In vitro activity of netilmicin against clinical isolates of methicillin resistant and susceptible Staphylococcus aureus.
The emergence of methicillin-resistant Staphylococcus aureus and its multidrug-resistant property has led to the search for an effective antibiotic to combat staphylococcal sepsis. At present, vancomycin remains the most effective antibiotic. This study evaluated the in vitro efficacy of netilmicin (an aminoglycoside) and compared its activity with 4 other antibiotics, viz. vancomycin, amikacin, tobramycin and ofloxacin. The minimum inhibitory concentration of the antibiotics was determined by the agar dilution method. Thirty strains each of methicillin-resistant and -susceptible S. aureus isolated from pus and blood cultures were included. The susceptibility to netilmicin was found to be 100% and was the same as that observed for vancomycin. All the methicillin-resistant S. aureus strains tested showed 100% susceptibility to netilmicin, suggesting its use in patients with such infections as an alternative to vancomycin. However, this finding needs to be verified in the clinical setting.


CAR race to cancer immunotherapy: from CAR T, CAR NK to CAR macrophage therapy.
Adoptive cell therapy with chimeric antigen receptor (CAR) immunotherapy has made tremendous progress with five CAR T therapies approved by the US Food and Drug Administration for hematological malignancies. However, CAR immunotherapy in solid tumors lags significantly behind. Some of the major hurdles for CAR immunotherapy in solid tumors include CAR T cell manufacturing, lack of tumor-specific antigens, inefficient CAR T cell trafficking and infiltration into tumor sites, immunosuppressive tumor microenvironment (TME), therapy-associated toxicity, and antigen escape. CAR Natural Killer (NK) cells have several advantages over CAR T cells as the NK cells can be manufactured from pre-existing cell lines or allogeneic NK cells with unmatched major histocompatibility complex (MHC); can kill cancer cells through both CAR-dependent and CAR-independent pathways; and have less toxicity, especially cytokine-release syndrome and neurotoxicity. At least one clinical trial showed the efficacy and tolerability of CAR NK cell therapy. Macrophages can efficiently infiltrate into tumors, are major immune regulators and abundantly present in TME. The immunosuppressive M2 macrophages are at least as efficient as the proinflammatory M1 macrophages in phagocytosis of target cells; and M2 macrophages can be induced to differentiate to the M1 phenotype. Consequently, there is significant interest in developing CAR macrophages for cancer immunotherapy to overcome some major hurdles associated with CAR T/NK therapy, especially in solid tumors. Nevertheless, both CAR NK and CAR macrophages have their own limitations. This comprehensive review article will discuss the current status and the major hurdles associated with CAR T and CAR NK therapy, followed by the structure and cutting-edge research of developing CAR macrophages as cancer-specific phagocytes, antigen presenters, immunostimulators, and TME modifiers.


Accelerated, but not conventional, radiotherapy of murine B-cell lymphoma induces potent T cell-mediated remissions.
Conventional local tumor irradiation (LTI), delivered in small daily doses over several weeks, is used clinically as a palliative, rather than curative, treatment for chemotherapy-resistant diffuse large B-cell lymphoma (DLBCL) for patients who are ineligible for hematopoietic cell transplantation. Our goal was to test the hypothesis that accelerated, but not conventional, LTI would be more curative by inducing T cell-mediated durable remissions. We irradiated subcutaneous A20 and BL3750 lymphoma tumors in mice with a clinically relevant total radiation dose of 30 Gy LTI, delivered in 10 doses of 3 Gy over 4 days (accelerated irradiation) or as 10 doses of 3 Gy over 12 days (conventional irradiation). Compared with conventional LTI, accelerated LTI resulted in more complete and durable tumor remissions. The majority of these mice were resistant to rechallenge with lymphoma cells, demonstrating the induction of memory antitumor immunity. The increased efficacy of accelerated LTI correlated with higher levels of tumor cell necrosis vs apoptosis and expression of "immunogenic cell death" markers, including calreticulin, heat shock protein 70 (Hsp70), and Hsp90. Accelerated LTI-induced remissions were not seen in immunodeficient Rag-2 -/- mice, CD8+ T-cell-depleted mice, or Batf-3 -/- mice lacking CD8α+ and CD103+ dendritic cells. Accelerated, but not conventional, LTI in immunocompetent hosts induced marked increases in tumor-infiltrating CD4+ and CD8+ T cells and MHCII+CD103+CD11c+ dendritic cells and corresponding reductions in exhausted PD-1+Eomes+CD8+ T cells and CD4+CD25+FOXP3+ regulatory T cells. These findings raise the possibility that accelerated LTI can provide effective immune control of human DLBCL.


New models for the study of Mycobacterium-host interactions.
The outcome of Mycobacterium infection is determined by a series of complex interactions between the bacteria and host immunity. Traditionally, mammalian models and cultured cells have been used to study these interactions. Recently, ameba (Dictyostelium), fruit flies (Drosophila) and zebrafish, amenable to forward genetic screens, have been developed as models for mycobacterial pathogenesis. Infection of these hosts with mycobacteria has allowed the dissection of intracellular trafficking pathways (Dictyostelium) and the roles of phagocytic versus antimicrobial peptide responses (Drosophila). Real-time visualization of the optically transparent zebrafish embryo/larva has elucidated mechanisms by which Mycobacterium-infected leukocytes migrate and subsequently aggregate into granulomas, the hallmark pathological structures of tuberculosis.


Ferulic acid through mitigation of NMDA receptor pathway exerts anxiolytic-like effect in mouse model of maternal separation stress.
Background Experiencing early-life stress plays an important role in the pathophysiology of anxiety disorders. Ferulic acid is a phenolic compound found in some plants which has several pharmacological properties. N-methyl-D-aspartate (NMDA) receptors are involved in the pathophysiology of mood disorders. In this study we aimed to assess the anxiolytic-like effect of ferulic acid in a mouse model of maternal separation (MS) stress by focusing on the possible involvement of NMDA receptors. Methods Mice were treated with ferulic acid (5 and 40 mg/kg) alone and in combination with NMDA receptor agonist/antagonist. Valid behavioral tests were performed, including open field test (OFT) and elevated plus maze test (EPM), while quantitative real time polymerase chain reaction (qRT-PCR) was used to evaluate gene expression of NMDA subunits (GluN2A and GluN2B) in the hippocampus. Results Findings showed that treatment of MS mice with ferulic acid increased the time spent in the central zone of the OFT and increased both open arm time and the percent of open arm entries in the EPM. Ferulic acid reduced the expression of NMDA receptor subunit genes. We showed that administration of NMDA receptor agonist (NMDA) and antagonist (ketamine) exerted anxiogenic and anxiolytic-like effects, correspondingly. Results showed that co-administration of a sub-effective dose of ferulic acid plus ketamine potentiated the anxiolytic-like effect of ferulic acid. Furthermore, co-administration of an effective dose of ferulic acid plus NMDA receptor agonist (NMDA) attenuated the anxiolytic-like effect of ferulic acid. Conclusions In deduction, our findings showed that NMDA, partially at least, is involved in the anxiolytic-like effect of ferulic acid in the OFT and EPM tests.


[End-of-life care: experiences and expectations of bereaved relatives].
Within end-of-life care concepts, relatives of patients suffering from incurable illness are an important target group. This study aims to explore the experiences of relatives of deceased patients regarding health care delivery within the last days and weeks of life, and to work out implications for patient and relatives oriented improvement strategies. We conducted 19 qualitative interviews with bereaved relatives addressing the patient's use of health care services and satisfaction with the services, as well as communication and information. Interviews were transcribed verbatim and analyzed using qualitative content analysis. Three main categories were developed: (1) present health care delivery, e. g. positive and negative experiences concerning communication and information; (2) expectations and wishes, e. g. better support and coordination concerning discharge from hospital; (3) the relative and the dying patient, e. g. attitudes towards death and dying as well as individual limitations and resources. Overall, from the perspective of the bereaved relatives there are deficits concerning coordination of health care delivery and communication. Improving coordination of health care in particular with regard to the interfaces of outpatient and inpatient care, advanced care planning and strengthening "talking medicine" may contribute to optimize health care delivery for severely ill and dying patients and their relatives.


Decreased expression of miR-195 mediated by hypermethylation promotes osteosarcoma.
Osteosarcoma (OS) is the most common type of primary malignant bone tumor. The early lung metastasis of osteosarcoma is one of the main factors of poor prognosis. Therefore, searching for new targets and new mechanisms of osteosarcoma metastasis is essential for the prevention and treatment of osteosarcoma. Our previous studies suggested that fatty acid synthase (FASN) was an oncogene and promoted osteosarcoma. In addition, it is reported that the expression of miR-195 was negatively correlated with osteosarcoma. Aberrant DNA methylation can reversely regulate the expression of miRNAs. However, whether miR-195 could target FASN in osteosarcoma and whether ectopic DNA methylation is the upstream regulatory mechanism of miR-195 in metastasis of osteosarcoma are not fully studied. The expressions were detected by qPCR and western blot, and methylation level was determined by methylation-specific PCR. Luciferase reporter assay, MTT, wound healing, and Transwell assay were used. We found that the expression of miR-195 was low in osteosarcoma. The methylation of miR-195 was high. miR-195 targeted and decreased the expression of FASN. In osteosarcoma, miR-195 inhibited cell proliferation, cell migration, and invasion. The methylation of miR-195 was related to decreased miR-195, it might promote osteosarcoma.


Methylene-bridged bimetallic α-diimino nickel(II) complexes: synthesis and high efficiency in ethylene polymerization.
A series of 1,2-bis(arylimino)acenaphthylidenes (L1-L5) and their corresponding 4,4'-methylenebis(1-(2,6-diisopropylphenylimino)-2-(arylimino)acenaphthylene) derivatives (L6-L10) were synthesized and used to form mono-nuclear nickel bromides LnNiBr2 (n = 1-5, Ni1-Ni5) and bi-nuclear nickel halides LnNi2X4 (n = 6-10: X = Br, Ni2-1-Ni2-5; n = 4, X = Cl, Ni2-6). All the organic compounds were fully characterized by FT-IR spectra, NMR measurements and elemental analysis. The nickel complexes were characterized by FT-IR spectra and elemental analysis and the molecular structures of the representative complexes Ni1, Ni2-1 and Ni2-3 were confirmed by single-crystal X-ray diffraction. Upon activation with either Et2AlCl or MAO, all the nickel complex pre-catalysts exhibited high activity toward ethylene polymerization over the temperature range from ambient to 50 °C. In general, the bi-nuclear complexes showed a positive synergetic effect with higher activity than their mono nuclear analogs. The resultant polyethylene possessed higher molecular weight and a high degree of branching.


