Antibiotic binding to monozinc CphA beta-lactamase from Aeromonas hydropila: quantum mechanical/molecular mechanical and density functional theory studies.
The active-site dynamics of apo CphA beta-lactamase from Aeromonas hydropila and its complex with a beta-lactam antibiotic molecule (biapenem) are simulated using a quantum mechanical/molecular mechanical (QM/MM) method and density functional theory (DFT). The quantum region in the QM/MM simulations, which includes the Zn(II) ion and its ligands, the antibiotic molecule, the catalytic water, and an active-site histidine residue, was treated using the self-consistent charge density functional tight binding (SCC-DFTB) model. Biapenem is docked at the active site unambiguously, based on a recent X-ray structure of an enzyme-intermediate complex. The substrate is found to form the fourth ligand of the zinc ion with its 3-carboxylate oxygen and to hydrogen bond with several active-site residues. The stability of the metal-ligand bonds and the hydrogen-bond network is confirmed by 500 ps molecular dynamics simulations of both the apo enzyme and the substrate-enzyme complex. The structure and dynamics of the substrate-enzyme complex provide valuable insights into the mode of catalysis in such enzymes that is central to the bacterial resistance to beta-lactam antibiotics.


Effects of different heel-raise-lower exercise interventions on the strength of plantarflexion, balance, and gait parameters in stroke survivors.
The objective of this study was to investigate the effects of Heel-Raise-Lower Exercise (HRLE) interventions on the strength of plantarflexion, balance, and gait parameters in people with stroke. Specifically, this study compared the two different HRLEs to identify whether heels raise-lower with forefoot on a block (HRB) is more effective or ineffective to enhance strength and functional capacities than heels raise-lower on a level floor (HRL) exercise in people with stroke. Repetitive heel raise-lower is a common exercise for improving the strength and power of ankle plantarflexors. It is a simple movement, requires no equipment, and can be performed at home. Each group of 10 people with stroke was given either HRB training or HRL training. The subjects performed the exercise 100 times per day, 5 days per week for 6 weeks. The strength of plantarflexors, static/dynamic balance, and gait parameters were measured using the manual muscle test (MMT), a Biodex Balance System (BBS) SD, and the GAITRite system. After 6 weeks of treatment, there were significant increases in the plantarflexors strength in both groups: by 34% in the HRB group and by 21% in the HRL group. Static and dynamic balance and gait speed also increased significantly in both groups. However, cadence, the paretic side single limb support period (SLSP), paretic side step length, and paretic side stride length significantly increased only in the HRB group. The HRB improved significantly the plantar flexor strength of the paretic side, gait speed, and cadence compared to the HRL.


Diterpenoids of terrestrial origin.
This review covers the isolation and chemistry of the diterpenoids from terrestrial as opposed to marine sources and includes labdanes, clerodanes, abietanes, pimaranes, kauranes, gibberellins, cembranes and their cyclization products and taxanes. There are 161 references.


Higher habitual dietary flavonoid intake associates with lower central blood pressure and arterial stiffness in healthy older adults.
Flavonoids have shown anti-hypertensive and anti-atherosclerotic properties: the impact of habitual flavonoid intake on vascular function, central haemodynamics and arterial stiffness may be important. We investigated the relationship between habitual flavonoid consumption and measures of central blood pressure and arterial stiffness. We performed cross-sectional analysis of 381 non-smoking healthy older adults (mean age 66·0 (sd 4·1) years; BMI, 26·4 (sd 4·41) kg/m2; 41 % male) recruited as part of the Australian Research Council Longevity Intervention study. Flavonoid intake (i.e. flavonols, flavones, flavanones, anthocyanins, isoflavones, flavan-3-ol monomers, proanthocyanidins, theaflavins/thearubigins and total consumption) was estimated from FFQ using the US Department of Agriculture food composition databases. Measures of central haemodynamics and arterial stiffness included systolic blood pressure (cSBP), diastolic blood pressure (cDBP), mean arterial pressure (cMAP) and augmentation index (cAIx). After adjusting for demographic and lifestyle confounders, each sd/d higher intake of anthocyanins ((sd 44·3) mg/d) was associated with significantly lower cDBP (-1·56 mmHg, 95 % CI -2·65, -0·48) and cMAP (-1·62 mmHg, 95 % CI -2·82, -0·41). Similarly, each sd/d higher intake of flavanones ((sd 19·5) mg/d) was associated with ~1 % lower cAIx (-0·93 %, 95 % CI -1·77, -0·09). These associations remained significant after additional adjustment for (1) a dietary quality score and (2) other major nutrients that may affect blood pressure or arterial stiffness (i.e. Na, K, Ca, Mg, n-3, total protein and fibre). This study suggests a possible benefit of dietary anthocyanin and flavanone intake on central haemodynamics and arterial stiffness; these findings require corroboration in further research.


Interleukin‑1β attenuates the proliferation and differentiation of oligodendrocyte precursor cells through regulation of the microRNA‑202‑3p/β‑catenin/Gli1 axis.
The inflammatory cytokine interleukin (IL)‑1β has been implicated in demyelinating diseases, such as multiple sclerosis and experimental autoimmune encephalomyelitis, and brain degenerative diseases, such as Alzheimer's disease. However, the cellular and molecular mechanisms underlying the damaging effects of IL‑1β on myelination are poorly understood. Therefore, the present study was designed to investigate whether IL‑1β modifies the proliferation and differentiation of oligodendrocyte precursor cells (OPCs) through regulating the miR‑202‑3p/β‑catenin/glioma‑associated oncogene homolog 1 (Gli1) axis. It was observed that IL‑1β significantly attenuated the proliferation and differentiation of OPCs, as evidenced by a decrease in bromodeoxyuridine incorporation and reduced percentage of myelin basic protein‑positive cells among the total number of oligodendrocyte transcription factor 2‑positive cells. In addition, IL‑1β markedly decreased the expression of miR‑202‑3p and increased the protein expression of β‑catenin and Gli1, all of which were reversed by the IL‑1β inhibitor, IL‑1Ra. Treatment with the β‑catenin inhibitor XAV939, Gli1 siRNA, or miR‑202‑3p mimic transfection, attenuated the IL‑1β‑induced suppression of OPC proliferation and differentiation. Treatment with XAV939 decreased the expression of Gli1. Transfection of miR‑202‑3p mimic attenuated the expression of β‑catenin and Gli1. As demonstrated by the findings of the present study, IL‑1β suppressed the proliferation and differentiation of OPCs through regulation of the miR‑202‑3p/β‑catenin/Gli1 axis. Therefore, the miR‑202‑3p/β‑catenin/Gli1 axis may be of value as a therapeutic target in multiple sclerosis.


