Thermal stability of red algal galactans: Effect of molecular structure and counterions.
Thermal degradation of κ-, ι-, λ-carrageenans, furcellaran, funoran and agarose samples in dry and sol states was investigated. The polysaccharides subjected to heat treatment were characterized by 1H NMR, 13C NMR and FTIR spectroscopy, size exclusion chromatography and static rheometry methods. The microstructure of galactan gels was studied using a cryofixation method in combination with freeze-drying and SEM techniques. Thermal stability at high temperatures decreases in the order of agarose>furcellaran>funoran>κ-carrageenan>λ-carrageenan>ι-carrageenan for dry preparations. The respective sequence for sol state is ι-carrageenan>λ-carrageenan>κ-carrageenan>furcellaran>funoran>agarose. The presence of methoxy groups stabilizes algal polysaccharides whereas divalent cations as counterions increase the susceptibility towards thermal degradation. In dry state the thermal treatment leads to significant desulfation of the galactan before the complete depolymerization occurs. Depending on the sulfation degree and the presence of 3,6-anhydrogalactose residues in the galactan, a notable amount of 5-hydroxymethylfurfural (yield 0.7-21.8%) is formed during the decomposition in sol state.


Bacterial evasion of host immune defense: Yersinia enterocolitica encodes a suppressor for tumor necrosis factor alpha expression.
The ability of the enteropathogenic Yersinia enterocolitica to survive and proliferate in host tissue depends on a 70-kb plasmid known to encode a number of released Yersinia outer proteins that act as virulence factors by inducing cytotoxicity and inhibiting phagocytosis. This study demonstrates that one of the Yersinia outer proteins, the 41-kDa YopB, suppresses the production of tumor necrosis factor alpha (TNF-alpha), a macrophage-derived cytokine with central roles in the regulation of immune and inflammatory responses to infection. This conclusion is based on several lines of evidence. First, in macrophage cultures, suppression of TNF-alpha mRNA expression was induced by culture supernatant (CS+) of plasmid-bearing yersiniae, the effect which was blocked by anti-YopB antiserum. Second, suppression of TNF-alpha production, but not of interleukin-1 (IL-1) and IL-6, was induced by purified YopB. Third, in Yersinia-infected mice, no increase in TNF-alpha mRNA expression was observed in Peyer's patches, the primary site of bacterial invasion, compared with IL-1 (alpha and beta) mRNA. Finally, administration of anti-YopB antiserum to mice prior to infection with Y. enterocolitica increased TNF activity levels in Peyer's patches and coincided with a reduction in bacterial growth. The results thus provide direct evidence for a secreted eubacterial virulence factor that mediates selective suppression of TNF-alpha production. Although suppression of this single cytokine response is probably not sufficient to facilitate survival of the infecting organisms, the results suggest that suppression of TNF-alpha production by YopB significantly contributes to the evasion of Y. enterocolitica from antibacterial host defense.


Precocious obesity predisposes the development of more severe cisplatin-induced acute kidney injury in young adult mice.
Obesity and its consequences can damage the kidney over time. However, less is known about the impact of developing overweight/obesity during childhood on the kidney in adulthood and the renal impact of a superimposed acute kidney injury (AKI). This study evaluated the effect of obesity induced by a high-fat diet initiated soon after weaning on the adult life of mice and their response to superimposed nephrotoxic effects of cisplatin. C57BL/6 post-weaning mice (3 weeks old) were divided into a control group (CT, n = 12) and a high-fat diet group (HF, n = 12). After 9 weeks, animals were further divided into the following groups: CT, CT treated with a single dose of cisplatin (CTCis, 20 mg/kg, i.p.), HF and HF treated with cisplatin (HFCis). The HF group exhibited higher body weight gain compatible with a moderate obesity. Obese mice presented increased visceral adiposity, hyperkalemia, sodium retention, glomerular hyperfiltration and proteinuria, without any significant changes in blood pressure and glycemia. AKI induced by cisplatin was exacerbated in obese animals with a 92% reduction in the GFR versus a 31% decrease in the CTCis group; this sharp decline resulted in severely elevated serum creatinine and urea levels. Acute tubular necrosis induced by cisplatin was worsened in obese mice. The HFCis group exhibited robust systemic and intrarenal inflammation that was significantly higher than that in the CTCis group; the HFCis group also showed a higher degree of renal oxidative stress. In conclusion, the moderate degree of obesity induced shortly after weaning resulted in mild early renal alterations, however, obese young animals were prone to develop a much more severe AKI induced by cisplatin.


Rare Case of Diffuse Large B-Cell Lymphoma Mimicking Acute Monocytic Leukemia, Associated with Complex Karyotype.
Diffuse Large B-Cell Lymphoma (DLBCL), NOS, constitutes 25-35% of adult non-Hodgkin lymphomas in developed countries, and a higher percentage in developing countries; older people are prone to the disease. Three frequent morphological variants have been recognized, including centroblastic, immunoblastic, and anaplastic variants. However, there are still other rare morphological variants of DLBCL, presenting challenge in diagnosis and treatment. A 62-year-old woman sought medical attention with a previous 6-month history of intermittent fever and leukocytosis. Bone marrow (BM) aspiration presented AML with acute monocytic leukemia-like morphologic features. The results of the immunophenotypic analysis suggested mature B cell lymphoma without obvious subtype characteristics. Lymph node biopsy indicated DLBCL of non-germinal centre B-cell subtype (n-GCB). Cytogenetic analysis of the BM cells revealed a 46,XX, trp(1)(q21q32),del(7)(q32q36),t(9;14)(p13;q32) [4]/46,XX [16] karyotype. The patient was diagnosed with EBV-positive DLBCL, NOS based on the combination of lymph node biopsy, clinical, cytological, immunophenotypic, and cytogenetic analyses. To date, no case reports of a patient diagnosed with DLBCL mimicking acute monocytic leukemia with complex karyotype have been reported. We present the case given its rarity, easy misdiagnosis, and poor prognosis. The case highlights the importance of awareness about the rare morphological variant to laboratory staff and hematologists.


Clinical trials in the non-Hodgkin's lymphomata at Stanford University experimental design and preliminary results.
Preliminary results of controlled clinical trials in 127 patients with non-Hodgkin's lymphomata are reported. The rationale for identifying 7 study groups is presented. Treatment programmes which are being studied vary from involved field irradiation to the most aggressive treatment tolerable. The early results suggest that patients with both favourable and unfavourable histologies but of limited extent can be controlled with irradiation. Patients with advanced disease but with favourable histological subgroups are doing as well with a conservative drug programme as with 2 aggressive treatment regimens. These controlled studies and those of others, facilitated by the use of the Rappaport classification and laparotomy staging, give promise of clarifying and improving the management of patients with these lymphomata.


CaMKII activation and dynamics are independent of the holoenzyme structure: an infinite subunit holoenzyme approximation.
The combinatorial explosion produced by the multi-state, multi-subunit character of CaMKII has made analysis and modeling of this key signaling protein a significant challenge. Using rule-based and particle-based approaches, we construct exact models of CaMKII holoenzyme dynamics and study these models as a function of the number of subunits per holoenzyme, N. Without phosphatases the dynamics of activation are independent of the holoenzyme structure unless phosphorylation significantly alters the kinase activity of a subunit. With phosphatases the model is independent of holoenzyme size for N > 6. We introduce an infinite subunit holoenzyme approximation (ISHA), which simplifies the modeling by eliminating the combinatorial complexities encountered in any finite holoenzyme model. The ISHA is an excellent approximation to the full system over a broad range of physiologically relevant parameters. Finally, we demonstrate that the ISHA reproduces the behavior of exact models during synaptic plasticity protocols, which justifies its use as a module in large models of synaptic plasticity.


NIR Laser Responsive Nanoparticles for Ovarian Cancer Targeted Combination Therapy with Dual-Modal Imaging Guidance.
Multifunctional nanoparticles with targeted therapeutic function and diagnostic-imaging are of great interest in the domain of precision therapy. NIR laser responsive nanoparticles (PLGA-PEG-FA encapsulating Bi2S3, PFP, and Dox (designed as FBPD NPs)) are synthesized for ovarian cancer targeted combination therapy with CT/PA dual-modal imaging guidance (PA: photoacoustic; CT: X-ray computed tomography). The FBPD NPS prepared by the double emulsification method revealed excellent dispersity, great stability, outstanding optical properties. The temperature of FBPD NPs increased rapidly after laser irradiation, inducing liquid-to-gas conversion of perfluoropentane (PFP), and promoting the release of Dox up to 86.7%. These FBPD NPs demonstrated their outstanding imaging capability for both PA and CT imaging both in vitro and in vivo, providing the potential for therapeutic guidance and monitoring. Assisted by folic acid, these nanoparticles could highly enrich in ovarian tumor tissue and the accumulation peaked at 3 h after intravenous administration. The desirable photothermal-conversion efficiency of the nanoparticles combined with chemotherapy achieved highly efficient therapy, which was demonstrated both in vitro and in vivo. We successfully constructed multifunctional theranostic FBPD NPs for highly efficient PTT/chemotherapy combined therapy with dual CT/PA imaging guidance/monitoring. The unique nanoparticles with multiple abilities pave an emerging way toward precise treatment of ovarian cancer.


Japanese cohort mortality from cancers of the upper digestive and respiratory tracts.
Cohort mortality between 1875 and 1975 in Japan from cancers of the oesophagus, tongue, and larynx were examined. Death rates were compared with per capita alcohol and tobacco use which are major aetiological agents for these tumours in Westernized countries. Cohort mortality from cancer of the oesophagus remains high for both sexes in a country with historically low alcohol consumption. More consistent with this low drinking pattern are the rates for cancers of the tongue which remain among the lowest in the world. Cancers of the larynx, which have been associated with tobacco and alcohol, declined among successive cohorts, which was in contrast to the sharp cohort increases for lung cancers and tobacco use in Japan during the same period.


The prevalence of thyroid dysfunction in Jordan: a national population-based survey.
The objectives of this study are to assess the prevalence of clinical and subclinical hypo- and hyperthyroidism and their associated factors among Jordanian adults. In a cross-sectional population-based survey, a representative sample that included 3753 Jordanian adults was selected from the 12 governorates that represent the three regions of the country, in the year 2017. Sociodemographic and clinical data were obtained and blood samples were collected from all participants. Thyroid stimulating hormone (TSH), free tri-iodothyronine (FT3), free thyroxine (FT4), thyroglobulin antibody (TgAb) and thyroid peroxidase antibody (TPOAb) were measured to evaluate the thyroid function. The overall prevalence of thyroid dysfunction was 11.9%. Around 76% of patients with thyroid dysfunction were previously undiagnosed. The prevalence of hypothyroidism and subclinical hypothyroidism was 3.1 and 5.3%, respectively. The prevalence of hyperthyroidism and subclinical hyperthyroidism was 1.0 and 2.5%, respectively. Female preponderance which was mainly related to hypothyroid disorders was evident. The prevalence of positive TPOAb and TgAb in the study population was 14.9 and 15.3%, respectively. The prevalence of detectable TPOAb and TgAb in the euthyroid participants was10.3 and 11.9%, respectively. Logistic regression analysis revealed that female sex, age ≥ 50 years and the presence of TgAb and TPOAb were strongly associated with hypothyroidism. Hyperthyroidism was significantly associated with the presence of TPOAb and age ≥ 50 years. The prevalence of unrecognized thyroid dysfunction is high among Jordanians. A public health policy of screening high risk groups particularly those ≥50 years of age is recommended.