Kynurenic Acid Inhibits the Electrical Stimulation Induced Elevated Pituitary Adenylate Cyclase-Activating Polypeptide Expression in the TNC.
Migraine is a primary headache of imprecisely known mechanism, but activation of the trigeminovascular system (TS) appears to be essential during the attack. Intensive research has recently focused on pituitary adenylate cyclase-activating polypeptide (PACAP) and the kynurenine systems as potential pathogenic factors. We investigated the link between these important mediators and the effects of kynurenic acid (KYNA) and its synthetic analog (KYNA-a) on PACAP expression in the rat trigeminal nucleus caudalis (TNC) in a TS stimulation model related to migraine mechanisms. Adult male Sprague-Dawley rats were pretreated with KYNA, KYNA-a, the NMDA receptor antagonist MK-801, or saline (vehicle). Next, the trigeminal ganglion (TRG) was electrically stimulated, the animals were transcardially perfused following 180 min, and the TNC was removed. In the TNC samples, 38 amino acid form of PACAP (PACAP1-38)-like radioimmunoactivity was measured by radioimmunoassay, the relative optical density of preproPACAP was assessed by Western blot analysis, and PACAP1-38 mRNA was detected by real-time PCR. Electrical TRG stimulation resulted in significant increases of PACAP1-38-LI, preproPACAP, and PACAP1-38 mRNA in the TNC. These increases were prevented by the pretreatments with KYNA, KYNA-a, and MK-801. This is the first study to provide evidence for a direct link between PACAP and the kynurenine system during TS activation.


The binding of complementary oligoribonucleotides to yeast initiator Transfer RNA.
Oligoribonucleotide binding to baker's yeast initiator tRNA was measured by equilibrium dialysis in order to determine which regions of the tRNA were free to bind complementary oligomers and which were involved in secondary and tertiary structure. Association constants of trinucleoside diphosphates and tetranucleoside triphophates complementary to the single-stranded regions of the cloverleaf structure of yeast tRNAfMet were measured at o degrees in 1.0 M NaCl, and 0.01 M MgCl2. The only regions of the tRNA whose complementary oligomers bound to the tRNA were the amino acid acceptor end and the five nucleotides at the 5' end of the anticodon loop. These results differ from those for the other tRNAs studied by this technique; usually oligomers complementary to the dihydrouracil loop bind to the tRNA. The sequence of yeast tRNAfMet and other eucaryotic initiators is unusual. The "TpsiC loop" contains the sequence A-U-C instead of T-psi-C, yet the binding pattern to the THE TpsiC LOOP IS LIKE THAT FOR OTHER TRNAs; no oligomers bind.


Genotypes of rubella virus and the epidemiology of rubella infections in the Democratic Republic of the Congo, 2004-2013.
Rubella is a viral infection that may cause fetal death or congenital defects, known as congenital rubella syndrome (CRS), during early pregnancy. The World Health Organization (WHO) recommends that countries assess the burden of rubella and CRS, including the determination of genotypes of circulating viruses. The goal of this study was to identify the genotypes of rubella viruses in the Democratic Republic of the Congo (DRC). Serum or throat swab samples were collected through the measles surveillance system. Sera that tested negative for measles IgM antibody were tested for rubella IgM antibody. Serum collected within 4 days of rash onset and throat swabs were screened by real-time RT-PCR for rubella virus RNA. For positive samples, an amplicon of the E1 glycoprotein gene was amplified by RT-PCR and sequenced. 11733 sera were tested for rubella IgM and 2816 (24%) were positive; 145 (5%) were tested for the presence of rubella RNA by real-time RT-PCR and 10 (7%) were positive. Seventeen throat swabs were analyzed by RT-PCR and three were positive. Sequences were obtained from eight of the positive samples. Phylogenetic analysis showed that the DRC rubella viruses belonged to genotypes 1B, 1E, 1G, and 2B. This report provides the first information on the genotypes of rubella virus circulating in the DRC. These data contribute to a better understanding of rubella burden and the dynamics of rubella virus circulation in Africa. Efforts to establish rubella surveillance in the DRC are needed to support rubella elimination in Africa. J. Med. Virol. 88:1677-1684, 2016. © 2016 Wiley Periodicals, Inc.


Gilded and gelded. Hard-won lessons from the PR wars.
A golden statue of a winged youth once perched on the roof of AT&T's old headquarters. But when AT&T lowered the 24-foot-high statue for regilding so that it could be placed in the company's new headquarters, the chairman was shocked to discover that the figure was anatomically correct. So he decreed that it also be gelded. The altered "Golden Boy" thus became a metaphor for AT&T's recent embattled history, and it serves as a cautionary symbol for all companies operating in today's brutal business environment, where perception can be as important as reality. While image consultants and executives work to gild a company's image, special interest groups and the media can geld a company with countless little cuts. The author, a former executive vice president of public relations for AT&T, provides an insider's view of some of the company's most painful public-relations scrapes. They include the collapse of two apparent CEO succession plans, AT&T's inability to meet heightened expectations after Mike Armstrong was appointed CEO, and the racially charged furor over a cartoon in an employee publication. The author offers four lessons: Don't become hypnotized by your own buzz; understand the way the business media think; address the needs of all your stakeholders; and be sensitive to the possible emotional resonance of what appear to be straightforward facts. To illustrate the final point, the author mentions AT&T's elimination of 40,000 jobs in 1996. Wall Street was impressed, but NBC's Tom Brokaw said the workforce reduction might signal "another long, anxious year for the American middle class." No rational argument from AT&T could overcome the layoffs' symbolic impact. Wounded but wiser after numerous public-relations battles, the company eventually learned to stop aggregating job-reduction information for the media.


Publisher Correction: Observation of photobleaching in Ge-deficient Ge16.8Se83.2 chalcogenide thin film with prolonged irradiation.
A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.


Fundamentals of FGF19 & FGF21 action in vitro and in vivo.
Fibroblast growth factors 19 (FGF19) and 21 (FGF21) have emerged as key regulators of energy metabolism. Several studies have been conducted to understand the mechanism of FGF19 and FGF21 action, however, the data presented has often been inconsistent and at times contradictory. Here in a single study we compare the mechanisms mediating FGF19/FGF21 actions, and how similarities/differences in actions at the cellular level between these two factors translate to common/divergent physiological outputs. Firstly, we show that in cell culture FGF19/FGF21 are very similar, however, key differences are still observed differentiating the two. In vitro we found that both FGF's activate FGFRs in the context of βKlotho (KLB) expression. Furthermore, both factors alter ERK phosphorylation and glucose uptake with comparable potency. Combination treatment of cells with both factors did not have additive effects and treatment with a competitive inhibitor, the FGF21 delta N17 mutant, also blocked FGF19's effects, suggestive of a shared receptor activation mechanism. The key differences between FGF21/FGF19 were noted at the receptor interaction level, specifically the unique ability of FGF19 to bind/signal directly via FGFR4. To determine if differential effects on energy homeostasis and hepatic mitogenicity exist we treated DIO and ob/ob mice with FGF19/FGF21. We find comparable efficacy of the two proteins to correct body weight and serum glucose in both DIO and ob/ob mice. Nevertheless, FGF21 and FGF19 had distinctly different effects on proliferation in the liver. Interestingly, in vivo blockade of FGF21 signaling in mice using ΔN17 caused profound changes in glycemia indicative of the critical role KLB and FGF21 play in the regulation of glucose homeostasis. Overall, our data demonstrate that while subtle differences exist in vitro the metabolic effects in vivo of FGF19/FGF21 are indistinguishable, supporting a shared mechanism of action for these two hormones in the regulation of energy balance.


Osmolytes induce structure in an early intermediate on the folding pathway of barstar.
Osmolytes stabilize proteins against denaturation, but little is known about how their stabilizing effect might affect a protein folding pathway. Here, we report the effects of the osmolytes, trimethylamine-N-oxide, and sarcosine on the stability of the native state of barstar as well as on the structural heterogeneity of an early intermediate ensemble, IE, on its folding pathway. Both osmolytes increase the stability of the native protein to a similar extent, with stability increasing linearly with osmolyte concentration. Both osmolytes also increase the stability of IE but to different extents. Such stabilization leads to an acceleration in the folding rate. Both osmolytes also alter the structure of IE but do so differentially; the fluorescence and circular dichroism properties of IE differ in the presence of the different osmolytes. Because these properties also differ from those of the unfolded form in refolding conditions, different burst phase changes in the optical signals are seen for folding in the presence of the different osmolytes. An analysis of the urea dependence of the burst phase changes in fluorescence and circular dichroism demonstrates that the formation of IE is itself a multistep process during folding and that the two osmolytes act by stabilizing, differentially, different structural components present in the IE ensemble. Thus, osmolytes can alter the basic nature of a protein folding pathway by discriminating, through differential stabilization, between different members of an early intermediate ensemble, and in doing so, they thereby appear to channel folding along one route when many routes are available.


Mechanistic and evolutionary insights into a type V-M CRISPR-Cas effector enzyme.
RNA-guided type V CRISPR-Cas12 effectors provide adaptive immunity against mobile genetic elements (MGEs) in bacteria and archaea. Among diverse Cas12 enzymes, the recently identified Cas12m2 (CRISPR-Cas type V-M) is highly compact and has a unique RuvC active site. Although the non-canonical RuvC triad does not permit dsDNA cleavage, Cas12m2 still protects against invading MGEs through transcriptional silencing by strong DNA binding. However, the molecular mechanism of RNA-guided genome inactivation by Cas12m2 remains unknown. Here we report cryo-electron microscopy structures of two states of Cas12m2-CRISPR RNA (crRNA)-target DNA ternary complexes and the Cas12m2-crRNA binary complex, revealing structural dynamics during crRNA-target DNA heteroduplex formation. The structures indicate that the non-target DNA strand is tightly bound to a unique arginine-rich cluster in the recognition (REC) domains and the non-canonical active site in the RuvC domain, ensuring strong DNA-binding affinity of Cas12m2. Furthermore, a structural comparison of Cas12m2 with TnpB, a putative ancestor of Cas12 enzymes, suggests that the interaction of the characteristic coiled-coil REC2 insertion with the protospacer-adjacent motif-distal region of the heteroduplex is crucial for Cas12m2 to engage in adaptive immunity. Collectively, our findings improve mechanistic understanding of diverse type V CRISPR-Cas effectors and provide insights into the evolution of TnpB to Cas12 enzymes.


Premaxillary distraction osteogenesis with an individual tooth-borne appliance.
Distraction osteogenesis defines a technique of bone generation and osteosynthesis by the distraction of native preexisting bone. The technique offers a promising treatment alternative for patients with maxillary hypoplasia and a retrognathic mandible. In this case report, the steps in the treatment of an 18.2-year-old girl with premaxillary hypoplasia and anterior crossbite are described. The patient was treated with a distraction osteogenesis technique, and premaxillary advancement was performed using an individual tooth-borne distraction device. The surgical operation consisted of a classical segmental maxillary osteotomy carefully respecting the palatal periosteum. The distractor was cemented in the mouth after the surgical procedures. The patient was observed during a seven-day latency period, after which the device was activated 0.5 mm every 12 hours. The anterior crossbite was eliminated in one week, and the treatment was finished with fixed orthodontic appliances.