Reported Dietary Intake and Food Sources of Zinc, Selenium, and Vitamins A, E and C in the Spanish Population: Findings from the ANIBES Study.
Zinc, selenium, and the vitamins A, E and C, all have specific biological functions that are involved mainly in the antioxidant defence system, which has important implications for the development of chronic diseases. We aimed to assess the reported intake of those six nutrients, as well as the food that contributes to their sources of intakes. Data were obtained from the Spanish ANIBES ("Anthropometry, Intake and Energy Balance in Spain") study, n = 2009 (9-75 years old). The analyses were performed in the whole population and in the plausible energy reporters after a misreporting analysis according to the European Food and Safety Authority (EFSA) protocol. A validated, photo-based three-day food record was used to collect the data. Mean (max-min) reported intake for the whole population of zinc was 8.1 ± 0.1 mg/day, (2.3-27.3 mg/day), selenium 75 ± 1 µg/day, (14-265 µg/day), vitamin A 668 µg RE/day (2-11,017 µg RE/day), retinol 364 ± 18 µg/day (0-10,881 µg/day), carotenes 1735 ± 35 µg/day (13-13,962 µg/day), vitamin E 7.0 ± 0.1 mg α-TE/day (0.7-55.2 mg α-TE/day) and vitamin C 84.4 ± 1.4 mg/day (5.0-802.7 mg/day). The main source intakes for zinc were meat and meat products, for selenium cereals and grains, for vitamin E oils and fat, and for vitamin A and C vegetables. There is an elevated percentage of the Spanish ANIBES population not meeting the EFSA recommended intakes for all analysed micronutrients: zinc (83%), vitamin A (60%), vitamin E (80%), vitamin C (36%) and selenium (25%).


Lipocalins of boar salivary glands binding odours and pheromones.
Large amounts of an odorant-binding protein have been isolated from submaxillary glands of mature male pig. This polypeptide molecule is sex-specific, being absent in females. On electrophoretic gels under denaturing conditions it migrated as a broad band with an apparent molecular mass of around 20 kDa. Electrospray mass spectrometry revealed the presence of three main components, whose mass differences are not interpretable as result of any common post-translational modifications, indicating the presence of distinct polypeptide chains. N-terminal Edman degradation yielded a single sequence of 29 amino acids. It includes the lipocalin signature (-G-X-W-) and shows clear homology with a subclass of odorant-binding proteins present in mouse saliva, nasal mucus and urine. The purified protein still retained small ligands tightly bound; among them 5alpha-androst-16-en-3-one and 5alpha-androst-16-en-3alpha-ol, both known sex pheromones for the pig, were identified. The protein also binds 2-isobutyl-3-methoxypyrazine, a good ligand for most odorant-binding proteins, with a dissociation constant of 5 microM.


Renal cell carcinoma.
Renal cell carcinoma continues to be a difficult malignancy to treat because of its ability to spread asymptomatically and its inherent resistance to conventional chemotherapy. However, molecular genetic studies bring new insights into the pathogenesis of this disorder and may provide new targets against which novel chemotherapeutic agents could be developed. Nephron-sparing surgery is also gaining wider acceptance as favorable long-term, cancer-free survival data emerge from clinical trials. For metastatic disease, cytokine therapy continues to be the mainstay of treatment despite marginal efficacy and a significant side-effect profile.


Ordered mesoporous cobalt oxide as highly efficient oxygen evolution catalyst.
Oxygen evolution from water by use of earth-abundant element-based catalysts is crucial for mass solar fuel production. In this report, a mesoporous cobalt oxide with an ultrahigh surface area (up to 250 m(2)·g(-1)) has been fabricated through Mg substitution in the mesoporous Co3O4 spinel, followed by a Mg-selective leaching process. Approximately a third of Mg cations were removed in the leaching process, resulting in a highly porous cobalt oxide with a significant amount of defects in the spinel structure. The activated mesoporous cobalt oxide exhibited high oxygen evolution activities in both the visible-light-driven [Ru(bpy)3](2+)-persulfate system and the Ce(4+)/Ce(3+) chemical water oxidation system. Under a strong acidic environment, a high turnover frequency (TOF) of ~2.2 × 10(-3) s(-1) per Co atom was achieved, which is more than twice the TOF of traditional hard-templated, mesoporous Co3O4.


Enterobiasis and its relationship with anal itching and enuresis among school-age children in Calabar, Nigeria.
The prevalence of enterobiasis and its relationship with anal itching and enuresis were investigated among 799, randomly selected children aged 5-14 years, who lived, either in an area of high population density or one with a much lower population density, in Calabar, Nigeria. The eggs of Enterobius vermicularis were found in anal swabs (collected with transparent adhesive tape) from 60 (7.5%) of the subjects tested, with the prevalence of infection appearing markedly higher in the 403 children from the area with a high population density than in the 396 from the less densely populated area (11.7% v. 3.3%; P < 0.05). Questionnaire-based interviews were used to determine which of the children suffered from anal itching, enuresis or both. Compared with the egg-negative subjects, the 60 children who were egg-positive for Enterobius were found to be much more likely to be suffering from anal itching (78.3% v. 28.3%; P < 0.05) or enuresis (53.3% v. 36.4%; P < 0.05). Enterobiasis is therefore not a problem that is restricted to the temperate regions of the world, and may be a cause of enuresis or at least a contributory factor in the development of this complaint.


Prognostic significance of p16 & p53 immunohistochemical expression in triple negative breast cancer.
p16 and p53 genes are frequently mutated in triple negative breast cancer & prognostic value of these mutations have been shown; however, their role as immunohistochemical overexpression has not been fully validated. Therefore we aimed to evaluate the association of p16 and p53 overexpression in triple negative breast cancer with various prognostic parameters. Total 150 cases of triple negative breast cancers were selected from records of pathology department archives that underwent surgeries at Liaquat National hospital, Karachi from January 2008 till December 2013. ER, PR and Her2neu immunohistochemistry were re-performed to confirm triple negative status. p16 & p53 immunohistochemistry was performed on all cases and association with various clinicopathologic parameters was determined. Mean age of the patients involved in the study was 48.9 years. Most of the patients presented at stage T2 with a high mean ki67 index i.e. 46.9%. 42.7% of cases had nodal metastasis. Although 84% cases were of invasive ductal carcinoma; however a significant proportion of cases were of metaplastic histology (9.3%). Fifty-one percent (76 cases) of cases showed positive p53 expression while 49% (74 cases) were negative. Higher percentage of p53 expression was found to correlate with higher T stage, high ki67 index and higher nodal stage. On the other hand, strong intensity of p53 expression was positively correlated with higher tumor grade and ki67 index. Seventy-one percent (98 cases) of cases showed positive p16 expression, whereas 24.8% (34 cases) were negative and 3.6% (5 cases) showed focal positive p16 expression. However, no significant association was found between p16 expression and various clinical and pathologic parameters. Similarly, no significant association of either p16 or p53 over-expression was noted with recurrence status of patients. On the basis of significant association of p53 over-expression with worse prognostic factors in triple negative breast cancer, therefore we suggest that more large scale studies are needed to validate this finding in loco-regional population. Moreover, high expression of p16 in triple negative breast cancer suggests a potential role of this biomarker in triple negative breast cancer pathogenesis which should be investigated with molecular based research in our population.