Perspectives of student incivility in the online learning environment and social media platforms.
The purpose of this study was to examine student and faculty perspectives of student incivility in the online learning environment and social media platforms and to describe the participants' recommendations for promoting civility. Mixed-method design was used to collect data from a convenience sample of students and faculty in a nursing program in the Southeast United States. 53 faculty members and 203 nursing students participated, and the majority agreed that incivility is a problem to some degree. Several themes emerged for effectively promoting civility. Incivility is a problem, but students and faculty believe the use of proactive strategies may be effective in promoting civility. Implications for International Audience: As more nursing programs move to the OLE, even if temporarily as occurred during the pandemic, coupled with the increase in social media use, there is need to recognize and implement strategies to thwart the incidence of incivility.


Exploring Partonic Structure of Hadrons Using ab initio Lattice QCD Calculations.
Following our previous proposal, we construct a class of good "lattice cross sections" (LCSs), from which we can study the partonic structure of hadrons from ab initio lattice QCD calculations. These good LCSs, on the one hand, can be calculated directly in lattice QCD, and on the other hand, can be factorized into parton distribution functions (PDFs) with calculable coefficients, in the same way as QCD factorization for factorizable hadronic cross sections. PDFs could be extracted from QCD global analysis of the lattice QCD generated data of LCSs. We also show that the proposed functions for lattice QCD calculation of PDFs in the literature are special cases of these good LCSs.


[Preparation and performance of Chitosan-oligosaccharides/DNA complex nanoparticles].
Comparing to Chitosan, Chitosan-oligosaccharides have several special functions, such as water-soluble, antitumor activity, immunostimulating effects, and antimicrobial activity. The chitosan-oligosaccharide, the molecular weight of which was about 5000, was used as research model. According to the agarose gel electrophoresis and UV spectrophotometer it was proved that electrostatic interaction was playing a very important role in the formation process of chitosan-oligosaccharide/DNA complex. The potential of adsorbing DNA on chitosan-oligosaccharide was analyzed by gel electrophoresis and UV spectrophotometer, and it was indicated that chitosan-oligosaccharide can improve the storage and structure stability of DNA. To check its protection ability to DNA by DNase I digestive experiment, the result showed that chitosan-oligosaccharide could load with plasmid effectively and protect DNA from being digested by DNase I. It was proved that chitosan-oligosacchide was safe and effective for gene delivery and will have a very good future in the field of gene therapy.


Protein kinase C in the regulation of smooth muscle contraction.
The cellular and molecular mechanisms underlying smooth muscle contraction are reviewed in the light of recent studies of smooth muscle ultrastructure and of the role of polyphosphoinositide turnover and protein kinase C function in smooth muscle contraction. A new model of smooth muscle contraction is proposed that differs radically from accepted views, particularly the latch bridge hypothesis, in terms of both Ca2+ messenger function and the molecular events underlying this process. A coordinate fibrillar domain model of contraction is proposed in which the initial and sustained phases of contraction are mediated by different cellular and molecular events. The initial phase of response is mediated by a rise in [Ca2+]c and the resulting calmodulin-dependent activation of both myosin light chain kinase and the dissociation of caldesmon from the actin-caldesmon-tropomyosin-myosin fibrillar domain. These events lead to an interaction between actin and the phosphorylated light chains of myosin just as in previous models. However, this initial phase is followed by a sustained phase in which a rise in [Ca2+]sm stimulates the plasma membrane-associated, Ca2+-sensitive form of protein kinase C that results in the phosphorylation of both structural and regulatory components of the filamin-actin-desmin fibrillar domain. These events underlie the tonic phase of contraction.


Validation and maintaining laboratory developed molecular tests compliant with ISO15189 for diagnosis of intestinal parasitic infections.
Although, in the past few decades molecular diagnostics of parasitic infections have been accepted as first-line diagnostics, laboratories tend to be reluctant of introducing nucleic acid based tests as they dread the validation of laboratory developed tests (LDTs) compliant with ISO1589. This paper describes how to set tailor-made performance characteristics for the validation of laboratory developed tests (LDTs) for the molecular diagnosis of intestinal parasitic infections complying with the ISO 15189 guidelines. Then, just as important, maintaining these tests by daily monitoring, external quality assessment schemes, and reassessment of the test set-up. Tailoring performance characteristics for the validation of LDTs defining criteria that make sense and actually leading to a process of continuous quality improvement in the day-to-day practice of a diagnostic laboratory. It is essential or even obligatory to modify these characteristics, skip, or to add additional characteristics based on personal or changing insights fitted for a specific setting.


In vivo construction of a hybrid pathway for metabolism of 4-nitrotoluene in Pseudomonas fluorescens.
Pseudomonas fluorescens 410PR grows on 4-nitrobenzoate but does not metabolize 4-nitrotoluene. The TOL pWW0 delta pm plasmid converts 4-nitrotoluene into 4-nitrobenzoate through its upper pathway, but it does not metabolize 4-nitrobenzoate. P. fluorescens 410PR(pWW0 delta pm) transconjugants were isolated and found to be able to grow on 4-nitrotoluene. This phenotype was stable after growth for at least 300 generations without any selective pressure. P. fluorescens 410PR(pWW0 delta pm) converted 4-nitrotoluene into 4-nitrobenzoate via 4-nitrobenzylalcohol and 4-nitrobenzaldehyde. 4-Nitrobenzoate was metabolized via 4-hydroxylaminobenzoate and finally yielded NH4+ and 3,4-dihydroxybenzoate, which was mineralized.


Partial pathogen protection by tick-bite sensitization and epitope recognition in peptide-immunized HLA DR3 transgenic mice.
Ticks are notorious vectors of disease for humans, and many species of ticks transmit multiple pathogens, sometimes in the same tick bite. Accordingly, a broad-spectrum vaccine that targets vector ticks and pathogen transmission at the tick/host interface, rather than multiple vaccines against every possible tickborne pathogen, could become an important tool for resolving an emerging public health crisis. The concept for such a tick protective vaccine comes from observations of an acquired tick resistance (ATR) that can develop in non-natural hosts of ticks following sensitization to tick salivary components. Mice are commonly used as models to study immune responses to human pathogens but normal mice are natural hosts for many species of ticks and fail to develop ATR. We evaluated HLA DR3 transgenic (tg) "humanized" mice as a potential model of ATR and assessed the possibility of using this animal model for tick protective vaccine discovery studies. Serial tick infestations with pathogen-free Ixodes scapularis ticks were used to tick-bite sensitize HLA DR3 tg mice. Sensitization resulted in a cytokine skew favoring a Th2 bias as well as partial (57%) protection to infection with Lyme disease spirochetes (Borrelia burgdorferi) following infected tick challenge when compared to tick naïve counterparts. I. scapularis salivary gland homogenate (SGH) and a group of immunoinformatic-predicted T cell epitopes identified from the I. scapularis salivary transcriptome were used separately to vaccinate HLA DR3 tg mice, and these mice also were assessed for both pathogen protection and epitope recognition. Reduced pathogen transmission along with a Th2 skew resulted from SGH vaccination, while no significant protection and a possible T regulatory bias was seen in epitope-vaccinated mice. This study provides the first proof-of-concept for using HLA DR tg "humanized" mice for studying the potential tick protective effects of immunoinformatic- or otherwise-derived tick salivary components as tickborne disease vaccines.


Intraoperative Tumor Detection Using a Ratiometric Activatable Fluorescent Peptide: A First-in-Human Phase 1 Study.
Positive surgical margins remain a significant challenge in breast cancer surgery. This report describes the use of a novel, first-in-human ratiometric activatable cell-penetrating peptide in breast cancer surgery. A two-part, multi-institutional phase 1 trial of AVB-620 with a 3+3 dose escalation and dose-expansion cohorts was conducted. The patients received an infusion of AVB-620 2-20 h before planned lumpectomy/mastectomy and sentinel node biopsy/axillary dissection. Imaging analysis was performed on images obtained from the surgical field as well as post-excision surgical specimens. Pathology reports were obtained to correlate imaging results with histopathologic data. Information on physical adverse events and laboratory abnormalities were recorded. A total of 27 patients received infusion of AVB-620 and underwent surgical excision of breast cancer. The findings showed no adverse events or laboratory values attributable to infusion of AVB-620. The 8-mg dose was selected from the dose-escalation cohort for use with the expansion cohort based on imaging data. Region-of-interest (ROI) imaging analysis from the 8-mg cohort demonstrated measurable changes between pathology confirmed tumor-positive and tumor-negative tissue. Intraoperative imaging of surgical specimens after infusion with AVB-620 allowed for real-time tumor detection. Infusion of AVB-620 is safe and may improve intraoperative detection of malignant tissue during breast cancer operations.


Metal nanoparticles via the atom-economy green approach.
Metal nanoparticles (NPs) of Cu (air-stable), Ag, and Au have been prepared using an atom-economy green approach. Simple mechanical stirring of solid mixtures (no solvent) of a metal salt and ammonia borane at 60 degrees C resulted in the formation of metal NPs. In this reaction, ammonia borane is transformed into a BNH(x) polymer, which protects the NPs formed and halts their growth. This results in the formation of the BNH(x) polymer protected monodisperse NPs. Thus, ammonia borane used in these reactions plays a dual role (reducing agent and precursor for the stabilizing agent).


Prostaglandin E2 synthesis and cyclooxygenase expression in abdominal aortic aneurysms.
The purpose of this study was to evaluate the expression of prostaglandin E2 (PGE2) and the two cyclooxygenase isoforms (cox1 and cox2) in human abdominal aortic aneurysm (AAA) tissue. Ten specimens each of normal aortas and aneurysmal aortas were collected and used for histologic analysis and whole organ culture. An enzyme-linked immunosorbent assay for PGE2 was performed on the media from the aortic explant whole organ culture. An immunohistochemical analysis for PGE2 was performed, as was in situ hybridization for cox1 and cox2 on tissue sections. PGE2 production of AAA specimens was found to be 67,287 +/- 27,303 pg/ml as compared with 1698 +/- 858 pg/ml for normal aortic specimens (p < 0.001). PGE2 was localized by immunohistochemical analysis to the inflammatory infiltrate in AAAs. Minimal expression was noted in normal aortas. Using in situ hybridization, little expression of cox1 was noted in either the normal or the AAA specimens. Cox2 was expressed by macrophage-like cells within the inflammatory infiltrate of the AAA specimens but was not significantly expressed in the normal aorta. The expression of PGE2 is associated with the pathogenesis of human AAAs. Its expression is localized to macrophage-like cells within the inflammatory infiltrate and is controlled by the cox2 isoform of cyclooxygenase. Cox2 is, therefore, a potential target for pharmacotherapy of AAAs.