Targeting of captopril to the kidney reduces renal angiotensin-converting enzyme activity without affecting systemic blood pressure.
We have synthesized a prodrug of the angiotensin-converting enzyme (ACE) inhibitor captopril by coupling this drug covalently to the low molecular weight protein (LMWP) lysozyme. Such drug-LMWP conjugates can be used for renal drug delivery, since LMWPs accumulate specifically in the proximal tubular cells of the kidney. In the present study, we compared the effects of captopril-lysozyme and free captopril in male Wistar rats. ACE activity in plasma and the kidney was measured after intravenous bolus injection of either the captopril-lysozyme conjugate (33 mg. kg(-1), corresponding to 0.2 mg. kg(-1) captopril) or equivalent dosages of free captopril and lysozyme. The administration of the captopril-lysozyme conjugate resulted in less plasma ACE inhibition and a longer-lasting renal ACE inhibition compared with the free drug. Effects on blood pressure and natriuresis were studied during intravenous infusion of captopril-lysozyme (275 mg. kg(-1). 6 h(-1) conjugate, corresponding to 5 mg. kg(-1). 6 h(-1) captopril) or an equimolar dosage of free captopril. Captopril-lysozyme did not affect systemic blood pressure, whereas free captopril lowered blood pressure significantly (-23 +/- 32% versus control after 6 h). Captopril-lysozyme increased natriuresis about 3-fold compared with control levels (260 +/- 32% after 6 h), whereas free captopril treatment resulted in a reduced sodium excretion (26 +/- 12%). Furthermore, captopril at a lower dose, which only moderately lowered blood pressure, showed an increased sodium excretion. We conclude that renal delivery of captopril using captopril-lysozyme results in reduced systemic activity and increased kidney-specific activity of the targeted drug.


High integrity interconnection of silver submicron/nanoparticles on silicon wafer by femtosecond laser irradiation.
Welding of nanomaterials is a promising technique for constructing nanodevices with robust mechanical properties. To date, fabrication of these devices is limited because of difficulties in restricting damage to the nanomaterials during the welding process. In this work, by utilizing very low fluence (∼900 μJ cm(-2)) femtosecond (fs) laser irradiation, we have produced a metallic interconnection between two adjacent silver (Ag) submicron/nanoparticles which were fixed on a silicon (Si) wafer after fs laser deposition. No additional filler material was used, and the connected particles remain almost damage free. Observation of the morphology before and after joining and finite difference time domain simulations indicate that the interconnection can be attributed to plasmonic excitation in the Ag submicron/nanoparticles. Concentration of energy between the particles leads to local ablation followed by re-deposition of the ablated material to form a bridging link that joins the two particles. This welding technique shows potential applications in the fabrication of nanodevices.


Pleiotropic Chemotherapy to Abrogate Glioblastoma Multiforme Migration/Invasion.
Current clinical failure to cure primary glioblastoma multiforme in virtually all adult patients is due to genetic aberrations, molecular heterogeneity, and clonal evolution of tumor stem and differentiated cells within the core tumor, leading to their migration, invasion and proliferation in normal surrounding and in distant cerebral tissue sites. These factors are the causes of targeted drug resistance, inadequate surgical removal, and inadequate radio-therapeutic interventions. Resolution of this clinical conundrum may be found in administration of Withaferin A alone or in combination with pleiotropic drugs which address aberrant molecules and pathways promoting tumor cell motility, migration, invasion and proliferation.


Dibenz[b,f]oxepin and Antimycobacterial Chalcone Constituents of Empetrum nigrum.
Two new dibenz[b,f]oxepins, empetroxepins A and B (1 and 2), and seven known compounds (3-9) were isolated from an extract of the Canadian medicinal plant Empetrum nigrum that significantly inhibited the growth of Mycobacterium tuberculosis H37Ra. The structures of 1 and 2 were established through analysis of NMR and MS data. The antimycobacterial activity of the plant extract was attributed primarily to the presence of two chalcone derivatives (6 and 7) that exhibited selective antimycobacterial activity (IC50 values of 23.8 and 32.8 μM, respectively) in comparison to mammalian (HEK 293) cells (IC50 values of 109 and 249 μM, respectively).


The possible role of contact sensitization to fragrances and preservatives in poikiloderma of civatte.
Numerous mechanisms have been postulated to play an important role in the pathogenesis of poikiloderma of Civatte (PC), including chronic exposure to ultraviolet radiation, menopause-related hormonal changes, contact hypersensitivity and genetic predisposition. Herein, we report a case of contact sensitization to fragrances and commonly used preservatives, methylchloroisothiazolinone and methylisothiazolinone, also widely known as Kathon CG, in a post-menopausal woman with PC, who denied excessive sun exposure and a family history. After abstaining from the use of her personal care products containing the documented allergens, not only the itching and burning symptoms, but also the cutaneous changes appeared to improve partially. This report underlines the possible influence of contact hypersensitivity in the pathogenesis of PC.


Prevalence of restless leg syndrome in subjects with depressive disorder.
Restless legs syndrome (RLS) is known to be associated with depression. We hypothesized that RLS in depression is linked to the severity, duration, and frequency of depressive episodes. Subjects fulfilling DSM-IV-TR criteria of depressive disorders were included in this study after seeking informed consent. Using structured interview of MINI-Plus their demographic data and history were recorded. Severity of depression was assessed with the help of HAM-D. Insomnia was diagnosed following ICSD-2 criteria. RLS was diagnosed according to IRLSSG criteria. Descriptive statistics, Chi-square test, independent sample t test and MANOVA were computed with the help of SPSS v 17.0. RLS was reported by 31.48% of sample. There was no gender difference in prevalence of RLS (X(2) =0.46; P=0.33). There was no difference in the age , total duration of depressive illness and number of depressive episodes between RLS and non-RLS groups (F=0.44; P=0.77; Wilk's Lambda=0.96). The HAM-D score was higher in the non-RLS group (P=0.03). Onset of RLS symptoms was not related to onset of depressive symptoms. RLS is prevalent in depressive disorder. However, onset of RLS is unrelated to age and number or duration of depressive disorders.


Fluorescence contributions of the individual Trp residues in goat alpha-lactalbumin.
Goat alpha-lactalbumin (GLA) contains four tryptophan (Trp) residues. In order to obtain information on the fluorescence contribution of the individual Trp residues in native GLA, we recorded the fluorescence spectra of four GLA mutants, W26F, W60F, W104F, and W118F, in each of which a single Trp residue was replaced with phenylalanine (Phe). Comparison of the fluorescence spectra of the four mutants with that of wild-type GLA indicated that, in native GLA, three Trp residues (Trp60, Trp104, and Trp118) are strongly quenched and account for the partial indirect quenching of Trp26. As a consequence, the fluorescence of wild-type GLA and of the mutants W60F, W104F, and W118F mainly results from Trp26. An inspection of the crystal structure indicated that, in addition to the disulfide bonds that are in direct contact with the indole groups of Trp60 and Trp118, backbone peptide bonds that are in direct contact with the indole groups of Trp60, Trp104, and Trp118, contribute to the direct quenching effects. Interestingly, the lack of direct quenching of Trp26 explains why the cleavage of disulfide bonds by UV light is mediated more by the highly fluorescent Trp26 than by the less fluorescent Trp104 and Trp118.


Avoidance and confrontation of painful, back-straining movements in chronic back pain patients.
Avoidance of painful activities has been proposed to be an important risk factor for the initiation and maintenance of chronic low back suffering, whereas exposure to these activities has been suggested to be beneficial for recovery. In a cross-sectional study, the differences between chronic patients with avoidant and confrontational styles were investigated using self-report measures and a behavioral test. Participants were first classified as avoiders or confronters. In comparison with confronters, avoiders reported greater frequency and duration of pain, higher fear of pain and injury, more disability in daily living, and more attention to back sensations. Finally, avoiders reported more fear of (re)injury during the behavioral test and had a worse performance than confronters. The results suggest a close link between the fear of pain/(re)injury on one hand and avoidance behavior and physical deconditioning on the other hand.


Alleviation of hyperglycemia in diabetic rats by intraportal injection of insulin-producing cells generated from surgically resected human pancreatic tissue.
Although islet transplantation holds promise for the treatment of diabetes, the scarcity of donor tissue remains a major drawback. The aim of this study is to generate insulin-producing cells from adult human pancreatic cells isolated from surgically resected pancreatic tissue. To isolate pancreatic endocrine precursor cells from 57 surgically resected pancreases, the cells were cultured and propagated in conditioned medium after which they were differentiated in Matrigel. The resultant cells were characterized using morphology, immunofluorescent studies, expression of differentiated pancreatic islet-specific genes using quantitative reverse transcription-PCR, and glucose-induced insulin secretion through analysis of C-peptide secretion. The relationships between propagation of insulin-producing cells and clinical variables of the donor were also analyzed. Finally, insulin-producing cell function was examined in streptozotocin-induced diabetic rats. Pancreatic endocrine precursor cells were successfully cultured; insulin-producing cells cultured from soft pancreas parenchyma had a significantly higher success rate. Morphological examination revealed islet-like cluster formation upon transfer to Matrigel. The presence of the neural stem cell marker nestin, duct cell marker cytokeratin 19, and endocrine cell markers C-peptide and pancreatic and duodenal homeobox 1, was also observed. In addition, glucose-stimulated C-peptide release was significantly increased in the insulin-producing cells. Furthermore, in diabetic rats, transplantation of insulin-producing cells reduced hyperglycemia. Isolated pancreatic endocrine precursor cells from surgically resected pancreatic tissue differentiated into insulin-producing cells and showed characteristics of functional endocrine cells. Thus, surgically resected pancreatic tissue may represent an alternative source of functional insulin-producing cells.


Initiation of Escherichia coli minichromosome replication at oriC and at protein n' recognition sites. Two modes for initiating DNA synthesis in vitro.
The start sites for leading and lagging DNA strands were determined in vitro with minichromosomes as templates. Fragments from replication intermediates were analyzed by hybridization to single-stranded probes. Leading strand synthesis in the counterclockwise direction was found to originate in or close to (position 248 to -44) the minimal origin. Complementary lagging strand synthesis started several positions to the left outside of oriC. The results suggest in addition a concerted synthesis of leading and lagging strands following the dnaA directed assembly of initiation proteins at double-stranded oricC DNA (pre-replisome). In addition, DNA synthesis could initiate at protein n' recognition sequences located within and clockwise to the asnA gene. Initiation at n' sites was dependent on protein i activity, whereas leading and lagging strand initiation in the oriC region was not affected by protein i. Our results argue against an involvement of the phi X174-type primosome in the initiation of discontinuous DNA synthesis at oriC. An alternative function is suggested.