Anesthetic and dental management of a child with IMAGe syndrome.
IMAGe syndrome (OMIM 300290) is a rare multisystem disorder that has a broad phenotypic presentation. Though variable, this disorder mainly consists of Intrauterine growth retardation, Metaphyseal dysplasia, Adrenal hypoplasia congenita, and Genital abnormalities. Patients with IMAGe syndrome present as an uncommon yet important challenge for dentists and anesthesiologists due to their wide range of dysmorphic facial features, adrenal insufficiency, electrolyte imbalances, and need for steroid replacement. The purpose of this case report is to describe the successful anesthetic management of a pediatric patient diagnosed with IMAGe syndrome who presented for full mouth dental rehabilitation.


[Consequences of disturbed sex-hormone action in the central nervous system: behavioral, anatomical and functional changes].
Experimental studies revealed that transient action of sex steroids during perinatal period is crucial for the development of male sexual behavior and sexually dimorphic brain anatomy. Meanwhile, the lack of gonadal steroids in female foetus and estrogen effects at puberty determine female behavior together with female type of anatomical brain structures and of endocrine functions. In men psychic sex consists of gender identity (self-estimation), gender role (objective estimation of sex behavior). In addition, a sexual psycho-orientation (hetero-, bi- or homosexual) has been distinguished. Although it is believed that gender depends on the socio-environmental influences such as rearing, learning and individual choice, the biological factors are considered to be most important. This concept arises from recent study on patients with gender dysphoria syndrome (transsexualism). In intersexualism, in genetic men with disturbances of sexual differentiation of external genitalia because of the lack of testoterone production or action in peripheral tissues (male pseudohermaphroditism) or in genetic women with ambiguous genitalia because of the presence and action of androgens (female pseudohermaphroditism), a discordance between the formal sex (assigned after the birth) and the psychic gender may appear. In these individuals the legal sex established according to somatic and/or genetic sex at birth may be incompatible with their actual gender identity and role. The knowledge about gender identity is necessary at the decision of eventual (!) surgical correction of sex organs in patients with ambiguous genitalia. This decision should depend not on the expected, but on the actual gender identity of the individual patient. Meantime, early bilateral gonadectomy in patients with gonadal dysgenesis and male pseudohermaphroditism is an indication for life because of the highest risk of germ cell carcinoma.


Synchronized spontaneous Ca2+ transients in acute anterior pituitary slices.
We investigated the organization of spontaneous rises in cytosolic free Ca2+ concentration ([Ca2+]i) due to electrical activity in acute pituitary slices. Real time confocal imaging revealed that 73% of the cells generated fast peaking spontaneous [Ca2+]i transients. Strikingly, groups of apposing cells enhanced their [Ca2+]i in synchrony with a speed of coactivation >1,000 microm/s. Single-cell injection of Neurobiotin or Lucifer yellow labeled clusters of cells, which corresponded to coactive cells. Halothane, a gap junction blocker, markedly reduced the spread of tracers. Coupling between excitable cells was mainly homologous in nature, with a prevalence of growth hormone-containing cells. We conclude that spontaneously active endocrine cells are either single units or arranged in synchronized gap junction-coupled assemblies scattered throughout the anterior pituitary gland. Synchrony between spontaneously excitable cells may help shape the patterns of basal secretion.


Microscopic bladder neck involvement by prostate carcinoma in radical prostatectomy specimens is not a significant independent prognostic factor.
The independent prognostic importance of microscopic bladder neck involvement by prostate cancer in radical prostatectomy is questionable. We studied a cohort of 1845 patients to determine the significance of microscopic bladder neck involvement. Bladder neck involvement was defined as prostate cancer present within the coned bladder neck. We further categorized the cases as 'true bladder neck involvement' and 'false bladder neck involvement.' True bladder neck involvement required prostate cancer within thick smooth muscle bundles without intermixed benign prostatic glands. False bladder neck involvement was characterized by prostate cancer intermixed with benign prostatic glands. Bladder neck involvement was analyzed in relation to preoperative serum prostate-specific antigen (PSA) level, extraprostatic extension, seminal vesicle involvement, positive surgical margin, lymph node involvement, radical prostatectomy Gleason score, and tumor volume. Of the 90 patients (4.9%) with microscopic bladder neck involvement, 63 were further classified as true bladder neck involvement and 27 as false bladder neck involvement. In univariate model, both types of bladder neck involvement (P<0.001), true (P<0.001), and false (P=0.040), were significantly associated with increased PSA-recurrence risk compared to bladder neck negative cases. In multivariate model the PSA-recurrence relative risk associated with bladder neck involvement (true or false) was not a significant independent prognostic factor. Extraprostatic extension, seminal vesicle involvement, positive surgical margin, lymph node involvement, PSA, and Gleason score were significant independent predictors of PSA recurrence. The time to biochemical recurrence in patients with bladder neck involvement was similar to that of pT2 with positive surgical margin or pT3a with negative surgical margin patients (Kaplan-Meier curves). Bladder neck involvement was associated with other adverse pathologic features, but was not an independent predictor of PSA recurrence. In view of the previous and current data, the staging system for bladder neck involvement should be revised and patients may be best categorized as having pT3a disease.


Simple Laboratory Test Utilization Interventions to Reduce Inappropriate Specialty Coagulation Testing.
The naming convention in coagulation may cause confusion in electronic ordering systems, leading to inappropriate test orders. We implemented test utilization efforts and studied utilization before and after interventions for two specialty coagulation assays. Two interventions were implemented: test names were changed from factor assay to activity, and residents reviewed all factor V and X requests. A retrospective review of factor V and X activity orders was performed for the period 1 year before and after interventions. After interventions, factor V and X activity orders decreased by approximately 40%. Resulted tests decreased by 53.8% and 47.8%, corresponding to reductions of $2,493.05 and $1,867.80 per year in laboratory charges for factor V and factor X activity, respectively. Abnormal factor V activity results increased from 45% to 59%. Factor V activity orders from outpatient clinics decreased by 21.6%. Simple interventions can reduce inappropriate specialty coagulation test orders and unnecessary costs.


Peanut-specific T cell responses in patients with different clinical reactivity.
Whole extract or allergen-specific IgE testing has become increasingly popular in the diagnosis of peanut allergy. However, much less is known about T cell responses in peanut allergy and how it relates to different clinical phenotypes. CD4+ T cells play a major role in the pathophysiology of peanut allergy as well as tolerance induction during oral desensitization regimens. We set out to characterize and phenotype the T cell responses and their targets in peanut sensitized patients. Using PBMC from peanut-allergic and non-allergic patients, we mapped T cell epitopes for three major peanut allergens, Ara h 1, 2 and 3 (27 from Ara h 1, 4 from Ara h 2 and 43 from Ara h 3) associated with release of IFNγ (representative Th1 cytokine) and IL5 (representative Th2 cytokine). A pool containing 19 immunodominant peptides, selected to account for 60% of the total Ara h 1-3-specific T cell response in allergics, but only 20% in non-allergics, was shown to discriminate T cell responses in peanut-sensitized, symptomatic vs non-symptomatic individuals more effectively than peanut extract. This pool elicited positive T cell responses above a defined threshold in 12/15 sensitized, symptomatic patients, whereas in the sensitized but non-symptomatic cohort only, 4/14 reacted. The reactivity against this peptide pool in symptomatic patients was dominated by IL-10, IL-17 and to a lesser extend IL-5. For four distinct epitopes, HLA class II restrictions were determined, enabling production of tetrameric reagents. Tetramer staining in four donors (2 symptomatic, 2 non-symptomatic) revealed a trend for increased numbers of peanut epitope-specific T cells in symptomatic patients compared to non-symptomatic patients, which was associated with elevated CRTh2 expression whereas cells from non-symptomatic patients exhibited higher levels of Integrin β7 expression. Our results demonstrate differences in T cell response magnitude, epitope specificity and phenotype between symptomatic and non-symptomatic peanut-sensitized patients. In addition to IgE reactivity, analysis of peanut-specific T cells may be useful to improve our understanding of different clinical manifestations in peanut allergy.