Level of knowledge about anaphylaxis among health care providers.
Level of knowledge about anaphylaxis was evaluated in health care providers by using a self-administered questionnaire. A total of 1172 participants responded to the survey, and previously half of them had met a case with anaphylaxis with a highest rate in primary and a lowest rate in tertiary care (p= 0.005). 84.7% of participants answered the questions about the symptoms of anaphylaxis correctly. Although 62.6% of the group knew correctly anaphylaxis treatment steps, 44.7% of them agreed to administer epinephrine if they suspected of a subject with anaphylaxis. One third of the group indicated appropriate route of epinephrine administration. 85.2% of participants agreed to refer the patient to allergy clinic despite 33.7% of the group were unaware of where the nearest allergy clinic was. Only 20.3% of the respondents have heard about epinephrine auto-injector. Anaphylaxis was often diagnosed and managed inadequately, regardless of practice location, employment status and speciality in north-eastern Turkey.


Design consideration of an x-ray imaging crystal spectrometer for China Fusion Engineering Test Reactor.
The x-ray imaging crystal spectrometer (XICS) is proposed as the principal method of diagnostics for plasma ion temperature and rotation for the China Fusion Engineering Test Reactor (CFETR) for its simplicity in implementation and no reliance on neutral beams. For D-T experiments with the electron temperature as high as 35-40 keV at the core region, highly charged high-Z ions can serve as the diagnostic ions for the XICS. For the CFETR, Xe44+, Xe51+, and W64+ are selected as the impurity ions. Appropriate crystal parameters are selected, as well as the preliminary layout for the spectrometer. We estimated the general performance of the spectrometer, including the emissivity of the impurities, the spatial resolution of the x-ray detector, and the expected count rate of line emissions. For the application in the fusion reactor environment, the effect of neutron irradiation on the crystal is briefly discussed.


Dewetting and spreading transitions for active matter on random pinning substrates.
We show that sterically interacting self-propelled disks in the presence of random pinning substrates exhibit transitions among a variety of different states. In particular, from a phase separated cluster state, the disks can spread out and homogeneously cover the substrate in what can be viewed as an example of an active matter wetting transition. We map the location of this transition as a function of activity, disk density, and substrate strength, and we also identify other phases including a cluster state, coexistence between a cluster and a labyrinth wetted phase, and a pinned liquid. Convenient measures of these phases include the cluster size, which dips at the wetting-dewetting transition, and the fraction of sixfold coordinated particles, which drops when dewetting occurs.


A case of Yersinia pseudotuberculosis septicemia accompanied by a large abdominal tumor.
A 2-year-old girl with Yersinia pseudotuberculosis septicemia had a large abdominal mass that had to be differentiated from malignant tumor. The mass disappeared rapidly with antibiotic therapy and was defined to be a cluster of enlarged ileocecal lymph nodes by the clinical course and the findings at ultrasonic examination and Gallium scintigraphy.


Quantitation of Trans-Fatty Acids in Children from the National Health and Nutrition Examination Survey.
Trans-fatty acids (TFA) are geometric isomers of naturally occurring cis-fatty acids, formed industrially through partial hydrogenation of vegetable oils or naturally in ruminant animals. TFA intake has been associated with risk factors for cardiovascular disease; therefore, reduced TFA consumption is a major public health objective. Food intake studies have provided estimates for TFA levels in the U.S. and we previously assessed TFA blood concentrations in fasting U.S. adults in the National Health and Nutrition Examination Survey (NHANES), finding an average 54% decrease in TFA between 1999-2000 and 2009-2010. The aim of this study was to determine nationally representative estimates for plasma TFA concentrations in children in the U.S. population. We used the CDC isotope dilution-gas chromatography-negative chemical ionization-mass spectrometry (ID-GC-NCI-MS) method to quantitate four major TFA, palmitelaidic acid, elaidic acid, trans-vaccenic acid, and linoelaidic acid, in a nationally representative group of children in the U.S. population using NHANES samples. TFA were derivatized with pentafluorobenzyl-bromide and analyzed by GC-MS in selected ion monitoring mode using NCI with methane reagent gas. Separation was carried out on a Select FAME 200 m column with hydrogen carrier gas. The TFA limits of detection ranged from 0.02 μM to 0.43 μM. The intraday and inter-day % coefficients of variation ranged from 1-11% CV and 6-15% CV respectively. The mean accuracy for all four TFA was 102% (95% CI: 98%-107%). The TFA were measured in 916 participants (age: 6-19 years) from NHANES 1999-2000 and 1718 participants (age: 3-19 years) from NHANES 2009-2010, and were detected in all samples. Geometric means for the sum of the 4 TFAs were 80.7 μmol/l (95% CI: 74.6-87.3 μmol/L) and 30.6 μmol/l (95% CI: 29.0-32.3 μmol/L) in the NHANES 1999-2000 and 2009-2010, respectively. Overall TFA concentrations were 62% lower in NHANES 2009-2010 compared to 1999-2000. TFA levels in children in the U.S. population are notably lower in NHANES 2009-2010 compared to NHANES 1999-2000 suggesting an overall reduction of TFA levels in children. N/A.


Perspectives of older people about contingency planning for falls in the community: A qualitative meta-synthesis.
Despite consistent evidence for the positive impact of contingency planning for falls in older people, implementation of plans often fail. This is likely due to lack of recognition and knowledge about perspectives of older people about contingency planning. The objective of this research was to explore the perspectives of older people living in the community about use of contingency planning for getting help quickly after a fall. A systematic literature search seeking qualitative research was conducted in April 2014, with no limit placed on date of publication. Medline, EMBASE, Ageline, CINAHL, HealthSource- Nursing/Academic Edition, AMED and Psych INFO databases were searched. Three main concepts were explored and linked using Boolean operators; older people, falls and contingency planning. The search was updated until February 2016 with no new articles found. After removal of duplicates, 562 articles were assessed against inclusion and exclusion criteria resulting in six studies for the meta-synthesis. These studies were critically appraised using the McMaster critical appraisal tool. Bespoke data extraction sheets were developed and a meta-synthesis approach was adopted to extract and synthesise findings. Three themes of 'a mix of attitudes', 'careful deliberations' and 'a source of anxiety' were established. Perspectives of older people were on a continuum between regarding contingency plans as necessary and not necessary. Levels of engagement with the contingency planning process seemed associated with acceptance of their risk of falling and their familiarity with available contingency planning strategies. Avoiding a long lie on the floor following a fall is imperative for older people in the community but there is a lack of knowledge about contingency planning for falls. This meta-synthesis provides new insights into this area of health service delivery and highlights that implementation of plans needs to be directed by the older people rather than the health professionals.


Practical application of the ICRP Human Respiratory Tract Model.
The ICRP Publication 66 Human Respiratory Tract Model (HRTM) has been applied to calculate dose coefficients and bioassay functions using default values of parameters relating to the material and the subjects. The ICRP Task Group on Internal Dosimetry (INDOS) has developed a guidance document on application of the HRTM in situations where using specific information can improve dose assessments. INDOS is now revising the worker exposure documents (ICRP Publications 68 and 78). Application of the HRTM requires a review of the lung-to-blood absorption characteristics of inhaled radionuclides. Where appropriate, compound-specific absorption parameter values will be derived, and other compounds will be assigned to default Types using current information. Although no major changes to the HRTM are envisaged, this revision provides an opportunity for some refining and updating in the light of experience and new information.


Sequential Functionalization of meta-C-H and ipso-C-O Bonds of Phenols.
The use of a template as a linchpin motif in directed remote C-H functionalization is a versatile yet relatively underexplored strategy. We have developed a template-directed approach to realizing one-pot sequential palladium-catalyzed meta-selective C-H olefination of phenols, and nickel-catalyzed ipso-C-O activation and arylation. Thus, this bifunctional template converts phenols to synthetically useful 1,3-disubstituted arenes.


Assessment of marital relationships of hemodialysis patients.
In addition to the somatic problems associated with uremia and dialysis it is apparent that successful hemodialysis is dependent upon psychological adjustment to this type of therapy. While previous studies have focused on the patient or spouse as individuals, patterns of marital interactions and conflicts have not been systematically evaluated. These factors ere examined in 17 medically stable patients maintained on hemodialysis for a mean duration of 22 +/- 4 SE months. Standardized pssychiatric evaluation forms ere used to examine mood and cognition disturbances in all patients and spouses, and a deailed marital questionnaire, which each patient and spouse filled out independently, was used to evaluate fundamental aspects of the marital relationship...


Neural Basis of Intrinsic Motivation: Evidence from Event-Related Potentials.
Human intrinsic motivation is of great importance in human behavior. However, although researchers have focused on this topic for decades, its neural basis was still unclear. The current study employed event-related potentials to investigate the neural disparity between an interesting stop-watch (SW) task and a boring watch-stop task (WS) to understand the neural mechanisms of intrinsic motivation. Our data showed that, in the cue priming stage, the cue of the SW task elicited smaller N2 amplitude than that of the WS task. Furthermore, in the outcome feedback stage, the outcome of the SW task induced smaller FRN amplitude and larger P300 amplitude than that of the WS task. These results suggested that human intrinsic motivation did exist and that it can be detected at the neural level. Furthermore, intrinsic motivation could be quantitatively indexed by the amplitude of ERP components, such as N2, FRN, and P300, in the cue priming stage or feedback stage. Quantitative measurements would also be convenient for intrinsic motivation to be added as a candidate social factor in the construction of a machine learning model.