[Role of polymorphonucleocyte-produced leukotriene B4 in Kawasaki disease].
It is postulated that inflammatory cells play an important role in the process of developing vasculitis in Kawasaki Disease. LTB4, a 5-lipoxygenase product of arachidonic acid is one of the most potent chemoattractants to inflammatory cells and is produced in large amounts by PMNs. We investigated the role of PMN-derived LTB4 in Kawasaki Disease. Isolated PMNs were obtained from 19 Kawasaki disease patients in three different phases of the illness, (acute phase: 0-12th day, convalescent phase: 13-29th day, restored phase: greater than 30th day). LTB4 synthesis in the convalescent phase was 26.43 +/- 4.2 ng/5 x 10(6) cells, which was significantly higher than those in the acute and restored phases (11.90 +/- 1.91, 13.87 +/- 1.86 ng) and also higher than that in the control subjects (10.65 +/- 1.26 ng: p less than 0.05). No differences were found between two groups with or without coronary lesions. The results imply that activated PMNs during the convalescent phase of illness produce larger amount of LTB4 which may participate in the development of inflammatory process of the disease and that PMN-derived LTB4 plays no significant roles in the development of coronary lesions.


IR signature of the photoionization-induced hydrophobic-->hydrophilic site switching in phenol-Arn clusters.
IR spectra of phenol-Arn (PhOH-Arn) clusters with n=1 and 2 were measured in the neutral and cationic electronic ground states in order to determine the preferential intermolecular ligand binding motifs, hydrogen bonding (hydrophilic interaction) versus pi bonding (hydrophobic interaction). Analysis of the vibrational frequencies of the OH stretching motion, nuOH, observed in nanosecond IR spectra demonstrates that neutral PhOH-Ar and PhOH-Ar2 as well as cationic PhOH+-Ar have a pi-bound structure, in which the Ar atoms bind to the aromatic ring. In contrast, the PhOH+-Ar2 cluster cation is concluded to have a H-bound structure, in which one Ar atom is hydrogen-bonded to the OH group. This pi-->H binding site switching induced by ionization was directly monitored in real time by picosecond time-resolved IR spectroscopy. The pi-bound nuOH band is observed just after the ionization and disappears simultaneously with the appearance of the H-bound nuOH band. The analysis of the picosecond IR spectra demonstrates that (i) the pi-->H site switching is an elementary reaction with a time constant of approximately 7 ps, which is roughly independent of the available internal vibrational energy, (ii) the barrier for the isomerization reaction is rather low(<100 cm(-1)), (iii) both the position and the width of the H-bound nuOH band change with the delay time, and the time evolution of these spectral changes can be rationalized by intracluster vibrational energy redistribution occurring after the site switching. The observation of the ionization-induced switch from pi bonding to H bonding in the PhOH+-Ar2 cation corresponds to the first manifestation of an intermolecular isomerization reaction in a charged aggregate.


Integration of Cell-Penetrating Peptides with Rod-like Bionanoparticles: Virus-Inspired Gene-Silencing Technology.
Inspired by the high gene transfer efficiency of viral vectors and to avoid side effects, we present here a 1D rod-like gene-silencing vector based on a plant virus. By decorating the transacting activator of transduction (TAT) peptide on the exterior surface, the TAT-modified tobacco mosaic virus (TMV) achieves a tunable isoelectric point (from ∼3.5 to ∼9.6) depending on the TAT dose. In addition to enhanced cell internalization, this plant virus-based vector (TMV-TAT) acquired endo/lysosomal escape capacity without inducing lysosomal damage, resulting in both high efficiency and low cytotoxicity. By loading silencer green fluorescent protein (GFP) siRNA onto the TMV-TAT vector (siRNA@TMV-TAT) and interfering with GFP-expressing mouse epidermal stem cells (ESCs/GFP) in vitro, the proportion of GFP-positive cells could be knocked down to levels even lower than 15% at a concentration of ∼100% cell viability. Moreover, by interfering with GFP-expressing highly metastatic hepatocellular carcinoma (MHCC97-H/GFP) tumors in vivo, treatment with siRNA@TMV-TAT complexes for 10 days achieved a GFP-negative rate as high as 80.8%. This work combines the high efficiency of viral vectors and the safety of nonviral vectors and may provide a promising strategy for gene-silencing technology.


[Chronic obstructive pulmonary disease patients undergoing home oxygen therapy: a study of clinical parameters, nutritional status and ambulatory capacity].
The aim of the study was to document the nutritional status and the calorie demands of patients suffering from severe chronic airflow obstruction (BPCO) who were on continuous domiciliary oxygen therapy (OCD) and to correlate this information with the clinical picture, the severity of the respiratory disease and the daily distance walked, this to be measured in a prospective manner. Fifty clinically stable patients with chronic airflow obstruction on continuous oxygen therapy for 33 months (range 4-106) in whom the following measures were made at home: pulmonary function, maximal static inspiratory and expiratory pressure (PIMAX and PEMAX), strength of hand, grip, the mean distance walked daily (wearing a pedometer for one week), body mass index (IMC), and the body composition by electrical bio-impedence and calorie requirements. Thirty four per cent of patients presented with an excessive body mass (IMC > 27 kg/m2), 42 per cent had normal nutrition (IMC 20-27 kg/m2) and 24 per cent were malnourished (IMC < 20 kg/m2). Malnourished patients had, in a statistically significant manner, airflow obstruction of greater severity and a lower oxygen saturation and a PEMAX as well as a lower daily distance compared to over weight subjects. However, their net calorie requirements were markedly higher (39 +/- 5 Kcal/kg/j) compared to patients having normal weight (29 +/- 11 kcal/kg/j) or excess weight (25 +/- 8 kcal/kg/j). From the clinical standpoint no malnourished patient fulfilled the clinical criteria of chronic bronchitis. By contrast 61 per cent of subjects with normal nutrition and 94 per cent of subjects with excessive weight were chronic bronchitics. In the group of patients with severe airflow obstruction on domiciliary oxygen, 25 per cent were malnourished and this was in spite of netly increased calorie consumption which is superior to their theoretical need. This suggests that the solution of increasing supplements to their dietary requirements would be a difficult to realise. These subjects presented also with a more marked ventilatory handicap and a clinical picture characterised by the absence of the classical signs of chronic bronchitis.


Fast response and high sensitivity europium metal organic framework fluorescent probe with chelating terpyridine sites for Fe³⁺.
Iron is one of the most important elements in the metabolic process for all living system. However, both its deficiency and excess from normal permissible limits can induce serious disorders. We synthesized a europium-based metal-organic framework (Eu-MOF), EuL(3) (L = 4'-(4-carboxyphenyl)-2,2': 6',2″-terpyridine), under hydrothermal conditions, and used it as a solid luminescence sensor for Fe(3+) ions. The robust EuL(3) shows fast response (∼ 1 min) and high sensitivity (Stern-Volmer constant K(SV) = 4.1 × 10(3) L/mol) for Fe(3+) ions in aqueous solution or biological systems due to the existence of chelating terpyridine and open channels. The simple and portable test paper based on the EuL(3) fluorescent sensor system provides a convenient and reliable detection of Fe(3+) in every day applications. This pioneering work contributes to extend the potential application of Ln-MOFs to the biological and environmental areas.


Voltage-gated Ca2+ entry and ryanodine receptor Ca2+-induced Ca2+ release in preglomerular arterioles.
We have previously shown that in afferent arterioles, angiotensin II (ANG II) involves activation of the inositol trisphosphate receptor (IP(3)R), activation of adenine diphosphoribose (ADPR) cyclase, and amplification of the initial IP(3)R-stimulated release of cytosolic Ca(2+) ([Ca(2+)](i)) from the sarcoplasmic reticulum (SR) (Fellner SK, Arendshorst WJ. Am J Physiol Renal Physiol 288: F785-F791, 2004). The response of the ryanodine receptor (RyR) to local increases in [Ca(2+)](i) is defined as calcium-induced calcium release (CICR). To investigate whether Ca(2+) entry via voltage-gated channels (VGCC) can stimulate CICR, we treated fura 2-loaded, freshly isolated afferent arterioles with KCl (40 mM; high KCl). In control arterioles, peak [Ca(2+)](i) increased by 165 +/- 10 nM. Locking the RyR in the closed position with ryanodine (100 microM) inhibited the [Ca(2+)](i) response by 59% (P < 0.01). 8-Br cADPR, a specific blocker of the ability of cyclic ADPR (cADPR) to sensitize the RyR to Ca(2+), caused a 43% inhibition. We suggest that the lower inhibition by 8-Br cADPR (P = 0.02, ryanodine vs. 8-Br cADPR) represents endogenously active ADPR cyclase. Depletion of SR Ca(2+) stores by inhibiting the SR Ca(2+)-ATPase with cyclopiazonic acid or thapsigargin blocked the [Ca(2+)](i) responses to KCl by 51% (P not significant vs. ryanodine or 8-Br cADPR). These data suggest that about half of the increase in [Ca(2+)](i) induced by high KCl is accomplished by activation of CICR through the ability of entered Ca(2+) to expose the RyR to high local concentrations of Ca(2+) and that endogenous cADPR contributes to the process.


Immunodeficiency in leprosy.
It is known that the impairment of cell-mediated immunity (CM) exists in lepromatous leprosy patients. This was shown by 1) delayed skin reaction to various test antigens, 2) decreased transformation of lymphocytes by various antigens, 3) delayed rejection of skin allograft, 4) decreased migration inhibitory fa-tor (MIF) formation, and 5) histologic study of the lymph node. In addition to these previous works, we have studied T and B lymphocytes in peripheral blood of leprosy patients; T cells by the technic of rosette formation, and B cells by staining surface immunoglobulins. The result of our study shows decreased numbers of T cells and increased numbers of B cells in peripheral blood of lepromatous patients. A the same time, we found that allogenic leukocyte infusion treatment reversed T and B-cell abnormalities. We know that repeated infusions of allogenic leukocytes dramatically brought about improvement of the clinical status of the patients, resolution of skin lesions, subsidence of erythema nodosum leprosum reaction, clearance of bacteria from the skin and lymph nodes, and reconstitution of peripheral lymph nodes.


