (without statistical significance). A characteristic nuclear staining of SOX2 was noticed in the majority of the samples, mostly in the basal and parabasal layers of the epithelium. SOX2 was significantly detected in the OSCCs group (strong positivity in 17/21) than in the OL group (30 cases, mostly mildly stained) (p-value=0.007), and the normal oral epithelium (mild stained, p=0.065). Furthermore, SOX2 was overexpressed in well differentiated OSCCs group (5/OSCCs, strongly stained) rather than in mildly dysplastic and non-dysplastic OLs samples (14/OLs, mildly stained) (p-value =0.035). The characteristic expression of SOX2 but not of OCT3/4 in OLs' and OSCCs' lesions suggests the presence of neoplastic cells with certain CSC characteristics whose implication in the early stages of oral tumorigenesis could be further evaluated. The clinical use of SOX2, as prognostic factor, requires further experimental evaluation in larger number of samples.


Deregulation of microRNA-155 and its transcription factor NF-kB by polychlorinated biphenyls during viral infections.
Polychlorinated biphenyls (PCBs), and similar environmental contaminants, have been linked to virus outbreaks and increased viral induced mortality since the 1970s. Yet the mechanisms behind this increased susceptibility remain elusive. It has recently been illustrated that the innate immune viral detection system is tightly regulated by small non-coding RNAs, including microRNAs (miRNAs). For virus infections miRNA-155 expression is an important host response against infection, and deregulation of this miRNA is closely associated with adverse outcomes. Thus, we designed a targeted in vitro study using primary chicken fibroblasts, first exposed to a mixture of PCBs (Arochlor-1250) before being stimulated with a synthetic RNA virus (poly I:C), to determine if PCBs have the potential to deregulate miRNA-155. In this paper, we provide the first data for the deregulation of miRNA-155 when a host is exposed to a mixture of PCBs before a virus infection. Thus, we provide important evidence that PCBs can be involved in the deregulation of important miRNA pathways involved in the immune system; thereby demonstrating novel insights into the mechanism of PCB toxicity on the immune system.


Heterogeneous Fenton-like discoloration of Rhodamine B using natural schorl as catalyst: optimization by response surface methodology.
A cationic dye, Rhodamine B (RhB), could be efficiently discolored by heterogeneous Fenton-like reaction catalyzed by natural schorl. In this work, with the main goal of the optimization for RhB discoloration, central composite design under the response surface methodology (RSM) was employed for the experiment design and process optimization. The significance of a second-order polynomial model for predicting the optimal values of RhB discoloration was evaluated by the analysis of variance and 3D response surface and counter plots for the interactions between two variables were constructed. The Pareto graphic analysis of the discoloration process indicated that, among all the variables, solution pH (X 3, 47.95 %) and H2O2 concentration (X 1, 24.39 %) had the largest influences on the heterogeneous Fenton-like discoloration of RhB. Based on the model prediction, the optimum conditions for RhB discoloration were determined to be 45 mM H2O2 concentration, 2.5 g/L schorl dosage, solution pH 2, and 110 min reaction time, with the maximum RhB discoloration ratio of 98.86 %. The corresponding experimental value of RhB discoloration ratio under the optimum conditions was determined as 99.31 %, which is very close to the optimized one, implying that RSM is a powerful and satisfactory strategy for the process optimization.


Shape Estimation of Soft Manipulator Using Stretchable Sensor.
The soft robot manipulator is attracting attention in the surgical fields with its intrinsic softness, lightness in its weight, and safety toward the human organ. However, it cannot be used widely because of its difficulty of control. To control a soft robot manipulator accurately, shape sensing is essential. This paper presents a method of estimating the shape of a soft robot manipulator by using a skin-type stretchable sensor composed of a multiwalled carbon nanotube (MWCNT) and silicone (p7670). The sensor can be easily fabricated and applied by simply attaching it to the surface of the soft manipulator. In its fabrication, MWCNT is sprayed on a teflon sheet, and liquid-state silicone is poured on it. After curing, we turn it over and cover it with another silicone layer. The sensor is fabricated with a sandwich structure to decrease the hysteresis of the sensor. After calibration and determining the relationship between the resistance of the sensor and the strain, three sensors are attached at 120° intervals. Using the obtained data, the curvature of the manipulator is calculated, and the entire shape is reconstructed. To validate its accuracy, the estimated shape is compared with the camera data. We experiment with three, six, and nine sensors attached, and the result of the error of shape estimation is compared. As a result, the minimum tip position error is approximately 8.9 mm, which corresponded to 4.45% of the total length of the manipulator when using nine sensors.