Clinical and economic outcomes of pharmacist-managed antimicrobial prophylaxis in surgical patients.
The associations between pharmacist-managed antimicrobial prophylaxis in Medicare patients who had surgical codes indicative of the need for antimicrobial prophylaxis and the major health care outcomes of death rate, length of stay, Medicare charges, drug charges, laboratory charges, and complications were explored. Pharmacist management of antimicrobial prophylaxis was evaluated in 242,704 Medicare patients from 860 [corrected] hospitals. Patients who developed a surgical-site infection (SSI) had a 331.58% increased risk of death compared with patients who did not develop an SSI (chi2 = 743.471; df = 1; p < 0.0001; odds ratio [OR], 3.62; 95% confidence interval [CI], 3.28-3.99). Patients who developed an SSI also had a 167.16% increase in length of stay, 136.49% increase in total Medicare charges, 245.96% increase in drug charges, and 187.14% increase in laboratory charges. In hospitals without pharmacist-managed antimicrobial prophylaxis, death rates were 52.06% higher (105 excess deaths; p < 0.0001; OR, 1.54; 95% CI, 1.46-1.63), length of stay was 10.21% higher (167,941 excess patient days, p < 0.0001), mean +/- S.D. total Medicare charges were 3.10% higher ($980 +/- $1,109 more per patient) ($182,113,400 excess total Medicare charges, p < 0.0001), mean +/- S.D. drug charges were 7.24% higher ($292 +/- $492 more per patient) ($54,262,360 excess drug charges, p = 0.005), mean +/- S.D. laboratory charges were 2.72% higher ($74 +/- $151 more per patient) ($13,751,420 excess laboratory charges, p = 0.0056), and SSIs were 34.30% higher (chi2 = 95.48; df = 1; p < 0.0001; OR, 1.52; 95% CI, 1.40-1.66). The provision of pharmacist-managed antimicrobial prophylaxis was associated with significant improvement in clinical and economic outcomes for Medicare patients with a surgical code indicative of the need for antimicrobial prophylaxis.


Alanine-scanning mutagenesis reveals a cytosine deaminase mutant with altered substrate preference.
Suicide gene therapy of cancer is a method whereby cancerous tumors can be selectively eradicated while sparing damage to normal tissue. This is accomplished by delivering a gene, encoding an enzyme capable of specifically converting a nontoxic prodrug into a cytotoxin, to cancer cells followed by prodrug administration. The Escherichia coli gene, codA, encodes cytosine deaminase and is introduced into cancer cells followed by administration of the prodrug 5-fluorocytosine (5-FC). Cytosine deaminase converts 5-FC into cytotoxic 5-fluorouracil, which leads to tumor-cell eradication. One limitation of this enzyme/prodrug combination is that 5-FC is a poor substrate for bacterial cytosine deaminase. The crystal structure of bacterial cytosine deaminase (bCD) reveals that a loop structure in the active site pocket of wild-type bCD comprising residues 310-320 undergoes a conformational change upon cytosine binding, making several contacts to the pyrimidine ring. Alanine-scanning mutagenesis was used to investigate the structure-function relationship of amino acid residues within this region, especially with regard to substrate specificity. Using an E. coli genetic complementation system, seven active mutants were identified (F310A, G311A, H312A, D314A, V315A, F316A, and P318A). Further characterization of these mutants reveals that mutant F316A is 14-fold more efficient than the wild-type at deaminating cytosine to uracil. The mutant D314A enzyme demonstrates a dramatic decrease in cytosine activity (17-fold) as well as a slight increase in activity toward 5-FC (2-fold), indicating that mutant D314A prefers the prodrug over cytosine by almost 20-fold, suggesting that it may be a superior suicide gene.


Nanoscale organization of CaV2.1 splice isoforms at presynaptic terminals: implications for synaptic vesicle release and synaptic facilitation.
The distance between CaV2.1 voltage-gated Ca2+ channels and the Ca2+ sensor responsible for vesicle release at presynaptic terminals is critical for determining synaptic strength. Yet, the molecular mechanisms responsible for a loose coupling configuration of CaV2.1 in certain synapses or developmental periods and a tight one in others remain unknown. Here, we examine the nanoscale organization of two CaV2.1 splice isoforms (CaV2.1[EFa] and CaV2.1[EFb]) at presynaptic terminals by superresolution structured illumination microscopy. We find that CaV2.1[EFa] is more tightly co-localized with presynaptic markers than CaV2.1[EFb], suggesting that alternative splicing plays a crucial role in the synaptic organization of CaV2.1 channels.


Pharmacokinetics of pradefovir and PMEA in healthy volunteers after oral dosing of pradefovir.
The pharmacokinetics of pradefovir and adefovir, 9-(2-phosphonylmethoxyethyl) adenine (PMEA), was evaluated in healthy male volunteers after oral dosing of pradefovir (10, 30, or 60 mg). Pradefovir was absorbed rapidly. The maximum serum concentration, the area under the concentration-time curve between 0 and 96 hours after dosing (AUC(0-96)), and the area under the plasma concentration versus time curve from time 0 to infinity (AUC(0-infinity)) of pradefovir and PMEA increased with the dose of pradefovir. The ratio of PMEA to pradefovir for AUC(0-96) and AUC(0-infinity) ranged from 1.4 to 1.8. Renal clearance of pradefovir (18-31 L/h) increased with the dose of pradefovir and was greater than glomerular filtration. The fraction of total body clearance due to renal clearance was low (0.045 to 0.083), suggesting that metabolic clearance played a significant role in the clearance of pradefovir in man. In addition, an evaluation of the food effect was conducted at the 30-mg dose. The results indicate that food intake has no effect on the extent of exposure of pradefovir and PMEA but may decrease the rate of systemic availability of PMEA.


Structural changes in Clostridium botulinum type E after treatment with boticin S5 1 .
Treatment with boticin S5(1), a bacteriocin produced by a nontoxigenic organism closely related to Clostridium botulinum type E, caused extensive changes in the structure of a sensitive C. botulinum type E strain. Nucleoid deoxyribonucleic acid, normally seen as fine filaments scattered throughout the cell, was aggregated into dense deoxyribonucleic acid masses. Mesosomes appeared to undergo structural rearrangement from lamellar to vesicular configuration. Eventual dissolution of cell contents left bacterial ghosts composed of seemingly intact cell walls with remnants of the cytoplasmic membrane and internal structures. The morphological changes observed in boticin-treated strain 070 cells were very similar to those produced by a bacteriocin-like substance from phage type 71 Staphylococcus aureus on sensitive beta-hemolytic streptococci. A similarity in the mode of action of the two bactericidal agents is suggested.