Intracranial volume in 15 children with bilateral coronal craniosynostosis.
Intracranial volume (ICV) growth in patients with bilateral coronal craniosynostosis (BCS) is not well described. It is therefore important to evaluate the consequences of cranial surgery in children with this condition. The aim of the present study was to evaluate ICVs in patients operated on for BCS. A consecutive series of patients with BCS were operated on using spring-assisted cranioplasty, with computed tomography scans in 0.6-mm slices, were included. A MATLAB-based computer program capable of measuring ICV was used. Patients were compared with an age- and gender-matched control group of healthy children. Student's t test was used for statistical analysis. Fifteen patients (7 girls and 8 boys) with 43 computed tomography scans were identified. The diagnoses were 13 syndromic BCS (3 Apert, 1 Crouzon, 6 Muenke, and 3 Saethre-Chotzen) and 2 nonsyndromic BCS. The mean preoperative volume at the age of 5 months (n = 15) was 887 mL (range, 687-1082). Mean volume at follow-up at the age of 3 years (n = 13) was 1369 mL (range, 1196-1616). In comparison, the mean ICVs for controls at the ages of 5 months (n = 30) and 3 years (n = 26) were 854 mL and 1358 mL, respectively. The differences were not statistically significant (P > 0.05). Patients with BCS were operated on with spring-assisted cranioplasty seem to maintain their age-related ICV at 3 years of age when compared to normal children.


Toll-like receptor 2 plays a critical role in maintaining mucosal integrity during Citrobacter rodentium-induced colitis.
Inflammatory bowel diseases and infectious gastroenteritis likely occur when the integrity of intestinal barriers is disrupted allowing luminal bacterial products to cross into the intestinal mucosa, stimulating immune cells and triggering inflammation. While specific Toll-like receptors (TLR) are involved in the generation of inflammatory responses against enteric bacteria, their contributions to the maintenance of intestinal mucosal integrity are less clear. These studies investigated the role of TLR2 in a model of murine colitis induced by the bacterial pathogen Citrobacter rodentium. C. rodentium supernatants specifically activated TLR2 in vitro while infected TLR2-/- mice suffered a lethal colitis coincident with colonic mucosal ulcerations, bleeding and increased cell death but not increased pathogen burden. TLR2-/- mice suffered impaired epithelial barrier function mediated via zonula occludens (ZO)-1 in naïve mice and claudin-3 in infected mice, suggesting this could underlie their susceptibility. TLR2 deficiency was also associated with impaired production of IL-6 by bone marrow-derived macrophages and infected colons cultured ex vivo. As IL-6 has antiapoptotic and epithelial repair capabilities, its reduced expression could contribute to the impaired mucosal integrity. These studies report for the first time that TLR2 plays a critical role in maintaining intestinal mucosal integrity during infection by a bacterial pathogen.


Context-dependent host dispersal and habitat fragmentation determine heterogeneity in infected tick burdens: an agent-based modelling study.
As the incidence of tick-borne diseases has sharply increased over the past decade, with serious consequences for human and animal health, there is a need to identify ecological drivers contributing to heterogeneity in tick-borne disease risk. In particular, the relative importance of animal host dispersal behaviour in its three context-dependent phases of emigration, transfer and settlement is relatively unexplored. We built a spatially explicit agent-based model to investigate how the host dispersal process, in concert with the tick and host demographic processes, habitat fragmentation and the pathogen transmission process, affects infected tick distributions among hosts. A sensitivity analysis explored the impacts of different input parameters on infected tick burdens on hosts and infected tick distributions among hosts. Our simulations indicate that ecological predictors of infected tick burdens differed among the post-egg life stages of ticks, with tick attachment and detachment, tick questing activity and pathogen transmission dynamics identified as key processes, in a coherent way. We also found that the type of host settlement strategy and the proportion of habitat suitable for hosts determined super-spreading of infected ticks. We developed a theoretical mechanistic framework that can serve as a first step towards applied studies of on-the-ground public health intervention strategies.


Public Preferences for Social Distancing Policy Measures to Mitigate the Spread of COVID-19 in Missouri.
Policies to promote social distancing can minimize COVID-19 transmission but come with substantial social and economic costs. Quantifying relative preferences among the public for such practices can inform locally relevant policy prioritization and optimize uptake. To evaluate relative utilities (ie, preferences) for COVID-19 pandemic social distancing strategies against the hypothetical risk of acquiring COVID-19 and anticipated income loss. This survey study recruited individuals living in the Missouri area from May to June 2020 via randomly distributed unincentivized social media advertisements and local recruitment platforms for members of minority racial and ethnic groups. Participants answered 6 questions that asked them to choose between 2 hypothetical counties where business closures, social distancing policy duration, COVID-19 infection risk, and income loss varied. Reweighted population-level relative preferences (utilities) for social distancing policies, subgroups, and latent classes. The survey had a 3% response rate (3045 of 90 320). Of the 2428 respondents who completed the survey, 1669 (75%) were 35 years and older, 1536 (69%) were women, and 1973 (89%) were White. After reweighting to match Missouri population demographic characteristics, the strongest preference was for the prohibition of large gatherings (mean preference, -1.43; 95% CI, -1.67 to -1.18), with relative indifference to the closure of social and lifestyle venues (mean preference, 0.05; 95% CI, -0.08 to 0.17). There were weak preferences to keep outdoor venues (mean preference, 0.50; 95% CI, 0.39 to 0.61) and schools (mean preference, 0.18; 95% CI, 0.05 to 0.30) open. Latent class analysis revealed 4 distinct preference phenotypes in the population: risk averse (48.9%), conflicted (22.5%), prosocial (14.9%), and back to normal (13.7%), with men twice as likely as women to belong to the back to normal group than the risk averse group (relative risk ratio, 2.19; 95% CI, 1.54 to 3.12). In this survey study using a discrete choice experiment, public health policies that prohibited large gatherings, as well as those that closed social and lifestyle venues, appeared to be acceptable to the public. During policy implementation, these activities should be prioritized for first-phase closures. These findings suggest that policy messages that address preference heterogeneity (eg, focusing on specific preference subgroups or targeting men) could improve adherence to social distancing measures for COVID-19 and future pandemics.


Histopathological Pattern Of Soft Tissues Tumors And Tumour Like Lesions In The Pathology Department Of Lady Reading Hospital Peshawar, Pakistan.
Soft tissues tumours are tumours of mesenchymal origin excluding epithelial, skeletal tissue, reticuloendothelial system, brain coverings and solid viscera of the body. The objective of this study was to know the histopathological pattern of soft tissues tumours in the Pathology Department of Lady Reading Hospital Peshawar Khyber Pakhtunkhwa Pakistan. This descriptive study was conducted on retrospective data from January 2009 to December 2013. All the soft tissues biopsy specimens were received in 10% formalin, labelled, gross performed, sections processed in alcohol, xylene, wax, block prepared, frozen, microtome sections taken and processed for H&E staining, mounted and reported by a Histopathologist. The inclusion criteria were any sufficient soft tissue tumour biopsy specimen of any age, sex, location in body whereas the exclusion criteria were autolysed biopsy specimen. A minimum of four and maximum of eight sections and 5 micron thick were taken from each specimen. A total of 267 soft tissues tumours biopsy specimens were received in the pathology laboratory with age range of 1-75 years, with mean age of 30.68±17.71 years. Male to female ratio was 1.13:1. Amongst the total, benign tumours were 176 (65.91%). Haemangioma, 73 (27.3%) was the commonest tumours followed by lipomas 41 (15.4%) cases. Amongst the total malignant tumours, i.e., 91 (34.08%), rhabdomyosarcoma, 35 (13.1%) was the commonest tumour followed by angiosarcoma 14 (5.2%) cases. Haemangioma is the commonest benign tumour and rhabdomyosarcoma is the commonest malignant tumour in this study.


Frequency of Intake and Type of Away-from- Home Foods Consumed Are Associated with Diet Quality in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL).
Away-from-home foods (AFHFs) influence diet quality, a modifiable obesity risk factor, with limited generalizable evidence in Hispanic/Latino adults. We investigated associations between AFHF intake with diet quality and overweight or obesity among US Hispanic/Latino adults. Cross-sectional baseline (2008-2011) analyses included adults (n = 16,045) aged 18-74 y in the national Hispanic Community Health Study/Study of Latinos. Participants self-reported AFHF consumption frequency from 10 different settings and dietary intake (2-d 24-h recall). The Alternate Healthy Eating Index-2010 (AHEI-2010) was used to measure diet quality; higher scores indicated a healthier diet and scores were categorized into tertiles. WHO classifications categorized overweight [body mass index (BMI; kg/m2): 25.0-29.9] and obesity (BMI ≥30). Multivariate-adjusted associations of AFHF frequency or type with AHEI-2010, overweight, or obesity were assessed by using complex survey logistic regression (ORs and 95% CIs). Almost half of participants (47.1%) reported eating AFHFs ≥5 times/wk. The mean ± SE AHEI-2010 score was 47.5 ± 0.2. More than one-third (37.2%) were classified as overweight and 39.6% classified as obese. Compared with consuming AFHFs ≥5 times/wk, consuming AFHFs <1 time/wk or 1-2 times/wk was associated with greater odds of being in higher AHEI-2010 tertiles, indicating a healthier diet [<1 time/wk-tertile 2: OR (95% CI): 1.6 (1.4, 1.9); tertile 3: 2.5 (2.1, 3.1); 1-2 times/wk-tertile 2: OR (95% CI): 1.4 (1.2, 1.6); tertile 3: 1.5 (1.2, 1.8)]. Consumption of AFHFs ≥1 time/wk from each AFHF setting, compared with consumption of any AFHFs <1 time/wk was associated with lower odds of being in higher AHEI-2010 tertiles. Increasing AFHF intake frequency was not associated with odds of overweight or obesity. Eating from on-street vendors ≥1 time/wk was associated with obesity (OR: 1.5; 95% CI: 1.1, 2.0). Consumption of AFHFs was prevalent among Hispanic/Latino adults and was associated with poorer diet quality. Findings may help to identify dietary targets to improve diet quality and prevent obesity in US Hispanics/Latinos.


Calcification and proteoglycan accumulation following balloon angioplasty and stenting.
To examine in a porcine model if a correlation exists between calcification and the hyperplastic response of arteries to balloon angioplasty and stenting. Eleven Sinclair miniature swine on an atherogenic diet underwent balloon angioplasty or endovascular stenting in nondiseased external iliac arteries using standard procedures. Ninety days postoperatively, the animals were euthanized, and histological sections of the dilated, stented, and control arteries were examined for evidence of calcification and increased proteoglycan accumulation. An increase in proteoglycan accumulation and the loss of integrity of the internal elastic lamina were observed in both the dilated and stented arteries. Diffuse calcification was seen in the media/neomedia of both groups, and large calcium salt deposits were observed in the dilated arteries at the site of the internal elastic lamina and near the stent struts in stented arteries. Internal elastic lamina loss of integrity appears to be related to an increase in proteoglycans through the formation of a neointima, and the arterial hyperplastic response to balloon angioplasty and stenting seems to lead to calcification.