Current psychopathology in previously assaulted older adults.
Older adult women age 55+ years (N = 549) were interviewed as part of a population-based epidemiological research study of lifetime experiences with physical and sexual assault and current mental health problems. Although overall rates of psychopathology were low, producing very small cells for comparison, women who reported experiencing physical assault an average of 28 years previously were more likely to present with past year substance abuse, depression, and avoidance and reexperiencing symptoms of posttraumatic stress disorder (PTSD) than those with no previous physical or sexual assault. Women who reported experiencing sexual assault an average of 50 years previously were more likely to present with autonomic arousal and avoidance symptoms of PTSD than those with no prior sexual assault. The aforementioned findings should be considered with caution, however, as sample cell sizes were minimal for all but the PTSD symptom subtypes. Mental health service implications for older adults are discussed.


[Recent progress in ALS research: ALS and TDP-43].
Selective involvements of upper and lower motor neurons have been regarded as one of the most characteristic features of amyotrophic lateral sclerosis (ALS). However, evidences of more extensive involvements affecting the systems other than the pure motor systems have been accumulated since the discovery of ubiquitin-positive inclusions (UbIs) in ALS, ALS-dementia (ALS-D), and frontotemporal lobar degeneration (FTLD) with UbIs (FTLD-U). A breakthrough occurred in ALS research in October 2006, when TAR DNA-binding protein43 (TDP-43) was identified as the core protein that is ubiquitinated in the cytoplasm, neurites and nucleus as UbIs. Antibody to phosphorylated TDP-43 selectively reacts to the inclusions and Western blotting demonstrates abnormal bands of phosphorylated TDP-43 in the brains of patients with ALS/FTLD-U. Similar findings were observed in ALS/parkinsonism-dementia complex (PDC) of Guam and Kii peninsula. These diseases are lumped in the "TDP-43 proteinopathy". In early 2008, several mutations of the TDP-43 gene were identified as the causative gene of autosomal-dominant familial ALS without SOD1 gene mutations. These findings suggest that abnormalities of TDP-43 directly or indirectly produce severe motor neuron degeneration. TDP-43 is thus one of the key proteins causing TDP-43 proteinopathies such as ALS, ALS-D, FTLD-U, and ALS/PDC of Guam and Kii. New revolutionary developments on ALS research for molecular mechanism and therapy are expected.


Improved glucose metabolism in mice lacking alpha-tocopherol transfer protein.
Conflicting evidence suggests a possible role for vitamin E in mammalian glucose metabolism and the protection from type 2 diabetes. The alpha-tocopherol transfer protein (alpha-TTP) mediates the transfer of alpha-tocopherol (alpha-TOH) from hepatocytes to very-low-density lipoproteins, thereby controlling plasma levels of alpha-TOH. The aim of this study was to investigate the putative impact of alpha-TTP knock-out on glucose metabolism in mice. Mice deficient for alpha-TTP and wild-type control littermates were fed a diet containing 200 mg alpha-tocopheryl acetate per kg to ameliorate alpha-TOH deficiency in knock-out mice. We investigated fasting and postprandial plasma glucose, insulin and triglyceride levels of both groups of mice at different ages. All genotypes and age groups were further subjected to glucose and insulin tolerance tests, and number of insulin-producing islets of Langerhans were determined. Plasma alpha-TOH levels of knock-out mice were 34% the levels of wild-type controls: Any signs of alpha-TOH deficiency were absent at any age. Unexpectedly, serum glucose levels both in the fasted and in the fed state were lower in alpha-TTP-deficient mice at any age. Removal rates for intraperitoneally injected glucose were found to be significantly increased in young alpha-TTP-deficient mice. This improved glucose tolerance was caused by increased insulin secretion in response to an intraperitoneal glucose challenge due to an increased number of pancreatic islets, as well as by increased sensitivity to intraperitoneally injected insulin, both significantly promoting glucose metabolism in alpha-TTP-deficient mice. Our findings suggest that alpha-TTP-deficiency in states of alpha-TOH supplementation unexpectedly promotes glucose tolerance in mice due to both increased insulin secretion and insulin action, suggesting differential roles of alpha-TTP and alpha-TOH in the pathogenesis of type 2 diabetes mellitus.