New Selective Grass Herbicides and Their Hydrolytic Properties as Pro-herbicides.
New derivatives of pyridinyloxyphenoxypropionic acid were synthesizd, which have a keto group in their ester-alkyl structures. Some acylmethyl esters, e.g., acetylmethyl ester, hydroxyacetylmethyl ester and diazoacetylmethyl ester, were found to show outstanding herbicidal activity against grass weeds. A study of the hydrolysis rate of esters with regard to their pro-herbicide action is also discussed.


Mechanisms of Light-induced Liposome Permeabilization.
Liposomes have been widely studied for drug delivery applications. The inclusion of photoactive molecules into liposomes opens the possibility of light-controlled cargo release to enhance drug biodistribution or bioavailability at target sites. Membrane permeabilization induced by light can be an effective strategy for enhancing cargo delivery with spatial and temporal control, which holds potential for chemophototherapy approaches. Several diverse mechanisms have been reported including light-induced oxidation, photocrosslinking, photoisomerization, photocleavage and photothermal release. Here, we review selected recent reports of light-triggered cargo release from liposomes.


Calcitonin gene-related peptide can attenuate or augment pancreatic damage in caerulein-induced pancreatitis in rats.
We have recently shown that treatment with calcitonin gene-related peptide (CGRP) before and during induction of acute pancreatitis exhibits a protective effect against pancreatic damage evoked by overdose of caerulein. Studies in the stomach have shown that administration of CGRP exhibits dual action on gastric mucosa, CGRP administration before induction of gastric lesions, protects gastric mucosa against damage, whereas treatment with this peptide after development of gastric ulcer exacerbates mucosal injury. These observations prompt us to determine the influence of CGRP administrated before and after induction of pancreatitis on development and evolution of pancreatic tissue damage. Acute pancreatitis was induced by s.c. infusion of caerulein (10 microg/kg/h) for 5 h. CGRP was administrated (10 microg/kg s.c. per dose) 30 min prior to caerulein infusion and 3 h later during caerulein infusion or at the time 1 h, 4 h and 7 h after the end of caerulein infusion. Rats were sacrificed at the time 0 h, 3 h or 9 h after cessation of caerulein administration. The pancreatic blood flow (PBF), plasma activity of amylase, plasma interleukin-1beta concentration, cell proliferation, biochemical and morphological signs of pancreatitis were examined. Caerulein-induced pancreatitis (CIP) led to 42% decrease in DNA synthesis, 30% inhibition of PBF, as well as, a significant increase in pancreatic weight, plasma amylase activity, plasma interleukin-1beta concentration, and development of the histological signs of pancreatic damage (edema, leukocyte infiltration and vacuolization). Treatment with CGRP prior and during induction of CIP attenuated the pancreatic damage what was manifested by partial reversion of the drop in DNA synthesis (40.9+1.7 v. 34.2+2.0 dpm/microg DNA) and PBF (83+3% v. 70+3%). Increases in pancreatic weight and plasma interleukin-1beta were reduced. Morphology showed improvement of pancreatic integrity. Administration of CGRP after induction of CIP aggravated pancreatic damage what was manifested by additional decrease in PBF and DNA synthesis. Also pancreatic weight as well as histological signs of pancreatic damage were increased. (1) Administration of CGRP before and during induction of pancreatitis protects pancreas against pancreatic damage. (2) Treatment with CGRP after development of CIP aggravates pancreatic damage.


Malignant blue naevus with distant subcutaneous metastasis.
Malignant blue naevus is a distinct but rarely documented variant of malignant melanoma, and we describe the triple recurrence of a suprapatellar cellular blue naevus over 12 years in a middle-aged woman. Staging investigations revealed a distant subcutaneous metastasis of the right thigh. Immunohistochemistry of the primary lesion and all recurrences showed S-100, HMB-45, NKI/C-3 and Ki-67 positive cells. However, non-malignant cellular blue naevi from five consecutive other patients were all Ki-67 negative. The change from negative to positive Ki-67 responsivity may therefore be a valuable marker of malignant and metastatic potential in early cellular blue naevi.


Ranking solvent interactions and dielectric constants with [Pt(mesBIAN)(tda)]: A cautionary tale for polarity determinations in ionic liquids.
The solvatochromic properties of [Pt(mesBIAN)(tda)] are studied in traditional molecular solvents and ionic liquids and duly compared along established empirical solvent parameter scales. The charge-transfer absorption band of [Pt(mesBIAN)(tda)] is determined to be primarily dependent upon solvent acidity and dipolarity. Notably, ionic liquids do not obey the same well-behaved trend as molecular solvents, highlighting the complexity and domain (nano)segregation inherent to ionic liquids.


Light intensity and housing for pigeons.
Four light intensities were used in completely enclosed pigeon housed for 14 hours per 24 hours. Open front pens with only natural light were also used. There were four pens per treatment and five pairs of young, breeding age, White Carneaux per pen for 420 days. Results per treatment, 16, 30, 44 and 61 lumens per sq. m. and open pens, were respectively as follows for each objective: squabs raised-252, 220, 288, 203, and 212 with no significant differences except for the 44 lumen treatment which was higher than all others except 16; body wt./squab in g.-522, 526, 522, 508, and 531 at four weeks of age with no significant differences; feed per squab in kg.-4.7, 5.3, 4.5, 5.5, and 5.1 with only a significant difference between treatments 44 and 61 lumens; percent hatchability-89.7, 82.1, 89.6, 78.0, and 82.9 with no significant differences; percent squabs raised-93.7, 88.7, 97.9, 91.0, and 89.5 with no significant differences. The average number of squabs raised per treatment for all enclosed artifically lighted pens was 241 compared to 212 for the open pens with only natural light.


The psychosocial impact of infertility.
I would like to conclude this article by making a special appeal to nurses and related health care professionals to appreciate the special needs of the infertile couple. In being denied a pregnancy and parenting experience when they truly desire it, they are faced with a life crisis of major proportions. It is the goal of the person who counsels infertile couples to help them resolve the crisis positively, and to develop new insights and strengths as a result. The infertile couple who so earnestly desire a family deserve respect and attention. They should be seen as having a legitimate health problem which has attendant emotional issues and overtones. Though they are rarely physically ill and do not usually find themselves incapable of performing their work and living functions, this neglected population suffers an enormous toll in the quality of their life. Health care professionals must be aware of the special feelings and issues of the infertile couple.