Elevated cytokine levels in synovial fluid of rheumatoid arthritis correlates with the presence of cytomegalovirus genome.
Synovial fluid aspirated from 34 patients with symptomatic rheumatoid arthritis (RA) was evaluated for the presence of human cytomegalovirus (CMV) genomic material using polymerase chain reaction (PCR), and for levels of interleukin 8 (IL-8) and IL-6 using enzyme-linked immunoadsorbence assay. IL-8 and IL-6 levels were significantly higher in CMV DNA-positive RA patients than CMV DNA-negative RA patients and at least 10-fold higher than in both corresponding control groups of patients with osteoarthritis (OA). These findings suggest an association between elevated IL-8 and IL-6 levels and the presence of the CMV genome in RA patients.


Enhanced photoelectrochemical performance of internally porous Au-embedded α-Fe2O3 photoanodes for water oxidation.
We report internally porous Au-embedded hematite on FTO using CTAB. Incorporation of Au and CTAB synergistically improved the photocurrent of hematite by 63% at 1.23 VRHE in 1 M NaOH under standard illumination conditions. The performance enhancement is due to the increased donor density and optical properties of internally porous networks and plasmonic absorption of hematite.


Pacifiers in the NICU: a lactation consultant's view.
Many infants, especially premature infants, may benefit from the regular use of pacifiers in the NICU. The NICU nurse who has a variety of pacifiers to choose from can select the one that best meets the infant's needs. But although mother's milk at the breast may not be the choice of all mothers, or may not be an option, it ought to be viewed as the norm. Full-term infants at the breast generally do better with no pacifiers at all. For the NICU patient, smooth transition to successful oral feedings at the breast or bottle is an important step in the direction of home.


Initialization method for speech separation algorithms that work in the time-frequency domain.
This article addresses the problem of the unsupervised separation of speech signals in realistic scenarios. An initialization procedure is proposed for independent component analysis (ICA) algorithms that work in the time-frequency domain and require the prewhitening of the observations. It is shown that the proposed method drastically reduces the permuted solutions in that domain and helps to reduce the execution time of the algorithms. Simulations confirm these advantages for several ICA instantaneous algorithms and the effectiveness of the proposed technique in emulated reverberant environments.


Relationship between Amphipathic β Structures in the β1 Domain of Apolipoprotein B and the Properties of the Secreted Lipoprotein Particles in McA-RH7777 Cells.
Our previous studies demonstrated that the first 1000 amino acid residues (the βα1 domain) of human apolipoprotein (apo) B-100, termed apoB:1000, are required for the initiation of lipoprotein assembly and the formation of a monodisperse stable phospholipid (PL)-rich particle. The objectives of this study were (a) to assess the effects on the properties of apoB truncates undergoing sequential inclusion of the amphipathic β strands in the 700 N-terminal residues of the β1 domain of apoB-100 and (b) to identify the subdomain in the β1 domain that is required for the formation of a microsomal triglyceride transfer protein (MTP)-dependent triacylglycerol (TAG)-rich apoB-containing particle. Characterization of particles secreted by stable transformants of McA-RH7777 cells demonstrated the following. (1) The presence of amphipathic β strands in the 200 N-terminal residues of the β1 domain resulted in the secretion of apoB truncates (apoB:1050 to apoB:1200) as both lipidated and lipid-poor particles. (2) Inclusion of residues 300-700 of the β1 domain led to the secretion of apoB:1300, apoB:1400, apoB:1500, and apoB:1700 predominantly as lipidated particles. (3) Particles containing residues 1050-1500 were all rich in PL. (4) There was a marked increase in the lipid loading capacity and TAG content of apoB:1700-containing particles. (5) Only the level of secretion of apoB:1700 was markedly diminished by MTP inhibitor BMS-197636. These results suggest that apoB:1700 marks the threshold for the formation of a TAG-rich particle and support the concept that MTP participates in apoB assembly and secretion at the stage where particles undergo a transition from PL-rich to TAG-rich.


Perinatal and social factors predicting caesarean birth in a 2004 Australian birth cohort.
The proportion of babies born by caesarean section in Australia has almost doubled over the last 25 years. Factors known to contribute to caesarean such as higher maternal age, mothers being overweight or obese, or having had a previous caesarean do not completely account for the increased rate and it is clear that other influences exist. To identify previously unsuspected risk factors associated with caesarean using nationally-representative data from the Longitudinal Study of Australian Children. Data were from the birth cohort, a long-term prospective study of approximately 5000 children that includes richly-detailed data regarding maternal health and exposures during pregnancy. Logistic regression was used to examine the contribution of a wide range of pregnancy, birth and social factors to caesarean. 28% of 4862 mothers were delivered by caesarean. The final adjusted analyses revealed that use of diabetes medication (OR=3.1, 95% CI=1.7-5.5, p<0.001) and maternal mental health problems during pregnancy (OR=1.3, CI=1.1-1.6, p=0.003) were associated with increased odds of caesarean. Young maternal age (OR=0.6, CI=0.5-0.7, p<0.001), having two or more children (OR=0.7, CI=0.6-0.9, p<0.001), and fathers having an unskilled occupation (OR=0.7, CI=0.6-1.0, p=0.036) were associated with reduced odds of caesarean. Our findings raise the prospect that the effect of additional screening and support for maternal mental health on caesarean rate should be subject of prospective study.


Environmental Impacts Assessment in Suspension PVC Production Process Using Computer-Aided Process Engineering.
The new demands for sustainable operation in the chemical industry due to increasing environmental regulations and agreements have generated the need to adapt existing processes to more intelligent production. The plastics sector is in a complex position due to its contribution to economic development and the climate crisis. Therefore, environmental assessment has become an important tool due to the benefits it provides by quantifying the environmental performance of processes, allowing it to balance operational and environmental needs. Polyvinyl chloride (PVC) is one of the most globally used polymers thanks to its resistance, flexibility, and cost-effectiveness. The polymer is synthetized by suspension polymerization, which is characterized by high productivity and controllability. However, it presents problems associated with intensive energy consumption and the emission of toxic substances and greenhouse gases. Therefore, an environmental assessment of the suspension PVC production process was performed using the waste reduction algorithm (WAR). The potential environmental impact (PEI) was quantified using the generation rate and the output velocity for four cases and three different fuels. It was found that the process transforms raw materials with high impacts, such as VCM, into substances with lower PEI, such as PVC. However, the process has a high generation of PEI due to the effects of energy consumption (-2860, -2410, 3020, and 3410 for cases 1-4, respectively). The evaluation of the toxicological impacts shows that the ATP category is the only one that presents a positive generation value (75 PEI/day); the product contributes to the formation and emission of impacts. The atmospheric categories showed that the energy consumption of the process is the most critical aspect with a contribution of 91% of the total impacts emitted. The AP and GWP categories presented the highest values. It was determined that the most suitable fuel is natural gas; it has lower impacts than liquid and solid fuels (coal). Additionally, it can be concluded that the PVC production process by suspension is environmentally acceptable compared to the polyethylene or polypropylene processes, with output impacts 228 and 2561 times lower, respectively.


Renal oncocytoma of the native kidney after renal transplantation.
Patients with acquired cystic kidney disease (ACKD) are at an increased risk of renal neoplasms. Frequent tumors are adenomas and renal cell carcinomas. However, renal oncocytomas may occur in patients with ACKD. Little is known about oncocytomas of the native kidney following renal transplantation. By means of B scan ultrasonography, a solid and echo-inhomogeneous renal mass was incidentically observed in the right native kidney of a 28-year-old female patient with ACKD 4 years following renal transplantation. A nephrectomy was performed. The histological examination revealed a renal oncocytoma. The increased prevalence of neoplasms in the case of ACKD and following renal transplantation requires careful monitoring of the patients concerned. In very rare cases a renal oncocytoma may develop in the native kidney after renal transplantation.


Bending affects entropy of semiflexible polymers: Application to protein-DNA complexes.
We discuss a class of generalized wormlike chain models of polymers with spontaneous curvature and show that the density of states and consequently the entropy of such natively bent polymers are higher than that of straight ones. This effect changes the classical Langmuir binding isotherm by giving rise to enhanced binding of DNA-bending proteins.


[Experience with pyoktanin lavage for mediastinitis and prosthetic graft infection following thoracic aortic surgery].
Pyoktanin, a triphenylmethane dye, is known to have a potent bactericidal activity against Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA). We used pyoktanin for irrigating wounds in 2 cases of mediastinitis and prosthetic graft infection following thoracic aortic surgery. Case 1 is mediastinitis and prosthetic graft infection due to Staphylococcus epidermidis following Cabrol procedure. After irrigating the anterior mediastinum with 0.1% pyoktanin solution twice a day for 8 days, omental transposition was performed, which let to cure of the infection. Case 2 is mediastinitis due to methicillin-resistant Staphylococcus epidermidis following ascending aortic and aortic arch replacement for acute type A aortic dissection. After irrigating the wound with 0.1% pyoktanin solution twice a day for 14 days, the wound was closed primarily, which resulted in cure of the infection of the wound. Using pyoktanin at low concentrations for irrigating wound for a short period of time is considered permissible and effective for mediastinitis and prosthetic graft infection due to Gram-positive bacteria including MRSA.


Energetic and dynamic: how mitochondria meet neuronal energy demands.
Mitochondria are the power houses of the cell, but unlike the static structures portrayed in textbooks, they are dynamic organelles that move about the cell to deliver energy to locations in need. These organelles fuse with each other then split apart; some appear anchored and others more free to move around, and when damaged they are engulfed by autophagosomes. Together, these processes-mitochondrial trafficking, fusion and fission, and mitophagy-are best described by the term "mitochondrial dynamics". The molecular machineries behind these events are relatively well known yet the precise dynamics in neurons remains under debate. Neurons pose a peculiar logistical challenge to mitochondria; how do these energy suppliers manage to traffic down long axons to deliver the requisite energy supply to distant parts of the cell? To date, the majority of neuronal mitochondrial dynamics studies have used cultured neurons, Drosophila larvae, zebrafish embryos, with occasional experiments in resting mouse nerves. However, a new study in this issue of PLOS Biology from Marija Sajic and colleagues provides an in vivo look at mitochondrial dynamics along resting and electrically active neurons of live anaesthetized mice.


Evidence from single nucleotide polymorphism analyses of ADVANCE study demonstrates EFNB3 as a hypertension risk gene.
EPH kinases and their ligands, ephrins (EFNs), have vital and diverse biological functions. We recently reported that Efnb3 gene deletion results in hypertension in female but not male mice. These data suggest that EFNB3 regulates blood pressure in a sex- and sex hormone-dependent way. In the present study, we conducted a human genetic study to assess the association of EFNB3 single nucleotide polymorphisms with human hypertension risks, using 3,448 patients with type 2 diabetes from the ADVANCE study (Action in Diabetes and Vascular Disease: Peterax and Diamicron MR Controlled Evaluation). We have observed significant association between 2 SNPs in the 3' untranslated region or within the adjacent region just 3' of the EFNB3 gene with hypertension, corroborating our findings from the mouse model. Thus, our investigation has shown that EFNB3 is a hypertension risk gene in certain individuals.