The relationship between topical anti-glaucoma medications and the development of lacrimal drainage system obstruction.
To evaluate whether any topical anti-glaucoma medications increase the risk of lacrimal drainage system obstruction or whether the presence of preservatives alone is sufficient to generate obstruction. This nested case-control study compared a group of patients with lacrimal duct obstruction who received topical anti-glaucoma medications to a control group of patients without obstruction. The medical records of 255 patients with glaucoma who consulted the Oculoplastic Section with complaints of watery eyes were reviewed. Among these patients, 59 exhibited lacrimal drainage obstruction. Ninety-four percent of patients with lacrimal drainage obstruction used beta-blockers, and 41% used prostaglandin analogs. A logistic regression model was used to adjust for age, sex, and the use of other medications. No significant differences were observed regarding the topical anti-glaucoma medications used between groups. No single topical anti-glaucoma medication demonstrated a stronger association with the development of lacrimal duct obstruction.


Arabidopsis Regenerating Protoplast: A Powerful Model System for Combining the Proteomics of Cell Wall Proteins and the Visualization of Cell Wall Dynamics.
The development of a range of sub-proteomic approaches to the plant cell wall has identified many of the cell wall proteins. However, it remains difficult to elucidate the precise biological role of each protein and the cell wall dynamics driven by their actions. The plant protoplast provides an excellent means not only for characterizing cell wall proteins, but also for visualizing the dynamics of cell wall regeneration, during which cell wall proteins are secreted. It therefore offers a unique opportunity to investigate the de novo construction process of the cell wall. This review deals with sub-proteomic approaches to the plant cell wall through the use of protoplasts, a methodology that will provide the basis for further exploration of cell wall proteins and cell wall dynamics.


What you need to know: detecting alcohol problems in general medical practice.
In the US, about 11% to 20% of patients presenting to general medical clinics are diagnosed as suffering from alcohol abuse or dependence. Alcohol screening in primary care settings, whether in the US or Singapore, can utilise various strategies for the early detection of alcohol problems. This paper briefly reviews several self-reports and screening procedures to assist general practitioners in identifying problem drinkers. The use of CAGE questionnaire, MAST, and its variation, SAAST and the AUDIT, are discussed and evaluated. Likewise, useful biochemical markers of excessive alcohol consumption like the liver enzymes (AST, ALT, GGT), MCV, CDT are described. They can be combined with each other to improve validity or used in conjunction with self-report screening tests for more accurate detection of problem drinkers. In particular, use of the AUDIT for routine screening of alcohol problems in primary care settings is recommended. Selective administration to those with at least two drinks per setting can overcome time constraints. Alternatively, sequential screening utilising the TRAUMA questionnaire with frequency and quantity questions administered to higher frequency drinkers can circumvent concerns about direct questioning. Use of self-reports and when possible, biochemical screening for alcohol problems should be a standard part of primary care practice.


Aromatic C-H Methylation and Other Functionalizations via the Rh(III)-Catalyzed Migratory Insertion of Bis(phenylsulfonyl)carbene and Subsequent Transformations.
The Rh(III)-catalyzed migratory insertion of bis(phenylsulfonyl)carbene into aromatic C-H bonds has been developed. A variety of bis(phenylsulfonyl)methyl derivatives were prepared with good yields under mild conditions. The methylated products were readily obtained after reductive desulfonylation. Furthermore, the diverse transformations of bis(phenylsulfonyl)methyl to trideuteriomethyl, aldehyde, and other functional groups were demonstrated.