Effects of short-term infliximab therapy on autoantibodies in systemic lupus erythematosus.
To analyze changes in autoantibodies occurring in patients with systemic lupus erythematosus (SLE) treated with 4 infusions of the chimeric anti-tumor necrosis factor alpha (TNFalpha) antibody infliximab. In an open-label safety study, 7 patients with SLE were treated with infliximab at weeks 0, 2, 6, and 10 in combination with azathioprine or methotrexate. Antibodies to double-stranded DNA (dsDNA) were determined by radioimmunoassay and the Crithidia luciliae indirect immunofluorescence assay; anticardiolipin antibodies (aCL) and antibodies to histone and chromatin were measured by enzyme-linked immunosorbent assay. Antihistone antibodies were also analyzed by immunoblotting. Peripheral blood mononuclear cells from healthy individuals and SLE patients were incubated for 2 weeks with or without TNFalpha. TNFalpha was removed by washing and by the addition of infliximab. Apoptotic cells were stained with annexin V and analyzed by flow cytometry. Autoantibodies to dsDNA increased in 5 of 7 patients. Histone, chromatin, and IgM aCL levels were increased in 4 of 7, 6 of 7, and 4 of 7 patients, respectively, peaking 4-10 weeks after the last infliximab infusion, but falling to baseline levels or lower thereafter. In the in vitro experiments, TNF withdrawal after long-term incubation with recombinant human TNF led to increased percentages of apoptotic cells. While TNF blockade was clinically effective, the majority of SLE patients treated with infliximab showed an increase in autoantibodies to nuclear antigens and phospholipids. These increases were transient and were not associated with disease flares. Increased availability of apoptotic antigens after TNF blockade may play a role in the autoantibody formation induced by TNF blockade.


Orthodontic treatment of unilateral cleft lip and alveolus patient with maxillary lateral incisor missing: case report.
The esthetics of a patient with a cleft lip and alveolus and missing maxillary lateral incisor is important. A girl, aged 9 years 3 months with repaired left unilateral cleft of primary palate only was referred for orthodontic evaluation of her anterior tooth-crowding. She was unhappy with the unattractive appearance of her maxillary anterior teeth, which were behind her mandibular anterior teeth. Alveolar bone grafting along with canine substitution to replace her missing lateral incisor were recommended for this patient. The post-treatment results were excellent with good occlusion, acceptable profile, and remained stable one year after conclusion of active treatment.


ST-Segment Elevation and Fractionated Electrograms in Brugada Syndrome Patients Arise From the Same Structurally Abnormal Subepicardial RVOT Area but Have a Different Mechanism.
Brugada syndrome (BrS) is characterized by a typical ECG pattern. We aimed to determine the pathophysiologic basis of the ST-segment in the BrS-ECG with data from various epicardial and endocardial right ventricular activation mapping procedures in 6 BrS patients and in 5 non-BrS controls. In 7 patients (2 BrS and 5 controls) with atrial fibrillation, an epicardial 8×6 electrode grid (interelectrode distance 1 mm) was placed epicardially on the right ventricular outflow tract (RVOT) before video-assisted thoracoscopic surgical pulmonary vein isolation. In 2 other BrS patients, endocardial, epicardial RV (CARTO), and body surface mapping was performed. In 2 additional BrS patients, we performed decremental preexcitation of the RVOT before endocardial RV mapping. During video-assisted thoracoscopic surgical pulmonary vein isolation and CARTO mapping, BrS patients (n=4) showed greater activation delay and more fractionated electrograms in the RVOT region than controls. Ajmaline administration increased the region with fractionated electrograms, as well as ST-segment elevation. Preexcitation of the RVOT (n=2) resulted in ECGs that supported the current-to-load mismatch hypothesis for ST-segment elevation. Body surface mapping showed that the area with ST-segment elevation anatomically correlated with the area of fractionated electrograms and activation delay at the RVOT epicardium. ST-segment elevation and epicardial fractionation/conduction delay in BrS patients are most likely related to the same structural subepicardial abnormalities, but the mechanism is different. ST-segment elevation may be caused by current-to-load mismatch, whereas fractionated electrograms and conduction delay are expected to be caused by discontinuous conduction in the same area with abnormal myocardium.


High throughput automated detection of axial malformations in Medaka embryo.
Fish embryo models are widely used as screening tools to assess the efficacy and/or toxicity of chemicals. This assessment involves the analysis of embryo morphological abnormalities. In this article, we propose a multi-scale pipeline to allow automated classification of fish embryos (Medaka: Oryzias latipes) based on the presence or absence of spine malformations. The proposed pipeline relies on the acquisition of fish embryo 2D images, on feature extraction based on mathematical morphology operators and on machine learning classification. After image acquisition, segmentation tools are used to detect the embryo before analysing several morphological features. An approach based on machine learning is then applied to these features to automatically classify embryos according to the presence of axial malformations. We built and validated our learning model on 1459 images with a 10-fold cross-validation by comparison with the gold standard of 3D observations performed under a microscope by a trained operator. Our pipeline results in correct classification in 85% of the cases included in the database. This percentage is similar to the percentage of success of a trained human operator working on 2D images. The key benefit of our approach is the low computational cost of our image analysis pipeline, which guarantees optimal throughput analysis.


New observations on the malaria parasites of rodents of the Central African Republic - Plasmodium vinckei petteri subsp. nov. and Plasmodium chabaudi Landau, 1965.
The morphology and enzyme forms of malaria parasites isolated from 50 wild caught specimens of Thamnomys rutilans from the Central African Republic have been studied and three distinct species of Plasmodium identified. One species has been confirmed as Plasmodium yoelii yoelii. Morphological features of both the remaining species correspond to those given by Landau (1965) in her original description of Plasmodium chabaudi. For one of these species the name P. chabaudi has been retained; the other species, which closely resembles subspecies of Plasmodium vinckei from other regions of Africa, has been designated Plasmodium vinckei petteri subsp. nov. P. chabaudi and P.v. petteri are distinguished from each other both in their morphology in the blood and sporogonic stages, and in their enzyme forms.


Severe herpetic keratitis. II. The costs associated with penetrating keratoplasty.
We report a study on 100 patients with severe herpetic keratitis. Overall, one in three of the study group required a penetrating keratoplasty (PK). These patients required a mean of 18 days as an inpatient and 15 outpatient visits in the year the PK was performed; these figures fell to 1 inpatient day and 8 outpatient visits in the second year after surgery. The financial cost of such therapy is discussed.


Phytochemical constituents from Salsola tetrandra.
The new norisoprenoid 3beta-hydroxy-5alpha,6alpha-epoxy-beta-ionone-2alpha-O-beta-d-glucopyranoside (1) and the long-chain hydroxy fatty acids 9,12,13-trihydroxyoctadeca-10(E),15(Z)-dienoic acid (2) and 9,12,13-trihydroxyoctadeca-10(E)-dienoic acid (3) were isolated from Salsola tetrandra aerial parts, together with 3,4,5-trimethoxyphenyl-beta-d-glucopyranoside (4), 9-hydroxylinaloyl glucoside (5), taxiphyllin (6), trans-N-feruloyltyramine (7), and S-(-)-trans-N-feruloyloctopamine (8). Their structures were elucidated by extensive spectroscopic analysis and chemical methods. Compounds 6 and 8 displayed mild antibacterial activity against Staphylococcus aureus, whereas compound 6 showed the highest activity in the Artemia salina bioassay.


Cucurbituril-based supramolecular engineered nanostructured materials.
Cucurbituril (CB) is a unique macrocycle with a rigid symmetrical structure, which is composed of two identical hydrophilic portals decorated with partially negatively charged carbonyl groups and a hydrophobic cavity. A number of different nanostructured materials, including nanoparticles, nanocomposites, vesicles and rods, have been prepared by taking advantage of the varying cavity size of the CB homologues, their ability to accommodate more than one guest in their cavities, their rigid symmetrical structures, as well as the water solubility of CB7. These nanostructures could find a wide range of potential applications in the areas of self-healing materials, nanomedicine, plasmonics, and nanocatalysis. Here, we review the recent progresses in the synthesis, properties and application of CB-based supramolecular engineered nanostructures, which are either constructed through CB-assisted self-assembly or from post-functionalized-CB homologues.


Population genetics of Amblyomma americanum (Acari: Ixodidae) collected from Arkansas.
Lone star ticks, Amblyomma americanum L. (Acari: Ixodidae),infest multiple hosts such as birds, and mammals of various sizes (rodents to white-tailed deer) and can harbor human pathogens such as Borrelia lonestari and Ehrlichiosis chaffeensis. The population structure of 251 A. americanum ticks, collected from canines and two white-tailed deer in six Arkansas ecoregions, was examined using DNA sequences of a 247-bp region of the mitochondrial DNA ribosomal RNA 16S gene. Of the 247 nucleotide characters, 26 were variable. Thirty-three haplotypes were identified of which 25 haplotypes occurred once (10%). The most common haplotype was Aa25, occurring in 60% of the samples and found in all six ecoregions. The excess of low frequency haplotypes combined with the overall negative Tajima's D and Fu and Li statistics suggests population expansion. Phylogenetic relationships of the 33 A. americanum haplotypes were constructed with other Amblyomma species and identified A. americanum as a monophyletic species with two groups. The patterns of high nucleotide and haplotype diversity found in this study suggests that the A. americanum population is expanding perhaps due to its ability to survive in a variety of habitats and feed on multiple hosts. Given the gene flow in Arkansas, the spread of acaricide resistance and pathogens may be rapid.


Bilateral anterior interosseous nerve syndromes associated with cytomegalovirus infection.
The occurrence of bilateral brachial mononeuropathies presenting as anterior interosseous nerve syndromes in association with cytomegalovirus mononucleosis in an otherwise healthy adult is reported, a relationship not previously described.


Circular RNA sequencing reveals the molecular mechanism of the effects of acupuncture and moxibustion on endometrial receptivity in patients undergoing infertility treatment.
The present study aimed to determine the profile of differentially expressed circular RNAs (circRNAs) in infertile patients treated with acupuncture and moxibustion and verify the role of acupuncture and moxibustion in altering endometrial receptivity (ER). High‑throughput RNA sequencing and bioinformatics analysis of samples from six pairs of patients treated with or without acupuncture and moxibustion were conducted. The reliability of high‑throughput RNA sequencing was validated using reverse transcription‑quantitative PCR. The most significant circRNA functions and pathways were selected by gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. A circRNA‑miR‑mRNA interaction network was constructed to determine the connection between circRNAs, microRNAs (miRs), and mRNAs. High‑throughput RNA sequencing identified 2,653 circRNAs. A total of 86 circRNAs was differentially expressed, of which 57 were upregulated and 29 were downregulated, between the acupuncture and moxibustion group and the control group. In the GO analysis, the identified BP terms were chromatin modification, positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response, oxidative DNA demethylation, regulation of transcription from RNA polymerase II promoter in response to hypoxia, and regulation of smooth muscle cell differentiation. The identified CC terms were nucleoplasm, nucleolus, nucleus, histone acetyltransferase complex, and annulate lamellae. The identified MF terms were methylcytosine dioxygenase activity, chromatin binding, zinc ion binding, histone binding, and protein binding. In the KEGG pathway analysis, the identified pathways were protein processing in endoplasmic reticulum, degradation of aromatic compounds, shigellosis, mTOR signaling pathway, bacterial invasion of epithelial cells, and prostate cancer. Circ‑SFMBT2, circ‑BACH1, and circ‑LPAR1 were significantly upregulated (P<0.05) and associated with numerous miRs and mRNAs. Acupuncture and moxibustion could impact ER by regulating the expression of circRNAs.


Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes.
Outcomes of 159 young patients with inherited metabolic disorders (IMDs) undergoing transplantation with partially HLA-mismatched unrelated donor umbilical cord blood were studied to investigate the impact of graft and patient characteristics on engraftment, overall survival (OS), and graft-versus-host disease (GVHD). Patients received myeloablative chemotherapy (busulfan, cyclophosphamide, ATG) and cyclosporine-based GVHD prophylaxis. Infused cell doses were high (7.57 x 10(7)/kg) because of the patients' young age (median, 1.5 years) and small size (median, 12 kg). Median follow-up was 4.2 years (range, 1-11 years). The cumulative incidences of neutrophil and platelet engraftment were 87.1% (95% confidence interval [CI], 81.8%-92.4%) and 71.0% (95% CI, 63.7%-78.3%). A total of 97% achieved high (> 90%) donor chimerism. Serum enzyme normalized in 97% of patients with diseases for which testings exist. Grade III/IV acute GVHD occurred in 10.3% (95% CI, 5.4%-15.2%) of patients. Extensive chronic GVHD occurred in 10.8% (95% CI, 5.7%-15.9%) of patients by 1 year. OS at 1 and 5 years was 71.8% (95% CI, 64.7%-78.9%) and 58.2% (95% CI, 49.7%-66.6%) in all patients and 84.5% (95% CI, 77.0%-92.0%) and 75.7% (95% CI, 66.1%-85.3%) in patients with high (80-100) performance score. In multivariate analysis, favorable factors for OS were high pretransplantation performance status, matched donor/recipient ethnicity, and higher infused colony forming units.


Challenges in the diagnosis and management of immune-mediated necrotising myopathy (IMNM) in a patient on long-term statins.
Immune-mediated necrotising myopathy (IMNM) is a severe and poorly understood complication of statin use. Prompt management with immunosuppressive treatment is often needed to control the condition, which differs from the management of the more commonly recognised statin-induced myopathy. We present a case report and brief review of the literature regarding the pathogenesis, diagnosis, and management of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) positive IMNM (HMGCR IMNM). There are no randomised clinical trials, but several smaller studies and cases suggest a triple therapy of corticosteroids, IVIG, and a corticosteroid-sparing immunosuppressant appears efficacious in patients with IMNM and proximal weakness. The mechanism of statin-induced IMNM is uncertain, and this is further complicated by the reports of HMGCR IMNM in statin-naïve patients, including children. We present a case of biopsy-confirmed HMGCR IMNM in a woman taking daily statins for treatment of hypercholesterolaemia for 4 years. She presented with symptoms consistent with a urinary tract infection (UTI), including muscle weakness. She was treated as an isolated case of UTI. One month later, she presented again with worsening weakness in her shoulders and hips. Creatine kinase was elevated, and MRI showed increased signal with STIR sequences in both thighs. Anti-HMGCR was positive and leg biopsy-confirmed necrotising changes. Stopping her statin prescription and a short course of prednisolone did not improve her muscle weakness. Adding methotrexate resulted in eventual resolution of her symptoms. IMNM should be considered as a differential in any patient taking statins presenting with muscle weakness, and this case suggests that immunosuppressant therapy in addition to cessation of statins is effective at treating IMNM. Clinical trials are needed to further investigate the efficacy of different combinations of immunosuppressants.


Two tyrosine residues, Tyr-108 and Tyr-503, are responsible for the deprotonation of phenolic substrates in vanillyl-alcohol oxidase.
A number of oxidoreductases from the VAO/para-cresol methylhydroxylase flavoprotein family catalyze the oxidation of para-substituted phenols. One of the best-studied is vanillyl-alcohol oxidase (VAO) from the fungus Penicillium simplicissimum For oxidation of phenols by VAO to occur, they must first be bound in the active site of the enzyme in their phenolate anion form. The crystal structure of VAO reveals that two tyrosine residues, Tyr-108 and Tyr-503, are positioned to facilitate this deprotonation. To investigate their role in catalysis, we created three VAO variants, Y108F, Y503F, and Y108F/Y503F, and studied their biochemical properties. Steady-state kinetics indicated that the presence of at least one of the tyrosine residues is essential for efficient catalysis by VAO. Stopped-flow kinetics revealed that the reduction of VAO by chavicol or vanillyl alcohol occurs at two different rates: kobs1, which corresponds to its reaction with the deprotonated form of the substrate, and kobs2, which corresponds to its reaction with the protonated form of the substrate. In Y108F, Y503F, and Y108F/Y503F, the relative contribution of kobs2 to the reduction is larger than in wild-type VAO, suggesting deprotonation is impaired in these variants. Binding studies disclosed that the competitive inhibitor isoeugenol is predominantly in its deprotonated form when bound to wild-type VAO, but predominantly in its protonated form when bound to the variants. These results indicate that Tyr-108 and Tyr-503 are responsible for the activation of substrates in VAO, providing new insights into the catalytic mechanism of VAO and related enzymes that oxidize para-substituted phenols.


Perspectives on acute coronary syndromes.
The occurrence of an acute coronary syndrome (ACS) represents a dramatic stage in the otherwise relatively slow and progressive course of coronary artery disease, bringing into perspective its life-threatening implications. The modern era of aggressive management of these syndromes was first introduced by the establishment of the coronary care unit, and later by the development of reperfusion therapies, which led, within two decades, to a reduction in death rates of ST segment elevation myocardial infarction from 30% or more to less than 10%. The insights gained into the pathophysiology of ACSs, combined with increasingly efficient risk stratification schemes in screening patients with non-ST segment ACS, have given a boost to the development of antithrombotic therapies. Acetylsalicylic acid, as well as the combination of acetylsalicylic acid and heparin with the addition of an intravenous glycoprotein IIb/IIIa antagonist and/or the addition of an ADP P2Y12 receptor blocker, when combined with an invasive strategy targeting revascularization of the culprit coronary lesion (when appropriate), have successfully reduced the rates of adverse clinical outcomes in non-ST segment elevation ACS from 25% to 10%. These rates, however, did not improve further during the past few years, while the number of such patients is increasing to now account for the majority of admissions to coronary care units. A new research focus in cardiology is emerging, following the discovery that culprit lesions may be multiple and multifocal in association with a more diffuse inflammatory state. New therapeutic frontiers are thus being suggested to control the most fundamental mechanisms involved in ACSs and related to inflammation and autoimmunity.


[Antibody response in mice, rabbits and pigs in response to vaccination with an inactivated oil vaccine containing rotavirus and Escherichia coli strains with K88, K99 and 987P fimbrial antigens].
In trials with mice, rabbits and weanling piglets, four experimental charges of a combined inactivated oil vaccine against diarrhoeas in mammals were tested: the vaccine was to be implanted to sows and it contained porcine rotavirus (PRV); two charges also contained bovine rotavirus and bacterins of enterotoxicogenic strains of E. coli with protective antigens K88, K99 and 987P. At low starting antibody titres the twofold i.m. implantation of 0.2 ml vaccine stimulated in mice the production of antibodies to reach the average titre value of 1:128 against PRV and of 1:256 against BRV; in rabbits the twofold i.m. implantation of 2 ml vaccine stimulated the antibody development to reach the average titres of 1:508 or 1:500, and in weanlings after the twofold i. m. implantation of the vaccine the titres were 1:1028 or 1:469; in mice agglutination antibodies to antigen K88 had the average value of 1:68, to antigen K99 the value of 1:44 and to antigen 987P the value of 1:8192; in rabbits the respective titres were 1:285, 1:136 and 1:6006 and in pigs 1:570, 1:631 and 1:8192. The antibodies to antigen 987P persisted at the same level in pigs for six months. Even though there was a gradual decrease in the antibodies to antigens K88 and K99, at that time the values were 9.8 times, or 15.2 times higher than the starting values, and only the antibodies to PRV dropped to the pre-vaccination level. Repeated administration of vaccine to pigs after six months from revaccination induced, with the exception of antigen 987P, an increase in antibodies in a fortnight to reach such titres that were recorded after revaccination.


[Hypertension and intermittent convulsions for one month in a school-age child].
Childhood polyarteritis nodosa (PAN) is a rare systemic vasculitis and the delayed diagnosis and treatment will cause high incidence of sequelae and high mortality. This article reports a girl with childhood PAN due to posterior reversible encephalopathy syndrome (PRES). The girl aged ten years was admitted to the hospital due to hypertension and convulsions for one month. She had complaints of headache, vomiting, and blurred vision before convulsions. At six months before admission, a mass was observed in the neck. The physical examination showed that she had hypertension and no abnormal findings in the central nervous system. The brain magnetic resonance imaging manifested long T1 and T2 signals, high signal intensities on fluid-attenuated inversion recovery (FLAIR) images, and iso-signal intensity on diffusion-weighted imaging in the white matter of the left occipital lobe. Therefore, the cause of convulsions was considered as PRES. Mass biopsy suggested PAN and no findings supported tuberculosis. The right kidney atrophy was observed by ultrasound examination. Emission computed tomography of the kidney showed multiple vascular stenosis and no blood perfusion in the right kidney, so PAN was confirmed. These findings suggest that PAN should be considered in patients with vasculitis who had involvements of multiple systems after excluding common vasculitis, such as Kawasaki disease and Henoch-Schönlein purpura. Biopsy and angiography should be performed as early as possible for timely diagnosis and treatment.


Papillary cystadenocarcinoma of the lacrimal gland.
A 35-year-old man complained of progressive exophthalmos on the left eye for six months. MRI revealed approximately 18 mm x 17 mm cyst neoplasm across the inner and outer muscle cone in the left orbital cavity. Extraction was performed. The cyst wall of the tumor had the infiltration of the cancer cells and contained the residual lacrimal gland tissue. The patient refused further cranio-orbital resection or preoperative/postoperative radiotherapy or chemotherapy. Following for nine years found no local recurrence or systemic metastasis.