Prenatal growth in humans and postnatal brain maturation into late adolescence.
Prenatal life encompasses a critical phase of human brain development, but neurodevelopmental consequences of normative differences in prenatal growth among full-term pregnancies remain largely uncharted. Here, we combine the power of a within-monozygotic twin study design with longitudinal neuroimaging methods that parse dissociable components of structural brain development between ages 3 and 30 y, to show that subtle variations of the in utero environment, as indexed by mild birth weight (BW) variation within monozygotic pairs, are accompanied by statistically significant (i) differences in postnatal intelligence quotient (IQ) and (ii) alterations of brain anatomy that persist at least into late adolescence. Greater BW within the normal range confers a sustained and generalized increase in brain volume, which in the cortical sheet, is specifically driven by altered surface area rather than cortical thickness. Surface area is maximally sensitive to BW variation within cortical regions implicated in the biology of several mental disorders, the risk for which is modified by normative BW variation. We complement this near-experimental test of prenatal environmental influences on human brain development by replicating anatomical findings in dizygotic twins and unrelated singletons. Thus, using over 1,000 brain scans, across three independent samples, we link subtle differences in prenatal growth, within ranges seen among the majority of human pregnancies, to protracted surface area alterations, that preferentially impact later-maturing associative cortices important for higher cognition. By mapping the sensitivity of postnatal human brain development to prenatal influences, our findings underline the potency of in utero life in shaping postnatal outcomes of neuroscientific and public health importance.


Airway metabolic profiling during Streptococcus pneumoniae infection identifies branched chain amino acids as signatures of upper airway colonisation.
Streptococcus pneumoniae is a leading cause of community-acquired pneumonia and bacteraemia and is capable of remarkable phenotypic plasticity, responding rapidly to environmental change. Pneumococcus is a nasopharyngeal commensal, but is responsible for severe, acute infections following dissemination within-host. Pneumococcus is adept at utilising host resources, but the airways are compartmentalised and those resources are not evenly distributed. Challenges and opportunities in metabolite acquisition within different airway niches may contribute to the commensal-pathogen switch when pneumococcus moves from nasopharynx into lungs. We used NMR to characterise the metabolic landscape of the mouse airways, in health and during infection. Using paired nasopharynx and lung samples from naïve animals, we identified fundamental differences in metabolite bioavailability between airway niches. Pneumococcal pneumonia was associated with rapid and dramatic shifts in the lung metabolic environment, whilst nasopharyngeal carriage led to only modest change in upper airway metabolite profiles. NMR spectra derived from the nasopharynx of mice infected with closely-related pneumococcal strains that differ in their colonisation potential could be distinguished from one another using multivariate dimensionality reduction methods. The resulting models highlighted that increased branched-chain amino acid (BCAA) bioavailability in nasopharynx is a feature of infection with the high colonisation potential strain. Subsequent analysis revealed increased expression of BCAA transport genes and increased intracellular concentrations of BCAA in that same strain. Movement from upper to lower airway environments is associated with shifting challenges in metabolic resource allocation for pneumococci. Efficient biosynthesis, liberation or acquisition of BCAA is a feature of adaptation to nasopharyngeal colonisation.


CO adsorption on MgO thin-films: formation and interaction of surface charged defects.
Two-dimensional (2D) materials formed by thin-films of metal oxides that grow on metal supports are commonly used in heterogeneous catalysis and multilayer electronic devices. Despite extensive research on these systems, the effects of charged defects at supported oxides on surface processes are still not clear. In this work, we perform spin-polarized density-functional theory (DFT) calculations to investigate formation and interaction of charged magnesium and oxygen vacancies, and Al dopants on MgO(001)/Ag(001) surface. The results show a sizable interface compressive effect that decreases the metal work function as electrons are added on the MgO surface with a magnesium vacancy. This surface displays a larger formation energy in a water environment (O-rich condition) even with additional Al-doping. Under these conditions, we found that a polar molecule such as CO is more strongly adsorbed on the low-coordination oxygen sites due to a larger contribution of the channeled electronic transport with the silver interface regardless of the surface charge. Therefore, these findings elucidate how surface intrinsic vacancies can influence or contribute to charge transfer, which allows one to explore more specific reactions at different surface topologies for more efficient catalysts for CO2 conversion.


A Study of the Variation in the Salivary Peptide Profiles of Young Healthy Adults Acquired Using MALDI-TOF MS.
A cross-sectional observational study was conducted to evaluate the inter-individual variation in the MALDI-TOF MS peptide profiles of unstimulated whole saliva in a population of 268 systemically healthy adults aged 18-30 yr (150 males and 118 females) with no apparent caries lesions or periodontal disease. Using Spectral Clustering, four subgroups of individuals were identified within the study population. These subgroups were delimited by the pattern of variation in 9 peaks detected in the 2-15 kDa m/z range. An Unsupervised Feature Selection algorithm showed that P-C peptide, a 44 residue-long salivary acidic proline-rich protein, and three of its fragments (Fr. 1-25, Fr. 15-35 and Fr. 15-44) play a central role in delimiting the subgroups. Significant differences were found in the salivary biochemistry of the subgroups with regard to lysozyme and chitinase, two enzymes that are part of the salivary innate defense system (p < 0.001). These results suggest that MALDI-TOF MS salivary peptide profiles may relate information on the underlying state of the oral ecosystem and may provide a useful reference for salivary disease biomarker discovery studies.


Bumpy road to the diagnosis of polycythaemia vera.
Polycythaemia vera (PV) is the most common myeloproliferative neoplasm, characterised by increased red cell mass that can present as an unspecified symptom or a thrombohaemorrhagic event. Its diagnosis is based on the presence of erythrocytosis, the identification of the Janus kinase 2 mutation and bone marrow aspirate or biopsy alterations. The challenge of this disease lies on the treatment approach. Its cornerstone is phlebotomy, but depending on the vascular risk, it can include cytoreductive agents, low-dose aspirin or even anticoagulation. We present the case of a 75-year-old woman, whose inaugural presentation of PV was an arterial peripheral occlusion followed by three recurrent events in the same arterial region and a pulmonary embolism. A phlebotomy was initially performed and, after the diagnosis was made, the patient was initiated on low-dose aspirin and anticoagulation with favourable outcome.


Vacuum-Assisted Therapy for Combined Volar-Dorsal Soft-Tissue Defects of the Hand: A Case Report.
Application of negative-pressure wound therapy dressings to the web spaces and small, often moist, areas of the hand can be technically demanding and time consuming. The researchers present a case report and technique for managing a devastating hand infection and soft-tissue defects by creating a self-fabricated sponge glove that is easily reproducible. Vacuum-assisted therapy for combined volar dorsal soft-tissue defects of the hand, or "Hand Vac," is a novel approach for treating extensive hand wounds. This technique was used in a patient with diabetes with a deep space infection of the hand following serial debridements and antibiotic bead therapy. A single, medium-size sponge was cut using a knife and scissors to create an easily applied glove that was then sealed with adhesive dressing and a single suction port. The patient avoided complete amputation of the hand and deep infection was eradicated. The wounds had progressive granulation and healing and were eventually covered with split-thickness skin grafts. The authors conclude that severe soft-tissue defects involving both the volar and dorsal aspects of the hand can be effectively managed with a single glove-like sponge and suction port.