Significant variation in the performance of DNA methylation predictors across data preprocessing and normalization strategies.
DNA methylation (DNAm)-based predictors hold great promise to serve as clinical tools for health interventions and disease management. While these algorithms often have high prediction accuracy, the consistency of their performance remains to be determined. We therefore conduct a systematic evaluation across 101 different DNAm data preprocessing and normalization strategies and assess how each analytical strategy affects the consistency of 41 DNAm-based predictors. Our analyses are conducted in a large EPIC DNAm array dataset from the Jackson Heart Study (N = 2053) that included 146 pairs of technical replicate samples. By estimating the average absolute agreement between replicate pairs, we show that 32 out of 41 predictors (78%) demonstrate excellent consistency when appropriate data processing and normalization steps are implemented. Across all pairs of predictors, we find a moderate correlation in performance across analytical strategies (mean rho = 0.40, SD = 0.27), highlighting significant heterogeneity in performance across algorithms. Successful or unsuccessful removal of technical variation furthermore significantly impacts downstream phenotypic association analysis, such as all-cause mortality risk associations. We show that DNAm-based algorithms are sensitive to technical variation. The right choice of data processing strategy is important to achieve reproducible estimates and improve prediction accuracy in downstream phenotypic association analyses. For each of the 41 DNAm predictors, we report its degree of consistency and provide the best performing analytical strategy as a guideline for the research community. As DNAm-based predictors become more and more widely used, our work helps improve their performance and standardize their implementation.


Isolation and characterization of biologically active venom protein from sea snake Enhydrina schistosa.
The present study is designed to investigate the isolation and characterization of biological and biochemical active venom protein from sea snake, Enhydrina schistosa. The highest purification peaks in ion-exchange chromatography on DEAE-cellulose column were obtained for fraction numbers 39-49 when eluted with 0.35-0.45 M NaCl. Eighty per cent purity was obtained in the final stage of purification, and a single protein band of about 44 kDa was visualized in SDS-polyacrylamide gel under reducing condition. Purified venom protein expressed as haemolytic, cytotoxicity and proteolytic activities with lethal concentration (LC50 ) at 2.0 μg/mL. Venom protein exhibits enzymatic activity and hydrolyzed casein and gelatin. Gelatinolytic activity was optimal at pH 5-9. In conclusion, the present results suggested that the sea snake venom might be feasible sources for biologically active substances. Thus, this low molecular weight component of the venom protein could be used in potentially serve biological and pharmaceutical aspects.


Mental health measurement among women veterans receiving co-located, collaborative care services.
Routine use of measurement to identify patient concerns and track treatment progress is critical to high quality patient care. This is particularly relevant to the Primary Care Behavioral Health model, where rapid symptom assessment and effective referral management are critical to sustaining population-based care. However, research suggests that women who receive treatment in co-located collaborative care settings utilizing the PCBH model are less likely to be assessed with standard measures than men in these settings. The current study utilized regional retrospective data obtained from the Veterans Health Administration's electronic medical record system to: (1) explore rates of mental health measurement for women receiving co-located collaborative care services (N = 1008); and (2) to identify predictors of mental health measurement in women veterans in these settings. Overall, only 8% of women had documentation of standard mental health measures. Measurement was predicted by diagnosis, facility size, length of care episode and care setting. Specifically, women diagnosed with depression were less likely than those with anxiety disorders to have standard mental health measurement documented. Several suggestions are offered to increase the quality of mental health care for women through regular use of measurement in integrated care settings.


Post-spinal hypotension at cesarean section: the denial of evidence.
Post-spinal hypotension at cesarean section appears difficult to prevent, despite the three obligatory so-called preventative measures. So far, literature data provide no compelling evidence that expectations have been met in this regard. A critical appraisal of volume preload, ephedrine prophylaxis and left lateral supine position shows that the preventative measures should be re-evaluated. New avenues should be explored aiming at a better prevention and decrease in both the prevalence and magnitude of post-spinal hypotension at cesarean section.