Association between radiation dose and pathological complete response after preoperative radiochemotherapy in esophageal squamous cell cancer.
This study was undertaken to examine the impact of radiation dose on pathological complete response (pCR) rates following neoadjuvant radiochemotherapy (N-RCT) for squamous cell esophageal cancer (ESCC). From 1988 to 2011, 218 patients were treated with 30-30.6 Gy (1.8-2 Gy per fraction), 39.6-40 Gy (1.8-2 Gy per fraction) or 44-45 Gy (1.8-2 Gy per fraction) and concomitant cisplatin ± 5-fluorouracil (5-FU), oxaliplatin + 5-FU or 5-FU alone. The most commonly used concomitant chemotherapy was continuous infusion of 5-FU-alone with a dose of 300 mg/m(2)/day during the whole course of treatment (n=111). To eliminate the dispersing effect of potentially different efficacy levels of these drug regimens on pCR, we excluded patients with regimens other than 5-FU-alone. Histomorphological regression grade 1a (0% residual tumor), 1b (<10% residual tumor), 2 (10-50% residual tumor) and 3 (>50% residual tumor) was observed in 26 (23%), 24 (22%), 36 (32%) and 25 (23%) patients, respectively. pCR was observed in 9 out of 71 (13%) patients treated with 30 Gy-30.6 Gy, 13 of 34 (38%) patients treated with 39.6-40 Gy and 4 of 6 (67%) patients treated with 44-45 Gy (p=0.001). Median follow-up time from the start of N-RCT was 191 months (range=2-262 months). The estimated 5-year overall survival (OS) was 33% for the whole cohort. OS at 5 years was 58% for patients with pCR compared to 25% for patients with less favorable response to N-RCT (p=0.009), respectively. The dose of radiation correlates significantly with the likelihood of achieving a pCR in stage II/III squamous cell esophageal cancer patients. Prospective randomized trials are required to definitively evaluate the impact of application of higher radiation doses on efficacy and safety/tolerability in the context of N-RCT on the clinical outcomes.


PHENOTYPIC PLASTICITY IN POLYGONUM PERSICARIA. I. DIVERSITY AND UNIFORMITY IN GENOTYPIC NORMS OF REACTION TO LIGHT.
Several aspects of genotype-environment interaction may act to modulate natural selection in populations that encounter variable environments. In this study the norms of reaction (phenotypic responses) of 20 cloned genotypes from two natural populations of the annual plant Polygonum persicaria were determined over a broad range of controlled light environments (8%-100% full sun). These data reveal both the extent of functionally adaptive phenotypic plasticity expressed by individual genotypes, and the patterns of diversity among genotypes for characters relevant to fitness, in response to an environmental factor that is both highly variable within populations and critical to growth and reproduction.


Diversity of Cell Wall Related Proteins in Human Pathogenic Fungi.
The cell wall is one of the major keys to fungal identity. Fungi use their cell wall to sense the environment, and localize nutrients and competing microorganism. Pathogenic species additionally modify their cell walls to hide from a host's immune system. With the growing number of fungal infections and alarming shortage of available drugs, we are in need of new approaches to fight pathogens. The cell wall seems to be a natural target, since animal host cells are devoid of it. The current knowledge about fungal cell wall components is often limited, and there is huge diversity both in structure and composition between species. In order to compare the distribution of diverse proteins involved in cell wall biosynthesis and maintenance, we performed sequence homology searches against 24 fungal proteomes from distinct taxonomic groups, all reported as human pathogens. This approach led to identification of 4014 cell wall proteins (CWPs), and enabled us to speculate about cell wall composition in recently sequenced pathogenic fungi with limited experimental information. We found large expansions of several CWP families, in particular taxa, and a number of new CWPs possibly involved in evading host immune recognition. Here, we present a comprehensive evolutionary history of fungal CWP families in the context of the fungal tree of life.


A Case of Odontogenic Infection by Streptococcus constellatus Leading to Systemic Infection in a Cogan's Syndrome Patient.
Odontogenic infection in immunocompromised patients tends to extend systemically beyond the oral cavity. Our case report presents a patient with sepsis due to a Streptococcus constellatus (S. constellatus) odontogenic infection in a 64-year-old-immunocompromised woman with Cogan's syndrome. She had been suffering from chronic mandibular osteomyelitis which was thought to have been caused by dental caries and/or chronic periodontitis with furcation involvement of the left mandibular first molar. We suspect that the acute symptoms of the chronic osteomyelitis due to S. constellatus led to the systemic infection. This infection could be accelerated by the use of a corticosteroid and an alendronate. This is the first report which represents the potential association between odontogenic infection and Cogan's syndrome.


Generating energetic electrons through staged acceleration in the two-plasmon-decay instability in inertial confinement fusion.
A new hot-electron generation mechanism in two-plasmon-decay instabilities is described based on a series of 2D, long-term (~10 ps) particle-in-cell and fluid simulations under parameters relevant to inertial confinement fusion. The simulations show that significant laser absorption and hot-electron generation occur in the nonlinear stage. The hot electrons are stage accelerated from the low-density region to the high-density region. New modes with small phase velocities develop in the low-density region in the nonlinear stage and form the first stage for electron acceleration. Electron-ion collisions are shown to significantly reduce the efficiency of this acceleration mechanism.


Chronic block of the cervical trunk increases synaptic efficacy in the superior and stellate ganglia of the guinea-pig.
1. The effects of chronic conduction block with tetrodotoxin (TTX) of the cervical sympathetic trunk on synapses in the superior and stellate ganglia were examined in vitro with intracellular recording techniques. 2. The mean maximum amplitude of excitatory post-synaptic potentials (e.p.s.p.s) evoked in superior cervical ganglion neurones by stimulation of the cervical sympathetic trunk was increased significantly after 2 or 4 days of block. The electrical properties of the ganglion cells were not appreciably changed by the period of inactivity. 3. Chronic conduction block for 4 days also resulted in a significant increase in the amplitude of the e.p.s.p.s. evoked in stellate ganglion cells by active collaterals of the blocked fibres. 4. The number of steps in the synaptic response elicited in individual stellate ganglion neurones by graded stimulation of the ansa subclavia and the subclavian trunk (which join to form the cervical sympathetic trunk) was increased after 4 days of conduction block. 5. These results show that elimination of impulse activity in the cervical sympathetic trunk increased synaptic efficacy at the disused synapses in the superior cervical ganglion and at the active synapses in the stellate ganglion. In the latter case, collaterals of the blocked fibres apparently formed new synaptic connexions on stellate ganglion cells.


Defect-Laden MoSe2 Quantum Dots Made by Turbulent Shear Mixing as Enhanced Electrocatalysts.
A high density of edge sites and other defects can significantly improve the catalytic activity of layered 2D materials. Herein, this study demonstrates a novel top-down strategy to maximize catalytic edge sites of MoSe2 by breaking up bulk MoSe2 into quantum dots (QDs) via "turbulent shear mixing" (TSM). The ultrasmall size of the MoSe2 QDs provides a high fraction of atoms in reactive edge sites, thus significantly improving the catalytic activities. The violent TSM further introduces abundant defects as additional active sites for electrocatalytic reactions. These edge-proliferated and defect-laden MoSe2 QDs are found to be efficient electrocatalysts for the hydrogen evolution reaction, and useful as counter electrodes in dye-sensitized solar cells. The work provides a new paradigm for creating edge-proliferated and defect-rich QDs from bulk layered materials.


[Comparison of objective assessment using the sweep pattern visual evoked response acuity (SPVERA) and illiterate E visual acuity].
To compare the vision objectively assessed by SPVERA with the illiterate E Acuity in normal subjects. The effect of artificially induced image defocusing on visual acuities (Vas) measured by SPVEP and illiterate E chart measurement was studied in 14 normal subjects. SPVEP was recorded using vertical gratings of 8 different spatial frequencies ranging from 0.235 9 to 30.203 2 c/deg. The responses were averaged and displayed through the discrete Fourier transform on the monitor display. SPVERA was determined by extrapolating the PVER amplitude -spatial frequency function to baseline. SPVERA was compared with illiterate E visual acuity measured under the same conditions of optical defocus. With moderate defocusing (<+1.0 diopter (D),VA > 0.42), the SPVERA were equal to or poorer than the illiterate E visual acuity. With more defocus (> +2.0 diopter (D), VA < 0.3),the SPVERA became better than the illiterate E chart Visual Acuity. The correlation between the two acuities was r2 = 0.919. SPVERA and the illiterate E visual acuity correlated to a certain degree. We conclude that the SPVERA is effective in estimating vision objectively.


Kidney function, proteinuria and breast arterial calcification in women without clinical cardiovascular disease: The MINERVA study.
Breast arterial calcification (BAC) may be a predictor of cardiovascular events and is highly prevalent in persons with end-stage kidney disease. However, few studies to date have examined the association between mild-to-moderate kidney function and proteinuria with BAC. We prospectively enrolled women with no prior cardiovascular disease aged 60 to 79 years undergoing mammography screening at Kaiser Permanente Northern California between 10/24/2012 and 2/13/2015. Urine albumin-to-creatinine ratio (uACR), along with specific laboratory, demographic, and medical data, were measured at the baseline visit. Baseline estimated glomerular filtration rate (eGFR), medication history, and other comorbidities were identified from self-report and/or electronic medical records. BAC presence and gradation (mass) was measured by digital quantification of full-field mammograms. Among 3,507 participants, 24.5% were aged ≥70 years, 63.5% were white, 7.5% had eGFR <60 ml/min/1.73m2, with 85.7% having uACR ≥30 mg/g and 3.3% having uACR ≥300 mg/g. The prevalence of any measured BAC (>0 mg) was 27.9%. Neither uACR ≥30 mg/g nor uACR ≥300 were significantly associated with BAC in crude or multivariable analyses. Reduced eGFR was associated with BAC in univariate analyses (odds ratio 1.53, 95% CI: 1.18-2.00), but the association was no longer significant after adjustment for potential confounders. Results were similar in various sensitivity analyses that used different BAC thresholds or analytic approaches. Among women without cardiovascular disease undergoing mammography screening, reduced eGFR and albuminuria were not significantly associated with BAC.


Validation of temporal gait metrics from three IMU locations to the gold standard force plate.
The purpose of this work is to compare temporal gait parameters from three different IMU locations to the gold standard force platform. 33 subjects (12 F, 21 M) performed twenty gait trials each while wearing inertial measurement units (IMUs) on the trunk, both shanks and both feet. Data was simultaneously collected from a laboratory embedded force plate. Step times were derived from the raw IMU data at the three IMU locations using methods that have been shown to be accurate. Step times from all locations were valid compared to the force plate. Foot IMU step time was the most accurate (Pearson = .991, CI width = 3.00e2), the trunk IMU was the next most accurate (Pearson = .974, CI width = 4.85e2) and shank step time was the least accurate (Pearson = .958, CI width = 6.80e2). All three sensing locations result in valid estimations of step time compared to the gold standard force plate. These results suggest that the foot location would be most appropriate for clinical applications where very precise temporal parameter detection is required.


Transport and retention mechanisms govern lipid droplet inheritance in Saccharomyces cerevisiae.
Lipid droplets are ubiquitous cellular structures involved in energy homeostasis and metabolism that have long been considered as simple inert deposits of lipid. Here, we show that lipid droplets are bona fide organelles that are actively partitioned between mother cell and daughter cell in Saccharomyces cerevisiae. Video microscopy revealed that a subset of lipid droplets moves from mother cell to bud in an ordered, vectorial process, while the remaining lipid droplets are retained by the mother cell. Bud-directed movement of lipid droplets is mediated by the molecular motor Myo2p, while retention of lipid droplets occurs at the perinuclear endoplasmic reticulum. Lipid droplets are thus apportioned between mother cell and daughter cell at cell division rather than being made anew.