Quantum transport in graphene nanoribbons: effects of edge reconstruction and chemical reactivity.
We present first-principles transport calculations of graphene nanoribbons with chemically reconstructed edge profiles. Depending on the geometry of the defect and the degree of hydrogenation, spectacularly different transport mechanisms are obtained. In the case of monohydrogenated pentagon (heptagon) defects, an effective acceptor (donor) character results in strong electron-hole conductance asymmetry. In contrast, weak backscattering is obtained for defects that preserve the benzenoid structure of graphene. Based on a tight-binding model derived from ab initio calculations, evidence for large conductance scaling fluctuations are found in disordered ribbons with lengths up to the micrometer scale.


Long non-coding RNA HOTAIR up-regulates chemokine (C-C motif) ligand 2 and promotes proliferation of macrophages and myeloid-derived suppressor cells in hepatocellular carcinoma cell lines.
Accumulating evidence demonstrated that Hox antisense intergenic RNA (HOTAIR) serves essential roles in the development and metastasis of several types of cancer. In hepatocellular carcinoma (HCC), high expression of HOTAIR is associated with poor prognosis, and HOTAIR regulates cell migration and proliferation. However, the downstream molecular targets of HOTAIR depend on the cancer cell types, and little is known about the precise molecular mechanisms of HOTAIR involved in cancer development. The present study investigated the role of HOTAIR in HCC cell lines. Notably, the overexpression of HOTAIR in HCC cell lines did not affect cell migration and proliferation capability. In the microarray analysis, C-C motif chemokine ligand (CCL)2 was identified to be differentially expressed in HOTAIR-overexpressing cells, and it was confirmed that HOTAIR promotes the secretion of CCL2. Furthermore, it was revealed that the proportion of macrophages and myeloid-derived suppressor cells (MDSCs) were increased when peripheral blood mononuclear cells were co-cultured with HOTAIR-overexpressing cells. Collectively, these data suggest that HOTAIR regulates CCL2 expression, which may be involved in the recruitment of macrophages and MDSCs to the tumor microenvironment.


Growth factors in milk.
The paper outlines well recognized growth factors in milk (colostrum and during lactation) like the IGF-family; epidermal growth factor; transforming growth factors a, beta; tumor necrosis factor; basic fibroblast growth factor and platelet derived growth factor The origin of these factors is discussed. The IGF-family may be of greater benefit to the newborn calf in contrast to other species where EGF seems to be the dominating and important factor. However, the primary role of the measured growth factors may be related more to the proliferation and maintenance of the lactating gland itself.


Enduring sleep complaints predict health problems: a six-year follow-up of the survey of health and retirement in Europe.
Sleep complaints are common and enduring among old people. The study aimed to extend current knowledge by exploring the effects of episodic versus chronic sleep complaints on a range of physical and mental health outcomes. Older adults (N = 8934, mean age = 64) who participated in Waves 1, 2 and 4 of the Survey of Health, Ageing and Retirement in Europe (SHARE) reported sleep and health outcome measures. Episodic sleep complaints, in the first or in the second wave and chronic sleep complaints, in both waves were recorded. Outcomes in Wave 4 included physical symptoms, difficulties in activities of daily living and low quality of life. Logistic regressions examined whether episodic and chronic sleep complaints at W1 and W2 predict W4 health outcomes. Chronic sleep complaints predicted worse outcomes, compared to no sleep difficulties and to episodic sleep complaints, even after adjusting for demographic characteristics and previous levels of health. Sleep complaints and mainly chronic sleep complaints are related to elevated risk of future health and functional problems. Caregivers are encouraged to address sleep complaints and provide their older patients with help before sleep complaints become persistent.


Towards effective emerging infectious disease surveillance.
In this plenary talk given at the annual meeting of the Association for Politics and the Life Sciences at Texas Tech University last October, Professor Sophal Ear, then of the U.S. Naval Postgraduate School in Monterey, discussed his research on the political economy of emerging infectious disease (EID) surveillance programs. His talk reviews lessons learned for U.S. military medical research laboratories collaborating with developing countries and is comprised of three case studies: Cambodia (U.S. Naval Area Medical Research Unit 2 or NAMRU-2), Indonesia (also NAMRU-2 in the context of H5N1 or Highly Pathogenic Avian Influenza), (1) and Mexico (that country's handling of A/H1N1 or Swine Flu in 2009). (2) Professor Ear's research provides policymakers with tools for improving the effectiveness of new or existing EID surveillance programs. His work also offers host countries the opportunity to incorporate ideas, provide opinions, and debate the management of political and economic constraints facing their programs. In this analysis, constraints are found for each case study and general recommendations are given for improving global emerging infectious disease surveillance across political, economic, and cultural dimensions.


How much uncompensated care do doctors provide?
The magnitude of provider uncompensated care has become an important public policy issue. Yet existing measures of uncompensated care are flawed because they compare uninsured payments to list prices, not to the prices actually paid by the insured. We address this issue using a novel source of data from a vendor that processes financial data for almost 4000 physicians. We measure uncompensated care as the net amount that physicians lose by lower payments from the uninsured than from the insured. Our best estimate is that physicians provide negative uncompensated care to the uninsured, earning more on uninsured patients than on insured patients with comparable treatments. Even our most conservative estimates suggest that uncompensated care amounts to only 0.8% of revenues, or at most $3.2 billion nationally. These results highlight the important distinction between charges and payments, and point to the need for a re-definition of uncompensated care in the health sector going forward.


[Interaction between strychnine and bovine serum albumin].
To study the interaction between strychnine and bovine serum albumin. Fluorescence spectroscopy and ultraviolet spectroscopy were used. The static quenching and the non-radiation energy transfer are the two main reasons to leading the fluorescence quenching of BSA. The apparent combining constants (K(A)) between strychnine and BSA are 3.72 x 10(3) at 27 degrees C, 4.27 x 10(3) at 37 degrees C, 4.47 x 10(3) at 47 degrees C and the combining sites are 1.01 +/- 0.03. The combining distance (r = 3.795 nm) and energy transfer efficiency (E = 0.0338) are obtained by Förster's non-radiation energy transfer mechanism. The interaction between strychnine and BSA was driven mainly by hydrophobic force.


Nuclear envelope assembly relies on CHMP-7 in the absence of BAF-LEM-mediated hole closure.
Barrier-to-autointegration factor (BAF) is a DNA binding protein that crosslinks chromatin to assemble the nuclear envelope (NE) after mitosis. BAF also binds the Lap2b-Emerin-Man1 (LEM) domain family of NE proteins to repair interphase ruptures. The NE adaptors to ESCRTs, LEMD2-CHMP7, seal NE holes surrounding mitotic spindle microtubules (MTs), but whether NE hole closure in mitosis involves BAF-LEM binding is not known. Here, we analyze NE sealing after meiosis II in C. elegans oocytes to show that BAF-LEM binding and LEM-2 LEMD2 -CHMP-7 have distinct roles in hole closure around spindle MTs. LEM-2/EMR-1 emerin function redundantly with BAF-1 to seal the NE. Compromising BAF-LEM binding revealed an additional role for EMR-1 in maintenance of the NE permeability barrier and an essential role for LEM-2-CHMP-7 in preventing NE assembly failure. The WH domain of LEM-2 recruits the majority of CHMP-7 to the NE in C. elegans and a LEM-2 -independent pool of CHMP-7, which is mostly enriched in the nucleoplasm, also contributes to NE stability. Thus, NE hole closure surrounding spindle MTs requires redundant mechanisms that safeguard against failure in NE assembly to support embryogenesis.