Exploring change in a group-based psychological intervention for multiple sclerosis patients.
The study is focused on a group-based cognitive behavioral intervention aimed at promoting the quality of life and psychological well-being of multiple sclerosis patients. The study investigates how the group intervention promoted change among participants and fostered their adjustment to the illness. The intervention involved six groups of patients (a total of 41 patients) and included four consecutive sessions and a 6-month follow-up. To explore change, verbatim transcripts of the intervention sessions were analyzed using a mixed-methods content analysis with qualitative data combined with descriptive statistics. The categories of resistance and openness to change were used to describe the process of change. Resistance and openness to change coexisted during the intervention. Only in the first session did resistance prevail over openness to change; thereafter, openness to change gradually increased and stabilized over time, and openness to change was then always stronger than resistance. The study builds on previous research on the effectiveness of group-based psychological interventions for multiple sclerosis patients and gives methodological and clinical suggestions to health care professionals working with multiple sclerosis patients. Implications for rehabilitation The study suggests that a group-based cognitive behavioral intervention for multiple sclerosis patients focused on the promotion of identity redefinition, a sense of coherence and self-efficacy in dealing with multiple sclerosis fosters the process of change and may be effective in promoting patients' adjustment to their illness. Health care professionals leading group-based psychological interventions for multiple sclerosis patients should be aware that resistance and openness to change coexist in the process of change. The study suggests that the duration of the intervention is a crucial factor: a minimum of three sessions appears to be necessary for group participants to develop greater openness to change and follow-up sessions should be implemented to maintain positive changes among participants. The use of qualitative instruments to evaluate group interventions captures the complexity of processes and gives useful indications to health professionals to improve rehabilitation programs.


Distinguishing the Effects of Stress Intensity and Stress Duration in Plant Responses to Salinity.
Species-specific variation in response to stress is a key driver of ecological patterns. As climate change alters stress regimes, coastal plants are experiencing intensifying salinity stress due to sea-level rise and more intense storms. This study investigates the variation in species' responses to presses and pulses of salinity stress in five glycophytic and five halophytic species to determine whether salinity intensity, duration, or their interaction best explain patterns of survival and performance. In salinity stress exposure experiments, we manipulated the intensity and duration of salinity exposure to challenge species' expected salinity tolerances. Salinity intensity best explained patterns of survival in glycophytic species, while the interaction between intensity and duration was a better predictor of survival in halophytic species. The interaction between intensity and duration also best explained biomass and chlorophyll production for all tested species. There was interspecific variability in the magnitude of the interactive effect of salinity intensity and duration, with some glycophytic species (Persicaria maculosa, Sorghum bicolor, and Glycine max) having a more pronounced, negative biomass response. For the majority of species, prolonged stress duration exacerbated the negative effect of salinity intensity on biomass. We also observed an unexpected, compensatory response in chlorophyll production in two species, Phragmites australis and Kosteletzkya virginica, for which the effect of salinity intensity on chlorophyll became more positive with increasing duration. We found the regression coefficient of salinity intensity versus biomass at the highest stress duration, i.e., as a press stressor, to be a useful indicator of salinity tolerance, for which species' salinity-tolerance levels matched those in the literature. In conclusion, by measuring species-specific responses to stress exposure, we were able to visualize the independent and interactive effects of two components of a salinity stress regime, intensity, and duration, to reveal how species' responses vary in magnitude and by tolerance class.


Surgical techniques for repair of primary retinal detachment: Part II. Comparison of present techniques in relation to morbidity.
To compare present surgical techniques for repair of primary retinal detachment. AIM of each technique is closing the retinal break(s), but the approach is either extraocular (e.o.) with scleral buckling or intraocular (i.o.) with pneumatic retinopexy or vitrectomy. The results are similar ranging between 94% and 99% attachment, however, the difference lies in their morbidity and socioeconomic implications which will be compared. Literature of cerclage, minimal segmental buckling, pneumatic retinopexy and primary vitrectomy are reviewed for anatomical results, postoperative PVR, new breaks, reoperation and secondary complications jeopardizing regained visual acuity. All 4 surgical approaches for repair of a primary retinal detachment, i.e., e.o. or i.o. procedures, have one common premise for sustained success: To find and close the break(s). This is so whether the surgery is limited to the break or extending over the entire detachment or whether it is performed as an e.o. or i.o. procedure. At present the i.o. procedures still harbour a 6-fold higher risk of postoperative PVR and 2.5-fold of reoperation. The recent SPR Study confirms that in a phakic eye postoperative visual function is statistically significant better after scleral buckling than after primary vitrectomy. Since the results after the 4 major techniques for reattaching the retina are similar, therefore, the selected procedure has to fulfill 4 postulates: (1) Retinal attachment with 1 operation, (2) it should harbour a minimum of morbidity, (3) be performed on a small budget and under local anesthesia, (4) it should provide long-term visual function, not jeopardized by secondary complications.