Implications of Pharmacokinetic Potentials of Pioglitazone Enantiomers in Rat Plasma Mediated through Glucose Uptake Assay.
Pioglitazone, a PPAR-gamma activator used to diagnose hyperglycemia, was studied for its stereoselective deposition and active enantiomers in female albino Wistar rats. In accordance with USFDA recommendations, a bioanalytical technique was employed to assess the segregation of pioglitazone enantiomers in rat plasma with glimepiride as an internal standard. A Phenomenox i-Amylose-3 column (150 mm × 4.6 mm) of 5 µm was used for high-performance liquid chromatography (HPLC) with a mobile phase of 10 mM ammonium acetate buffer in Millipore water and acetonitrile in 60:40 (v/v) admixture with column temperature 35 °C, wavelength 265 nm, and flow rate 0.6 mL/min, respectively. Pioglitazone-S, Pioglitazone-R, and the internal standard had retention times of 3.1, 7.4, and 1.7 min, respectively. The study found that within-run and between-run precision ranged from 0.1606-0.9889% for Pioglitazone-R and from 0.2080-0.7919% for Pioglitazone-S, while the accuracy ranged from 99.86 to 100.36% for Pioglitazone-R and 99.84 to 99.94% for Pioglitazone-S. In addition, a non-radioactive glucose uptake assay was employed to examine the enantiomers in 3T3-L1 cell lines by flow cytometry. Significant differences were demonstrated in Cmax, AUClast (h*μg/mL), AUCINF obs (h*μg/mL), and AUC%Extrap obs (%) of Pioglitazone-R and S in female albino Wistar rats, suggesting enantioselectivity of pioglitazone.


Aldose Reductase from Porcine Liver Metabolizing 3-Deoxyglucosone, a Maillard Reaction Intermediate.
An enzyme which catalyzes the NADPH-dependent reduction of 3-deoxyglucosone (3DG) was isolated and purified from porcine liver by ammonium sulfate fractionation, and DEAE-cellulose, hydroxyapatite, Sephadex G-100, Blue Sepharose CL-6B, and Sephadex G-100 column chromatographies. The pH for optimum enzyme activity was 6.5. 3DG was a good substrate, and glucose and fructose could also be reduced at a significant rate. The Km values for 3DG, methylglyoxal and glyceraldehyde were 2.5, 1.9, and 4.9 mM, respectively. The molecular mass of the enzyme was estimated to be 67, 000, and the enzyme is proposed to be a dimer composed of identical subunits. The activity of the enzyme was completely inhibited by p-chloromercuribenzoate, and the enzyme is estimated to be an aldose reductase.


Intramural Teflon injection of the ureter for treatment of vesicoureteral reflux: sonographic appearance.
Endoscopic injection of Teflon paste under the submucosal portion of the ureter in the bladder is a new treatment for vesicoureteral reflux. Twenty-one children at The Montreal Children's Hospital and at St. Justine Hospital were treated with this technique over a 2-year period. In 15 children, abdominal sonography was performed 1-5 days after Teflon paste injections. Follow-up sonograms performed 5 weeks to 1 year after the procedure are available in nine children. Sonographically, the Teflon paste at the injection site appears as a hyperechoic focus within the bladder wall with distal shadowing seen postoperatively and on follow-up examinations. This finding occurred in 22 (88%) of 25 treated ureters. The location of Teflon paste after injection as viewed via cystoscopy is correlated with the sonographic appearance. This preliminary report suggests that sonography is useful in determining the location and size of the Teflon mass, in evaluating surrounding soft tissues at various time intervals after injection, and in assessing possible complications such as obstruction.


[Compliance with diagnostic MRI in the workup of sudden sensorineural hearing loss].
Sudden sensorineural hearing loss (SSNHL] can be the presenting symptom of an acoustic neurinoma. High sensitivity and specificity rates define magnetic resonance imaging (MRI) of the brain and internal acoustic canal as the gold standard for the diagnosis of retro-cochlear pathologies. A previous study revealed low compliance rates (49%] for performing an MRI after an episode of SSNHL; 15% of patients who had an MRI were diagnosed with a retro-cochlear pathology. To evaluate current compliance rates for performing an MRI of the brain and internal acoustic canal after an episode of SSNHL. The study cohort included 41 patients, 24 females and 17 male, with an average age of 49.8 +/- 16.8 years (range, 16-78 years), who were diagnosed with SSNHL and admitted for treatment between December 2009 and June 2010. Two months after discharge from hospitalization, only 29 patients (70.7%) returned for the scheduled followup. Only 21 patients (51.2% of those admitted) had an MRI of the brain and internal acoustic canal, as was recommended upon their discharge. Three of those who had an MRI were diagnosed with a retro-cochlear pathology. In 20 patients [48.8%) who did not perform an MRI, a retro-cochlear pathology could not be ruled out. Compliance rates for performing an MRI after an episode of SSNHL haven't changed in recent years. The main reason seems to be poor patients' compliance, as well as their general practitioners and health insurance companies. Ruling out retro-cochlear pathologies by means of MRI is highly important and considered common medical practice. Guidelines regarding the importance of MRI after an episode of SSNHL should be updated and reinforced.


Difficult Family Relationships, Residential Greenspace, and Childhood Asthma.
Both the social environment and the physical environment are increasingly recognized as important to childhood diseases such as asthma. This study tested a novel hypothesis: that living in areas high in greenspace may help buffer the effects of difficult family relationships for children with asthma. A total of 150 children (ages 9-17), physician-diagnosed with asthma, participated in this study. To assess difficulties in parent-child relationships, parents and children completed measures of harsh/inconsistent parenting and parental hostility. Residential greenspace was calculated by using satellite-derived Normalized Difference Vegetation Index with a buffer of 250 m around the residential address. Outcomes included both clinical and biological measures: asthma control and functional limitations, as well as airway inflammation (fractional concentration of exhaled nitric oxide) and glucocorticoid receptor expression in T-helper cells. After controlling for potential confounding variables, including family income, child demographics, and child medical variables, few main effects were found. However, interactions between residential greenspace and difficult family relationships were found for asthma control (P = .02), asthma functional limitations (P = .04), airway inflammation (P = .007), and the abundance of glucocorticoid receptor in T-helper cells (P = .05). These interactions were all in a direction such that as the quality of parent-child relationships improved, greenspace became more strongly associated with better asthma outcomes. These findings suggest synergistic effects of positive environments across the physical and social domains. Children with asthma appear to benefit the most when they both live in high greenspace areas and have positive family relationships.


Lipidomics of facial sebum in the comparison between acne and non-acne adolescents with dark skin.
Lipidomics is advantageous in the study of sebum perturbations occurring in acne. An extended evaluation of the sebum lipid profiles in acne-prone sebaceous areas is lacking in dark skin. Yet, there is a void space in understanding how the building blocks of sebum lipids, i.e. individual fatty acids (FAs), are intertwined with acne-prone skin. We aimed to determine the sebum lipidome in facial areas of adolescents with and without acne in Nigeria. A cross-sectional analytical study was conducted in 60 adolescents/young adults divided in 30 acne patients (15F, 15M) and 30 age and sex-matched controls. Sebum samples obtained from foreheads and cheeks were analysed separately by gas chromatography-mass spectrometry (GCMS) and thin layer chromatography (HPTLC). Distributions of sebum components were investigated with multivariate ANOVA-simultaneous component analysis (ASCA). Sebum incretion in acne was paralleled by significantly higher abundance of triglycerides, wax esters, and squalene together with monounsaturated FAs (MUFAs), and straight chain saturated FAs (SFAs), especially those with odd-carbon chain, i.e. C13:0, C15:0, and C17:0. Profiling weight/weight percentage of individual components revealed that, in acne, the free FAs (FFAs) array was shifted towards higher relative abundance of the SFAs C15:0, C16:0, and C17:0 and lower percentage of the anteiso-branched FFAs with 12, 14, 16, and 18 carbons. In acne patients, MUFAs and PUFAs were quantitatively increased and decreased on foreheads and cheeks, respectively. Relative abundance of fatty alcohols was decreased in acne independent on the site. The results indicated that acne associates with site-specific derangement of the pathways regulating the balance among odd straight-chain and branched-chain SFAs, MUFAs, which included sapienate (C16:1n-10), PUFAs, and squalene.


Organization of the fimbrial gene region of Bacteroides nodosus: class I and class II strains.
The fimbrial subunit genes of Bacteroides nodosus may be divided into two distinct classes, based on the sequence of the major subunit gene fimA (accompanying paper--Mattick et al., 1991). The genetic organization of the fibrial gene region in these two classes is also distinct. Upstream of fimA in both classes in opposite transcriptional orientation is the gene aroA which encodes amino acid biosynthetic enzyme 5-enolpyruvylshikimate-3-phosphate synthase. However, downstream of fimA the two classes are quite different until homology is restored at a bidirectional transcription termination signal separating the fimbrial operon from a gene clpB, which appears to encode the regulatory subunit of an ATP-dependent protease. Between aroA and clpB class I strains contain, apart from fimA, only one other gene (fimB). Sequence and polymerase chain reaction analyses indicate that fimB does not have a separate promoter but rather is co-transcribed with fimA at a level attenuated by the strength of the transcription termination signal in the intergenic region. In class II strains fimA is followed by a more extended region containing three genes, which appear to have the same transcriptional arrangement as fimB. The second of these genes (fimD) may represent a functional analogue of fimB although there is no close sequence homology. The first gene (fimC) has no obvious similarity to either fimB or fimD. Beyond fimD, at the 3' end of the class II-specific region, is a variant fimbrial subunit gene (fimZ) which is virtually identical in serogroups D and H and which appears to represent a duplicate, possibly redundant, gene closely related to the progenitor of the more divergent structural subunit fimA gene found in these strains. Comparisons of the predicted fimZ product with those of fimA in class I and class II strains, as well as of the boundaries of the class-specific regions, suggest that the class II sequences evolved in another type 4 fimbriate species and were subsequently substituted in the B. nodosus genome by lateral transfer. Analysis of the sequences flanking fimA in different strains indicates that recombinational exchange of both fimA and the entire operon has also occurred between strains, and is possibly a mechanism for disseminating structural diversity in the population.