A Pragmatic Approach Identifies a High Rate of Nonalcoholic Fatty Liver Disease With Advanced Fibrosis in Diabetes Clinics and At-Risk Populations in Primary Care.
Noninvasive serum biomarkers (nonalcoholic fatty liver disease fibrosis score [NFS], fibrosis 4 score [FIB-4], or enhanced liver fibrosis [ELF] test) are recommended as first-line tools to determine the risk of advanced fibrosis in nonalcoholic fatty liver disease. We aimed to assess the utility of a pragmatic approach to screening for clinically significant fibrosis in primary care and diabetes clinics. We recruited 252 patients from an endocrine clinic or primary care facility. Anthropometric measurements, ELF test, ultrasound, and liver stiffness measurements (LSMs) were performed. Clinically significant fibrosis was defined as LSM ≥8.2 kPa or ELF ≥9.8. A subgroup of patients underwent liver biopsy (n = 48) or had imaging diagnostic of cirrhosis (n = 14). Patients were 57.3 ± 12.3 years old with a high prevalence of metabolic syndrome (84.5%), type 2 diabetes (82.5%), and body mass index (BMI) ≥40 kg/m2 (21.8%). LSM met quality criteria in 230 (91.3%) patients. NFS and FIB-4 combined had a high negative predictive value (90.0%) for excluding LSM ≥8.2 kPa. However, 84.1% of patients had indeterminate or high NFS or FIB-4 scores requiring further assessment. LSM ≥8.2 kPa and ELF ≥9.8 were present in 31.3% and 28.6% of patients, respectively. Following adjustment for age, BMI, sex, and presence of advanced fibrosis, older age was independently associated with ELF ≥9.8 (adjusted odds ratio, 1.14; 95% confidence interval, 1.06-1.24), whereas increasing BMI was independently associated with LSM ≥8.2 kPa (adjusted odds ratio, 1.15; 95% confidence interval, 1.01-1.30). Concordant LSM <8.2 kPa and ELF <9.8 and concordant LSM ≥8.2 kPa and ELF ≥9.8 had a high negative predictive value (91.7%) and positive predictive value (95.8%) for excluding and identifying clinically significant fibrosis, respectively. Conclusion: Simple scoring tools alone lack accuracy. LSM accuracy is influenced by severe obesity, whereas age impacts the ELF test. Further studies are required to confirm whether combining LSM and ELF may enhance accuracy and confidence in identifying clinically significant fibrosis. (Hepatology Communications 2018; 00:000-000).


Enzyme-based multiplexer and demultiplexer.
A digital 2-to-1 multiplexer and a 1-to-2 demultiplexer were mimicked by biocatalytic reactions involving concerted operation of several enzymes. Using glucose oxidase (GOx) and laccase (Lac) as the data input signals and variable pH as the addressing signal, ferrocyanide oxidation in the output channel was selectively activated by one from two inputs, thus mimicking the multiplexer operation. A demultiplexer based on the enzyme system composed of GOx, glucose dehydrogenase (GDH) and horseradish peroxidase (HRP) allowed selective activation of different output channels (oxidation of ferrocyanide or reduction of NAD(+)) by the glucose input. The selection of the output channel was controlled by the addressing input of NAD(+). The designed systems represent important novel components of future branched enzyme networks processing biochemical signals for biosensing and bioactuating.


Cavitands as Chaperones for Monofunctional and Ring-Forming Reactions in Water.
Cyclic processes involving medium-sized rings show low rates because internal strains-torsions and transannular interactions-are created during the reactions. High dilution is often used to slow the competing bi- and higher-molecular processes but cannot accelerate the desired cyclization reaction. Here we apply cavitands to the formation of medium- to large-sized rings through conversion of long-chain diisocyanates to cyclic ureas. The reactions take place in aqueous (D2O) solution, where hydrophobic forces drive the starting materials into the cavitands in folded conformations. The guest assumes the shape to fill the space properly, which brings the reacting ends closer together than they are in bulk solvent. Complexation overcomes some of the internal strains involved in precyclization shapes of the guest molecules and accelerates the cyclization. The results augur well for applications of water-soluble cavitands to related processes such as remote functionalization reactions.


Expression of EGF, TGF-alpha, EGFR and c-erbB2 genes and their gene products in human pancreatic carcinoma cell lines.
The expression of mRNA for epidermal growth factor (EGF), transforming growth factor-alpha (TGF-alpha), EGF receptor (EGFR) and c-erbB-2 genes and the immunoreactivity to these gene products were examined in 3 newly established human pancreatic carcinoma cell lines and their corresponding in vivo tumor lines using the Northern blot technique and the immunohistochemical method. All 3 cell lines expressed TGF-alpha, EGFR and 2 of the 3 lines expressed EGF and c-erbB-2 mRNAs. The immunohistochemical study showed immunoreactivity to EGF, TGF-alpha and EGFR in all these 3 cell lines and their corresponding in vivo tumor lines. These results indicate that the autocrine loop of EGF and/or TGF-alpha/EGFR in pancreatic carcinoma cells may be one of the important reasons for the uncontrolled growth of the pancreatic carcinoma. The c-erbB-2 overexpression in some of the cell lines may also contribute to the carcinogenesis or progression of this cancer.


Atrial tachycardias arising from ablation of atrial fibrillation: a proarrhythmic bump or an antiarrhythmic turn?
The occurrence of atrial tachycardias (AT) is a direct function of the volume of atrial tissue ablated in the patients with atrial fibrillation (AF). Thus, the incidence of AT is highest in persistent AF patients undergoing stepwise ablation using the strategic combination of pulmonary vein isolation, electrogram based ablation and left atrial linear ablation. Using deductive mapping strategy, AT can be divided into three clinical categories viz. the macroreentry, the focal and the newly described localized reentry all of which are amenable to catheter ablation with success rate of 95%. Perimitral, roof dependent and cavotricuspid isthmus dependent AT involve large reentrant circuits which can be successfully ablated at the left mitral isthmus, left atrial roof and tricuspid isthmus respectively. Complete bidirectional block across the sites of linear ablation is a necessary endpoint. Focal and localized reentrant AT commonly originate from but are not limited to the septum, posteroinferior left atrium, venous ostia, base of the left atrial appendage and left mitral isthmus and they respond quickly to focal ablation. AT not only represents ablation-induced proarrhythmia but also forms a bridge between AF and sinus rhythm in longstanding AF patients treated successfully with catheter ablation.


[Practical training adopted from essential laboratory tests in laboratory medicine].
A proposal of essential laboratory tests, made by the Japan Society of Clinical Pathology in 1989, was applied to the education of medical students in Tokushima University. The effects of this proposal on lecture and practice of laboratory medicine were evaluated by obtaining information through a questionnaire from students and clinicians. Our curriculum of laboratory medicine generally received good assessment from students and my opinion and practical training on essential laboratory tests were understood by them. The mean coefficient of variation of intra-assay precision was 3.7% and mean recovery was 70.3 at the measurement for serum protein concentration, which is one of the items in the essential laboratory tests. However, the quality of this experiment was not in accordance with the scholarly attainments or the results of the state examination for physicians. The clinicians in service at the medical school have more selected items than items of essential laboratory tests both at the initial outpatient examination and at hospital admission. Therefore, essential laboratory tests in daily primary medical care may be considered from a different standpoint, when used in the education of laboratory medicine.


Birefringent Fourier transform imaging spectrometer with a rotating retroreflector.
A birefringent Fourier transform imaging spectrometer with a new lateral shearing interferometer is presented. The interferometer includes a Wollaston prism and a retroreflector. It splits an incident light beam into two shearing parallel parts to obtain interference fringe patterns of an imaging target, which is well established as an aid in reducing problems associated with optical alignment and manufacturing precision. Continuously rotating the retroreflector enables the spectrometer to acquire two-dimensional spectral images without spatial scanning. This technology, with a high work efficiency and low complexity, is inherently compact and robust. The effectiveness of the proposed method is demonstrated by the experimental results.


Induction of antigen-specific regulatory T cells in the liver-draining celiac lymph node following oral antigen administration.
Regulatory T cells are induced by oral administration of an antigen, but the physiological requirements and localization of the inductive sites are largely unknown. Using an adoptive transfer system of cells transgenic for ovalbumin T-cell receptor (OVA TCR tg), we found that antigen-specific CD4+ T cells were activated in the liver-draining celiac lymph node (CLN) shortly after ovalbumin feeding, and that a significantly higher proportion of the T cells in the CLN developed into the putative regulatory phenotype [co-expressing CD25 with the glucocortico-induced tumour necrosis factor (TNF) receptor family related gene (GITR), cytotoxic T-lymphocyte antigen (CTLA)-4 and CD103] than in Peyer's patches, the mesenteric and peripheral lymph nodes and the spleen. In addition, a particularly high level of expression of CD103 on the OVA-specific T cells in the CLN may favour homing to the epithelium of the intestine. While equally suppressive, OVA tg T cells isolated from the CLN of OVA-fed DO11.10 mice were less dependent on transforming growth factor (TGF)-beta for suppression than cells isolated from the peripheral and mesenteric lymph nodes, which indicates the involvement of an additional suppressive mechanism. The expression of FoxP3 was not up-regulated in any of the lymph node compartments studied. Our phenotypic and functional findings suggest that the induction of regulatory T cells in the CLN may be relevant in the control of the immune response to dietary antigens.


The role of hazardous drinking reductions in predicting depression and anxiety symptom improvement among psychiatry patients: A longitudinal study.
Co-occurrence of depression, anxiety, and hazardous drinking is high in clinical samples. Hazardous drinking can worsen depression and anxiety symptoms (and vice versa), yet less is known about whether reductions in hazardous drinking improve symptom outcomes. Three hundred and seven psychiatry outpatients were interviewed (baseline, 3-, 6-months) for hazardous drinking (drinking over recommended daily limits), depression (PHQ-9), and anxiety (GAD-7) as part of a hazardous drinking intervention trial. Longitudinal growth models tested associations between hazardous drinking and symptoms (and reciprocal effects between symptoms and hazardous drinking), adjusting for treatment effects. At baseline, participants had moderate anxiety (M=10.81; SD=10.82) and depressive symptoms (M=13.91; SD=5.58); 60.0% consumed alcohol at hazardous drinking levels. Over 6-months, participants' anxiety (B=-3.03, p<.001) and depressive symptoms (B=-5.39, p<.001) improved. Continued hazardous drinking led to slower anxiety (B=0.09, p=.005) and depressive symptom (B=0.10, p=.004) improvement; reductions in hazardous drinking led to faster anxiety (B=-0.09, p=.010) and depressive (B=-0.10, p=.015) symptom improvement. Neither anxiety (B=0.07, p=.066) nor depressive (B=0.05, p=.071) symptoms were associated with hazardous drinking outcomes. Participants were psychiatry outpatients, limiting generalizability. Reducing hazardous drinking can improve depression and anxiety symptoms but continued hazardous use slows recovery for psychiatry patients. Hazardous drinking-focused interventions may be helpful in promoting symptom improvement in clinical populations.