Synchronization of chaotic semiconductor laser systems: a vectorial coupling-dependent scenario.
We demonstrate the influence of vectorial coupling on the synchronization behavior of complex systems. We study two semiconductor lasers subject to delayed optical feedback which are unidirectionally coherently coupled via their optical fields. Our experimental and numerical results demonstrate a characteristic synchronization scenario in dependence on the relative feedback phase leading cyclically from chaos synchronization to almost uncorrelated states, and back to chaos synchronization. Finally, we reveal the influence of the feedback phase on the dynamics of the solitary delay system.


Ovarian carcinoma in a 14-year-old with classical salt-wasting congenital adrenal hyperplasia and bilateral adrenalectomy.
A 14-year-old female with classical congenital adrenal hyperplasia because of 21-hydroxylase deficiency underwent bilateral adrenalectomy at 6 years of age as a result of poor hormonal control. Because the patient was adrenalectomized, extra adrenal androgen production was suspected. Imaging studies including pelvic ultrasound and pelvic magnetic resonance imaging (MRI) were obtained to evaluate for adrenal rest tumors of the ovaries. Abdominal MRI was obtained to evaluate for residual adrenal tissue. A cystic lesion arising from her right ovary suspicious for ovarian neoplasm was noted on pelvic MRI. Right salpingo-oophorectomy was performed and histopathological examination revealed ovarian serous adenocarcinoma, low-grade, and well-differentiated. Tumor marker CA-125 was elevated and additional ovarian cancer staging workup confirmed stage IIIC due to one lymph node positive for carcinoma. The patient then developed a large left ovarian cyst, which led to a complete total abdominal hysterectomy and removal of the left ovary and fallopian tube. Pathology confirmed ovarian serous adenocarcinoma with microscopic focus of carcinoma in the left ovary. After numerous complications, the patient responded well to chemotherapy, CA-125 levels fell and no evidence of carcinoma was observed on subsequent imaging. To our knowledge, this is the first reported case of an ovarian serous adenocarcinoma in a patient with CAH. Although rare, we propose that the ovaries were the origin of androgen production and not residual adrenal tissue. The relationship between CAH and ovarian carcinomas has yet to be established, but further evaluation is needed given the poor survival rate of high-grade serous ovarian carcinoma.


Muscle-tendon unit stiffness does not independently affect voluntary explosive force production or muscle intrinsic contractile properties.
This study examined the relationship of muscle-tendon unit (MTU) stiffness and explosive force production during voluntary and evoked contractions of the knee extensors. Thirty-four untrained participants performed a series of explosive voluntary and electrically evoked (octets (8 pulses, 300 Hz) via femoral nerve stimulation) isometric contractions. Maximum voluntary force (MVF) was assessed during maximum voluntary contractions. Explosive force production was assessed as the time taken, from force onset (0 N), to achieve specific levels of absolute (25-300 N) and relative force (5%-75% MVF) during the explosive contractions. Ultrasonic images of the vastus lateralis were recorded during 10-s ramp contractions to assess MTU stiffness, which was expressed in absolute (N · mm(-1)) and relative (to MVF and resting tendon-aponeurosis length) terms. Bivariate correlations suggested that absolute MTU stiffness was associated with voluntary explosive force (time to achieve 150-300 N: r = -0.35 to -0.54, P < 0.05). However, no relationships between stiffness and voluntary explosive force were observed when the influence of MVF was removed, either via partial correlations of absolute values (P ≥ 0.49) or considering relative values (P ≥ 0.14). Similarly, absolute MTU stiffness was related to explosive force during evoked octet contractions (r = -0.41 to -0.64, P < 0.05), but these correlations were no longer present when accounting for the influence of MVF (P ≥ 0.15). Therefore, once maximum strength was considered, MTU stiffness had no independent relationship with voluntary explosive force production or the evoked capacity for explosive force.