Plastic materials currently used in Mongolia.
The first skin-flap procedures were performed in Mongolia by a team of Chinese doctors (Chenod, Chen) who treated children with burn injuries in the 1950s. The field of plastic surgery was further developed through assistance from the former Soviet Union and is now widely practiced by a number of surgeons around the country. In recent years, the fast evolving field of plastic surgery in Mongolia has created a need for clear and consistent system for the classification of various plastic materials. A team of Mongolian surgeons at the National Hospital for Traumatology, Orthopedics, Rehabilitation and Teaching Research have completed a research programme aimed at adopting a leading classification system that can facilitate effective communication between plastic surgeons. This requires the chosen system to be in line with modern trends in plastic surgery and the established international norms. As a result of extensive research and analysis, they have developed a customized version of Vasiliev's classification that focuses on formulating general principles of the description of plastic materials based on their functional characteristics. The main reason for this selection is its similarity with existing Mongolian standards as well as its principles that contain important implications for surgery.


Interpretative variability and its impact on the prognostic value of myocardial fatty acid imaging in asymptomatic hemodialysis patients in a multicenter trial in Japan.
The severity of impaired fatty acid utilization in the myocardium can predict cardiac death in asymptomatic patients on hemodialysis. However, interpretive variability and its impact on the prognostic value of myocardial fatty acid imaging are unknown. A total of 677 patients who received hemodialysis for ≥ 20 years and had one or more cardiovascular risk factors underwent (123)I-labeled β-methyl iodophenyl-pentadecanoic acid (BMIPP) single-photon emission computed tomography (SPECT) at 48 hospitals across Japan. SPECT images were interpreted by experts at the nuclear core laboratory and by readers with varying skill levels at clinical centers, based on the standard 17-segment model and 5-point scoring systems, independently. The κ values only reached fair agreement both for overall impression (κ=0.298, normal vs. abnormal) and for categorical impression (κ=0.244, normal vs. mildly abnormal vs. severely abnormal). The normalcy rate was lower in readers at the clinical centers (60.9%) than in experts (69.9%). In contrast to the results assessed by experts, a Kaplan-Meier analysis based on the interpretation by readers at the clinical centers failed to distinguish the risk of events in patients with normal scans from that of patients with mildly abnormal scans. Considerable variability and its impact on prognostic value were observed in the visual interpretation of BMIPP SPECT images between experts and readers at the clinical centers.


Renewable urea sensor based on a self-assembled polyelectrolyte layer.
A renewable urea sensor based on a carboxylic poly(vinyl chloride) (PVC-COOH) matrix pH-sensitive membrane has been proposed, in which a positively charged polyelectrolyte layer is first constructed by using a self-assembly technique on the surface of a PVC-COOH membrane, and urease, with negative charges, is then immobilized through electrostatic adsorption onto the PVC-COOH membrane, by controlling the pH of the urease solution below its isoelectric point. The response characteristics of the PVC-COOH pH-sensitive membrane and the effects of experimental conditions have been investigated in detail. Compared with conventional covalent immobilization, the urea sensor made with this self-assembly immobilization shows significant advantage in terms of sensitivity and ease of regeneration. The potential responses of the urea sensor with self-assembly immobilization increase with the urea concentration over the concentration range 10(-5) - 10(-1) mol l(-1), and the detection limit is 0.028 mmol(-1). Moreover, this type of urea sensor can be repeatedly regenerated by using a simple washing treatment with 0.01 mol l(-1) NaOH (containing 0.5 mol l(-1) NaCl) and 0.01 mol l(-1) HCl. The urease layers and the polyelectrolyte layers on the PVC-COOH membrane are removed, the potential response of the sensor to urea solutions of different concentrations returns nearly to zero, and another assembly cycle of urease and polyelectrolyte can then be carried out.


Acute Bilateral Cataract in Type 1 Diabetes Mellitus.
We report a case of a 17-year old boy, who presented acute bilateral cataract and complete vision loss within six days, three months after the diagnosis of Type 1 Diabetes Mellitus (T1DM) under optimal metabolic control (HbA1c 6%). At presentation (HbA1c 10.4%) and after correction of diabetic ketoacidosis (pH 6.917) and the beginning of intensified insulin treatment with insulin glargine once daily and insulin aspart before meals,the patient underwent full ophthalmologic examination,which was completely normal. Only few cases with acute bilateral cataract - all relatively shortly after the diagnosis of T1DM - have been reported. Several hypotheses have been drawn but the exact mechanism of this phenomenon remains unclear. The interesting finding in our case was the clearly elevated insulin autoantibodies (IAA) at the time of cataract formation, negative however at presentation. The relation between the elevation of IAA and cataract formation should be further investigated in diabetic patients.


Validation of cardiac output studies from the Mostcare compared to a pulmonary artery catheter in septic patients.
The Mostcare monitor is a non-invasive cardiac output monitor. It has been well validated in cardiac surgical patients but there is limited evidence on its use in patients with severe sepsis and septic shock. The study included the first 22 consecutive patients with severe sepsis and septic shock in whom the floatation of a pulmonary artery catheter was deemed necessary to guide clinical management. Cardiac output measurements including cardiac output, cardiac index and stroke volume were simultaneously calculated and recorded from a thermodilution pulmonary artery catheter and from the Mostcare monitor respectively. The two methods of measuring cardiac output were compared by Bland-Altman statistics and linear regression analysis. A percentage error of less than 30% was defined as acceptable for this study. Bland-Altman analysis for cardiac output showed a Bias of 0.31 L.min-1, precision (=SD) of 1.97 L.min-1 and a percentage error of 62.54%. For Cardiac Index the bias was 0.21 L.min-1.m-2, precision of 1.10 L.min-1.m-2 and a percentage error of 64%. For stroke volume the bias was 5 mL, precision of 24.46 mL and percentage error of 70.21%. Linear regression produced a correlation coefficient r2 for cardiac output, cardiac index, and stroke volume, of 0.403, 0.306, and 0.3 respectively. Compared to thermodilution cardiac output, cardiac output studies obtained from the Mostcare monitor have an unacceptably high error rate. The Mostcare monitor demonstrated to be an unreliable monitoring device to measure cardiac output in patients with severe sepsis and septic shock on an intensive care unit.


No hospital left behind? Education policy lessons for value-based payment in healthcare.
Value-based payment systems have been widely implemented in healthcare in an effort to improve the quality of care. However, these programs have not broadly improved quality, and some evidence suggests that they may increase inequities in care. No Child Left Behind is a parallel effort in education to address uneven achievement and inequalities. Yet, by penalizing the lowest performers, No Child Left Behind's approach to accountability has led to a number of unintended consequences. This article draws lessons from education policy, arguing that financial incentives should be designed to support the lowest performers to improve quality.


[Exocrine pancreas insufficiency: clinical significance and approaches to correction from evidence medicine].
Exocrine pancreatic insufficiency (EPI) is a common complication of both benign and malignant diseases of the pancreas, as well as a consequence of radical surgical operations on the pancreas and a whole range of other variable extra-pancreatic causes. In clinical practice in the adult population, most cases of EPI are associated with chronic pancreatitis, while in the pediatric population with cystic fibrosis. The regression of the production of digestive enzymes in EPI mediates the development of the syndrome of maldigestion and malabsorption, leading to the progressive development of malnutrition, the importance of which is often underestimated by practitioners. At the same time, the development of nutritional deficiency is not just a complication of EPI, but also has an important effect on the course of the underlying causative disease, worsening the prognosis and quality of life of the patient, and is also a proven risk factor for osteoporosis and sarcopenia. To date, compensation for the absolute deficiency of pancreatic enzymes using enzyme replacement therapy is the only possible way to correct the EPI and prevent nutritional deficiency.


Mathematical model for preoperative identification of obstructed nasal subsites.
The planning of experimental studies for evaluation of nasal airflow is particularly challenging given the difficulty in obtaining objective measurements in vivo. Although standard rhinomanometry and acoustic rhinometry are the most widely used diagnostic tools for evaluation of nasal airflow, they provide only a global measurement of nasal dynamics, without temporal or spatial details. Furthermore, the numerical simulation of nasal airflow as computational fluid dynamics technology is not validated. Unfortunately, to date, there are no available diagnostic tools to objectively evaluate the geometry of the nasal cavities and to measure nasal resistance and the degree of nasal obstruction, which is of utmost importance for surgical planning. To overcame these limitations, we developed a mathematical model based on Bernoulli's equation, which allows clinicians to obtain, with the use of a particular direct digital manometry, pressure measurements over time to identify which nasal subsite is obstructed. To the best of our knowledge, this is the first study to identify two limiting curves, one below and one above an average representative curve, describing the time dependence of the gauge pressure inside a single nostril. These upper and lower curves enclosed an area into which the airflow pattern of healthy individuals falls. In our opinion, this model may be useful to study each nasal subsite and to objectively evaluate the geometry and resistances of the nasal cavities, particularly in preoperative planning and follow-up.


Effect of synthetic and natural secretin on the function of the exocrine pancreas in man.
The action of synthetic and natural secretin on the human exocrine pancreas was compared. The trial was an intrasubject crossover comparison with randomized allocation of compounds in 12 healthy male subjects. No significant difference between compounds was found in bicarbonate, amylase and trypsin secretion after bolus injection. However, synthetic secretin evoked a significantly greater volume and amount of bicarbonate after infusion than the natural compound whilst no difference resulted in the other variables. It is concluded that synthetic secretin is suitable for testing the function of the exocrine pancreas.


Bone quantity and quality of youths working on a farm-a pilot study.
This study investigated the effect of farm-related activities on the bone health of youths. Bone quantity and bone quality were quantitated in 36 adolescents-18 youth with a history of working on farms and 18 youth not involved in farm-related activities. Bone quantity as depicted by bone mineral density (BMD) was measured with dual-energy x-ray absorptiometry. Bone quality was characterized with biomechanical measures based on bone geometry and measures of dynamic bone shock absorption (BSA) properties. Dynamic bone response measures provide preliminary evidence that farm-related physically demanding tasks lead to changes that may predispose the teenagers to degenerative skeletal disorders later in life. Future studies with larger samples need to be carried out to further support the findings.


[Assessment of nasal obstruction treatment with the rhinomanometric examination].
The aim of the present study was to assess of nasal obstruction treatment by means of rhinomanometry at patients with deviation of the nasal septum and with rhinitis allergic or vasomotor. The research encompassed 171 patients with nasal obstruction, medicated in Department ENT, who were assigned to 6 different groups according to nasal obstruction reason: group I--42 patients with deviation of the nasal septum, group II--32 patients and group III--34 patients deviation of the nasal septum and with allergic rhinitis, group IV--33 patients and group V--30 patients with deviation of the nasal septum and vasomotor rhinitis and 30 healthy subject forming control group. In groups I, II and IV patients performed plastic surgery of nasal septum and group II and IV performed inferior nasal concha surgery. Laboratory norms for rhinomanometry were fixed on the basis of healthy control group results analysis. After the surgical treatment normal results in rhinomanometry were found: in group I 81%, in group II 53%, in group III 62%, in group IV 51% and in group V 63% patients.