Basic and clinical aspects of the alpha1-antitrypsin.
A deficiency of the major serum alpha1-globulin, the alpha1-antitrypsin, was first described in five patients by Laurell and Eriksson in Sweden in 1963. It soon became obvious that severe alpha1-antitrypsin deficiency was familial, and highly associated with chronic lung disease, having its onset in the third or fourth decade of life. Since the early descriptions of this common deficiency state, it has become clearly associated with familial emphysema in some families, familial infantile cirrhosis in others, and occasionally with a combination of childhood lung and liver disease in siblings. For the pediatrician, severe alpha1-antitrypsin deficiency now enters into the differential diagnosis of both chronic pulmonary disease in childhood and obstructive jaundice in the newborn period; In addition, low levels of alpha1-antitrypsin in serum are characteristic of respiratory distress syndrome, and elevations of this protein may be found in a variety of clinical situations. The, alpha1-antitrypsin probably functions as a major control protein against the tissue-damaging effects of both endogenous and exogenous enzymes. This review will cover several basic and clinical features of this protein with respect to its importance in pediatrics.


The effect of human immunodeficiency virus on sperm parameters and the outcome of intrauterine insemination following sperm washing.
This is the first study to assess the outcome of sperm washing and intrauterine insemination (IUI) cycles in human immunodeficiency virus-positive (HIV(+)) men to determine any predictors of success, as well as evaluating the effect of HIV on sperm parameters. Semen characteristics were evaluated in 106 HIV(+) men and a control group of 234 HIV(-) men, and the effect of markers of HIV disease assessed. Age, stimulation regime, sperm parameters, markers of HIV disease and the use of anti-retrovirals were assessed as predictors of the outcome of sperm washing/IUI cycles in the HIV(+) men. Ejaculate volume, sperm concentration, total count, progressive motility and normal morphology were all significantly higher in the control group compared to the HIV(+) men (P<0.05). A significant positive correlation was observed between CD4 count and sperm concentration, total count, motility, progressive motility type 'a'+'b' and post-preparation concentration and a significant negative correlation with normal sperm morphology of both raw and post-preparation samples. No correlation was observed between viral load (VL), years since diagnosis, use of anti-retrovirals or duration of use and any sperm parameter. The only factors that significantly improved IUI outcome were a VL <1000 copies/ml and the use of anti-retrovirals. These data demonstrate that sperm parameters are significantly impaired by the presence of HIV infection and in particular correlate with CD4 count. Undetectable VL and the use of anti-retrovirals improve the outcome of IUI/sperm washing in HIV(+) men.


Energy and nutrient intakes of independently-living, elderly women.
A descriptive study was conducted to determine the energy and nutrient intakes of 34 independently-living, elderly women. Data were collected using the 24-hour recall method, and compared to the 1990 Canadian Recommended Nutrient Intakes (RNI) for elderly women. Mean intakes of energy, calcium, and zinc were below recommended levels for the sample as a whole. The mean intake of folate was below recommendation for women in the age group 65 to 74 years. All other dietary intakes met or exceeded recommended amounts. No statistically significant differences were observed for energy or selected nutrient intakes by age (65 to 74 years old versus 75 to 83) or living arrangement (alone versus with other). Nutrition is an important aspect of health, and more nursing interventions can help elderly women to choose diets that support optimal health. Further comprehensive nutrition studies are needed to provide the relevant knowledge base.


Identification of a novel mutation in the arginine vasopressin-neurophysin II gene in familial central diabetes insipidus.
Familial central diabetes insipidus is an inherited disease of predominant autosomal dominant trait characterized by a deficiency of arginine vasopressin. The arginine vasopressin-neurophysin II ( AVP-NPII) gene consists of three exons and is located on chromosome 20p13 encoding for the precursor protein of AVP. We investigated two Caucasian families with a typical autosomal dominant trait of familial central diabetes insipidus, defined by deficiency of arginine vasopressin. After PCR amplification of exon 1 and exon 2/3, fragments were pooled and purified. Nucleotide sequencing was performed with the Taq DyeDeoxy-terminator cycle sequencing method using nested primers. Two mutations in the coding region of NPII were identified. In family C we found a heterozygous G ==> C missense mutation (AA61) in exon 2 leading to the substitution of cystein with serine. In family D a novel heterozygous nonsense mutation in exon 3 (AA 83, GAG ==> TAG) was indentified, leading to a stop codon instead of glutamine. Both mutations were confirmed by restriction analysis and were found in all affected but not in healthy family members or control subjects. We therefore have identified a missense mutation of the AVP-NPII gene and a novel mutation predicting a truncated protein.


Diosgenin glucoside protects against myocardial injury in diabetic mice by inhibiting RIP140 signaling.
Myocardial injury is often observed during diabetes, but the nature physiological association is unclear. Here, we investigated the protective effective of diosgenin glucoside (DG), a pharmacologically active saponin extracted from Tritulus terrestris L., against myocardial injury in type 2 diabetic (db/db) mice and its molecular mechanism of action. Levels of serum and myocardial tissues, blood glucose and inflammatory cytokines, as well as cardiac function indicators, of db/db mice were measured, and DG's mechanism of action was evaluated by immunohistochemistry and Western blotting. We found that long-term DG treatment improved glucose tolerance and lipid profiles, reduced production of IL-1β, IL-6, and TNF-α, and decreased serum levels of the cardiac injury indicators creatine kinase and lactate dehydrogenase. Interestingly, DG also inhibited RIP140 signaling, which normally regulates transcription of estrogen receptor genes and influences expression of proinflammatory cytokines. Our study revealed a novel mechanism of DG's anti-inflammatory effect against myocardial injury via RIP140 signaling modulation in diabetic mice.


Opana-induced thrombotic microangiopathy masquerading as thrombotic thrombocytopenic purpura.
Opana (oxymorphone) is a powerful semi-synthetic opioid agonist used for chronic pain management that is ingested orally. However, improper injection of Opana can lead to a rare and fatal blood disorder known as thrombotic microangiopathy. Opana-induced thrombotic microangiopathy can be easily mistaken for thrombotic thrombocytopenic purpura (TTP), leading to the initiation of therapeutic plasma exchange. Current literature has conflicting views on the necessity of therapeutic plasma exchange for the treatment of Opana-induced thrombotic microangiopathy. In our case report, a 47-year-old Caucasian male was admitted with a presentation suspicious for TTP then underwent therapeutic plasma exchange without clinical improvement. With supportive treatment only, the patient eventually improved and later admitted to intravenously abusing oral Opana 1-2 days prior to becoming ill.


Optimal timing and frequency of bone marrow soup therapy for functional restoration of salivary glands injured by single-dose or fractionated irradiation.
Injections of bone marrow (BM) cell extract, known as 'BM soup', were previously reported to mitigate ionizing radiation (IR) injury to salivary glands (SGs). However, the optimal starting time and frequency to maintain BM soup therapeutic efficacy remains unknown. This study tested the optimal starting time and frequency of BM soup injections in mice radiated with either a single dose or a fractionated dose. First, BM soup treatment was started at 1, 3 or 7 weeks post-IR; positive (non-IR) and negative (IR) control mice received injections of saline (vehicle control). Second, BM soup-treated mice received injections at different frequencies (1, 2, 3 and 5 weekly injections). Third, a 'fractionated-dose radiation' model to injure mouse SGs was developed (5 Gy × 5 days) and compared with the single high dose radiation model. All mice (n = 65) were followed for 16 weeks post-IR. The results showed that starting injections of BM soup between 1 and 3 weeks mitigated the effect of IR-induced injury to SGs and improved the restoration of salivary function. Although the therapeutic effect of BM soup lessens after 8 weeks, it can be sustained by increasing the frequency of weekly injections. Moreover, both single-dose and fractionated-dose radiation models are efficient and comparable in inducing SG injury and BM soup treatments are effective in restoring salivary function in both radiation models. In conclusion, starting injections of BM soup within 3 weeks post-radiation, with 5 weekly injections, maintains 90-100% of saliva flow in radiated mice.


Immunomodulation by biphalin, dimeric synthetic opioid peptide, and its analog.
The opioid pentapeptides called enkephalins were originally described as the endogenous ligands for the opioid receptors. Although their precise physiological significance still remains elusive, the enkephalins have been reported to exhibit analgesic, antidepressant, antianxiety and anticonvulsant activities. In addition, enkephalins have also been shown to act as immunomodulator. The first generation of dimeric peptides was derived from enkephalins. Biphalin [(Tyr-D-Ala-Gly-Phe-NH)2] is a bivalent opioid analog containing two tyrosine residues. We have evaluated the immunomodulatory properties of biphalin and its analogs in various in vitro tests. We report that biphalin and one of its analogs [Tyr-D-Ala-Gly-Phe-NH.NH-Phe(p-Cl)-H] stimulate human T cell proliferation, natural killer (NK) cell cytotoxicity in vitro and interleukin-2 (IL-2) production. Biphalin and its analog also released chemokine like factor in the culture supernatant that was responsible for increased chemotaxis of monocytes. Furthermore, these peptides inhibited tumor necrosis factor (TNF-alpha) production in lipopolysaccharide (LPS) stimulated peripheral blood mononuclear cells (PBMC) and nitric oxide (NO) production in mouse macrophage cells, RAW 264.7. Our observations suggest immunomodulatory property of biphalin and its analog.


Wound healing strategies based on nanoparticles incorporated in hydrogel wound patches.
The intricate, tightly controlled mechanism of wound healing that is a vital physiological mechanism is essential to maintaining the skin's natural barrier function. Numerous studies have focused on wound healing as it is a massive burden on the healthcare system. Wound repair is a complicated process with various cell types and microenvironment conditions. In wound healing studies, novel therapeutic approaches have been proposed to deliver an effective treatment. Nanoparticle-based materials are preferred due to their antibacterial activity, biocompatibility, and increased mechanical strength in wound healing. They can be divided into six main groups: metal NPs, ceramic NPs, polymer NPs, self-assembled NPs, composite NPs, and nanoparticle-loaded hydrogels. Each group shows several advantages and disadvantages, and which material will be used depends on the type, depth, and area of the wound. Better wound care/healing techniques are now possible, thanks to the development of wound healing strategies based on these materials, which mimic the extracellular matrix (ECM) microenvironment of the wound. Bearing this in mind, here we reviewed current studies on which NPs have been used in wound healing and how this strategy has become a key biotechnological procedure to treat skin infections and wounds.