Relationship between genotype, assessed by HLA typing, and phenotypic expression of iron status markers in families of 29 probands with hereditary haemochromatosis.
The purpose of this pedigree study, comprising 29 families with hereditary haemochromatosis (HH), was to evaluate the relationship between the genotype (G), based on HLA typing, and the phenotype, based on measurement of iron status markers (serum transferrin saturation and serum ferritin). Due to tight linkage between the HH locus and the HLA-A locus, 172 relatives of the 29 unrelated probands could be assigned into three groups: G0 who were considered to be normal (n = 53), G1 who were considered to be heterozygotes (n = 105), and G2 who were considered to be homozygotes (n = 14), according to whether they had no, one or two HLA haplotypes in common with the proband. A high serum transferrin saturation (> 60%) was present in 8/14 = 57.1% of the homozygotes, in 11/105 = 10.5% of the heterozygotes, and in 0/53 = 0% of the normals. Of the homozygotes, 8/14 = 57.1% had preclinical disease, 4/14 = 28.6% had clinically overt iron overload, while 2/14 = 14.3% had normal iron status markers. None of the heterozygotes had clinical evidence of iron overload. Analysis of HLA alleles and iron status markers suggested that 11/105 = 10.5% subjects initially classified as heterozygotes (G1) according to HLA typing should be reclassified as homozygotes because of abnormal iron status markers, explained by either: homozygous x heterozygous (n = 7) or heterozygous x heterozygous (n = 2) matings, HLA recombination (n = 1) or strongly abnormal iron status markers (n = 1).(ABSTRACT TRUNCATED AT 250 WORDS)


Presentation of Hodgkin's disease as an endobronchial lesion.
Presentation of Hodgkin's disease as an endobronchial lesion is rare. Four such cases are described and nine other previously reported cases are reviewed. The difficulties in diagnosis and management, when the disease presents in this manner, are discussed. This diagnosis must be considered when patients present with an endobronchial tumor because careful staging and treatment may lead to cure with the avoidance of major surgery.


Influence of Software Tool and Methodological Aspects of Total Metabolic Tumor Volume Calculation on Baseline [18F]FDG PET to Predict Survival in Hodgkin Lymphoma.
To investigate the respective influence of software tool and total metabolic tumor volume (TMTV0) calculation method on prognostic stratification of baseline 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography ([18F]FDG-PET) in newly diagnosed Hodgkin lymphoma (HL). 59 patients with newly diagnosed HL were retrospectively included. [18F]FDG-PET was performed before any treatment. Four sets of TMTV0 were calculated with Beth Israel (BI) software: based on an absolute threshold selecting voxel with standardized uptake value (SUV) >2.5 (TMTV02.5), applying a per-lesion threshold of 41% of the SUV max (TMTV041) and using a per-patient adapted threshold based on SUV max of the liver (>125% and >140% of SUV max of the liver background; TMTV0125 and TMTV0140). TMTV041 was also determined with commercial software for comparison of software tools. ROC curves were used to determine the optimal threshold for each TMTV0 to predict treatment failure. Median follow-up was 39 months. There was an excellent correlation between TMTV041 determined with BI and with the commercial software (r = 0.96, p<0.0001). The median TMTV0 value for TMTV041, TMTV02.5, TMTV0125 and TMTV0140 were respectively 160 (used as reference), 210 ([28;154] p = 0.005), 183 ([-4;114] p = 0.06) and 143 ml ([-58;64] p = 0.9). The respective optimal TMTV0 threshold and area under curve (AUC) for prediction of progression free survival (PFS) were respectively: 313 ml and 0.70, 432 ml and 0.68, 450 ml and 0.68, 330 ml and 0.68. There was no significant difference between ROC curves. High TMTV0 value was predictive of poor PFS in all methodologies: 4-years PFS was 83% vs 42% (p = 0.006) for TMTV02.5, 83% vs 41% (p = 0.003) for TMTV041, 85% vs 40% (p<0.001) for TMTV0125 and 83% vs 42% (p = 0.004) for TMTV0140. In newly diagnosed HL, baseline metabolic tumor volume values were significantly influenced by the choice of the method used for determination of volume. However, no significant differences were found in term of prognosis.


Fabrication, characterization and simulation of Ω-gate twin poly-Si FinFET nonvolatile memory.
This study proposed the twin poly-Si fin field-effect transistor (FinFET) nonvolatile memory with a structure that is composed of Ω-gate nanowires (NWs). Experimental results show that the NW device has superior memory characteristics because its Ω-gate structure provides a large memory window and high program/erase efficiency. With respect to endurance and retention, the memory window can be maintained at 3.5 V after 104 program and erase cycles, and after 10 years, the charge is 47.7% of its initial value. This investigation explores its feasibility in the future active matrix liquid crystal display system-on-panel and three-dimensional stacked flash memory applications.


Osteoporosis: A Review of Treatment Options.
Approximately 10 million men and women in the U.S. have osteoporosis,1 a metabolic bone disease characterized by low bone density and deterioration of bone architecture that increase the risk of fractures.2 Osteoporosis-related fractures can increase pain, disability, nursing home placement, total health care costs, and mortality.3 The diagnosis of osteoporosis is primarily determined by measuring bone mineral density (BMD) using noninvasive dual-energy x-ray absorptiometry. Osteoporosis medications include bisphosphonates, receptor activator of nuclear factor kappa-B ligand inhibitors, estrogen agonists/antagonists, parathyroid hormone analogues, and calcitonin.3-6 Emerging therapies utilizing novel mechanisms include a cathepsin K inhibitor and a monoclonal antibody against sclerostin.7,8 While professional organizations have compiled recommendations for the management of osteoporosis in various populations, a consensus has yet to develop as to which is the gold standard; therefore, economic evaluations have been increasingly important to help guide decision-makers. A review of cost-effectiveness literature on the efficacy of oral bisphosphonates has shown alendronate and risedronate to be most cost-effective in women with low BMD without previous fractures.9 Guidelines are inconsistent as to the place in therapy of denosumab (Prolia, Amgen). In economic analyses evaluating treatment of postmenopausal women, denosumab outperformed risedronate and ibandronate; its efficacy was comparable to generic alendronate, but it cost more.10 With regard to older men with osteoporosis, denosumab was also found to be cost-effective when compared with bisphosphonates and teriparatide (Forteo, Lilly).11.


Electroconvulsive therapy: Promoting awareness among primary care physicians.
This article aims to promote awareness among primary care providers and support electroconvulsive therapy as a generally well-tolerated, effective therapeutic modality to treat specific psychiatric conditions in appropriately selected patients. There seem to be several potential barriers to treatment with electroconvulsive therapy including stigma, lack of providers who preform it, and lack of awareness among providers referring patients who may be appropriate candidates. The article provides a brief overview of electroconvulsive therapy principles and topics and includes a case report to illustrate clinical utility. The article proposes the concept that a potential way to overcome barriers to treatment with electroconvulsive therapy may be to promote education and awareness of it as a viable treatment modality among primary care providers.


Culture of human fetal ovarian epithelium in a chemically-defined, serum-free medium: a model for ovarian carcinogenesis.
We report on of the possibility to culture normal human fetal ovarian epithelium in vitro under chemically defined conditions. Cell growth was dependent upon the presence of epidermal growth factor, insulin, and hydrocortisone in the culture medium but was unaffected by the presence of estrogen, progesterone, follicle stimulating hormone, or Müllerian inhibiting Substance. Growth could be maintained for up to 6 passages in culture. The possibility of culturing these cells in serum-free medium may represent an attractive model to investigate the biology of normal ovarian epithelium as well as its role in human ovarian tumorigenesis.


Motivation and Eudaimonic Well-Being in Athletes: A Self-Determination Theory Perspective.
Purpose: Drawing from self-determination theory (SDT), the present study examined the relationship between motivation and eudaimonic well-being in the sport context. Method: The association between motivation and eudaimonic well-being was assessed using a latent variable model through Structural Equation Modeling (SEM). Three hundred ninety-nine athletes (Mage = 25.08, SD = 7.35) from 15 different individual and team sports completed a questionnaire package. Results: Results indicated that integrated and identified regulations positively predicted athletes' eudaimonic well-being. External regulation was also a positive predictor of eudaimonic well-being, while introjected regulation and amotivation negatively predicted athletes' eudaimonic well-being. Finally, athletes' intrinsic motivation did not significantly predict their eudaimonic well-being. Conclusions: Results highlight the complex link between different types of sport motivation and athletes' well-being.