Comprehensive comparison between geriatric and nongeriatric patients with trauma.
The incidence of geriatric trauma is increasing due to the growing elderly population. Healthcare providers require a global perspective to differentiate critical factors that might alter patients' prognosis.We retrospectively reviewed all adult patients admitted to a trauma center during a 4-year period. We identified 655 adult trauma patients aged from 18 to 64 (nongeriatric group) and 273 trauma patients ≥65 years (geriatric group). Clinical data were collected and compared between the 2 groups.The geriatric group had a higher incidence of trauma and higher Injury Severity Scores than did the nongeriatric group. Fewer geriatric patients underwent surgical treatment (all patients: geriatric vs nongeriatric: 65.9% vs 70.7%; patients with severe trauma: geriatric vs nongeriatric: 27.6% vs 44.5%). Regarding prognosis, the geriatric group exhibited higher mortality rate and less need for long-term care (geriatric vs nongeriatric: mortality: 5.5% vs 1.8%; long-term care: 2.2% vs 5.0%).We observed that geriatric patients had higher trauma incidence and higher trauma mortality rate. Aging is a definite predictor of poor outcomes for trauma patients. Limited physiological reserves and preference for less aggressive treatment might be the main reasons for poor outcomes in elderly individuals.


Selective demonstration by tannic acid of a special cytoplasmic tubular system in the chloride cells of teleost gills.
Chloride cells in gill filaments in the fresh-water catfish (Parasilurus asotus) were examined by electron microscopy, using a tannic acid-glutaraldehyde fixative before osmification. This method allows clear demarcation of the cell surfaces through enhanced contrast and electron density. In the cytoplasm of chloride cells, only those tubules continuous with the cell surfaces--especially the outer leaflet of their membranes--remarkably increase in electron density. The cytoplasm of cells other than chloride cells, however, remains unaffected by the tannic acid treatment. The present study suggests that the use of tannic acid is advantageous for selective demonstration of the cell surfaces and their cytoplasmic derivatives.


Safety and immunogenicity of inactivated varicella-zoster virus vaccine in adults with hematologic malignancies receiving treatment with anti-CD20 monoclonal antibodies.
Immunocompromised patients can experience significant morbidity and occasional mortality from complications associated with herpes zoster (HZ), but live attenuated HZ vaccine is contraindicated for these patients. Inactivated zoster vaccine (ZVIN) is in development for prevention of HZ in immunocompromised patients. However, there are limited data in the literature regarding the effect of anti-CD20 monoclonal antibodies on vaccine-related cell-mediated immune response. This study evaluated safety and immunogenicity of ZVIN in patients with hematologic malignancies (HM) receiving anti-CD20 monoclonal antibodies (alone or in combination chemotherapy regimens) and not likely to undergo hematopoietic cell transplant (HCT) (n=80). This was an open-label, single-arm, multicenter Phase I study (NCT01460719) of a 4-dose ZVIN regimen (∼30days between doses) in patients ⩾18years old. Blood samples were collected prior to dose 1 and 28days Postdose 4 to measure varicella zoster virus (VZV)-specific T-cell responses using interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT). The primary hypothesis was that ZVIN would elicit significant VZV-specific immune responses at ∼28days Postdose 4, with a geometric fold rise (GMFR) >1.0. All vaccinated patients were evaluated for adverse events (AE) through 28days Postdose 4. ZVIN elicited a statistically significant VZV-specific immune response measured by IFN-γ ELISPOT at 28days Postdose 4 (GMFR=4.34 [90% CI:3.01, 6.24], p-value<0.001), meeting the pre-specified success criterion. Overall, 85% (68/80) of patients reported ⩾1 AE, 44% (35/80) reported ⩾1 injection-site AE, and 74% (59/80) reported ⩾1 systemic AE. The majority of systemic AEs were non-serious and considered unrelated to vaccination by the investigator. Frequencies of AEs did not increase with subsequent doses of vaccine. No recipient of ZVIN had rash polymerase chain reaction (PCR) positive for VZV vaccine strain. In adults with HM receiving anti-CD20 monoclonal antibodies, ZVIN was well-tolerated and elicited statistically significant VZV-specific T-cell responses ∼28days Postdose 4. CLINICALTRIALS.GOV identifier: NCT01460719.


Hydrodissection for the Treatment of Vascular Thoracic Outlet Syndrome.
The following case explores the effectiveness of a new treatment modality for vascular thoracic outlet syndrome (vTOS). Few conservative treatments exist to alleviate symptoms of vTOS. In this case, a 25-year-old male was diagnosed with vTOS four months prior to presentation. A combination of poor posture, inactivity, and protruding screws from a prior clavicle fracture repair were compromising the subclavicular vasculature. Symptoms of claudication and a cold right arm/hand led the patient to seek medical treatment. Post failed physiotherapy and pharmacotherapy, the vascular surgeon advised for surgery. He was hesitant to undergo major surgical intervention; therefore, after exploring possible remedies, hydrodissection was chosen for its potential merit in this case. After hydrodissection was performed to decompress the subclavicular neurovascular bundle, the patient reported immediate alleviation of his symptoms. Post two-week and three-month follow-up, there was complete resolution of symptoms with no recurrence. Although there is a lack of literature supporting the use of hydrodissection to treat vTOS, this was a specific case in which hydrodissection demonstrated to be an effective treatment modality. The specific utilization of hydrodissection should be further studied to increase the literature base and increase awareness of its potential effectiveness for this and similar conditions.


Improvement in refractory heart failure by nephrectomy for renal tumour.
Hypoalbuminaemia and anaemia are conditions known to aggravate congestive cardiac failure (CCF). Renal cell carcinoma is often associated with hypoalbuminaemia and anaemia. The authors report an interesting case of a patient with severe refractory CCF who incidentally was found to have a massive renal cell tumour. Clinically, his heart failure was being aggravated by hypoalbuminaemia and anaemia. Despite aggressive diuretic therapy and multiple blood and albumin transfusions, there was no clinical improvement. He subsequently underwent nephrectomy of the renal tumour, with subsequent dramatic clinical improvement in his heart failure. His symptoms resolved completely and he did not require any further diuretic therapy.


Does the expression of fascin-1 and tumor subclassification help to assess the risk of recurrence and progression in t1 urothelial urinary bladder carcinoma?
To evaluate the prognostic value of T1 subclassification and fascin-1 expression in T1 human urothelial cell carcinoma of the bladder. In a prospective study with 105 consecutive patients, T1 tumors were subclassified into 2 groups according to the depth of tumor invasion. The tunica muscularis mucosae was used as a landmark. The expression of fascin-1 was examined by using an anti-fascin-1 mouse monoclonal antibody and was evaluated semiquantitatively for both intensity and distribution. The patients were followed up for 27.3 +/- 13.7 months. The T1 tumor subclassification was feasible in 99 patients (94%). T1a tumor was detected in 77 patients (73%), T1b tumor in 22 patients (21%). An invasive tumor was found in 5 patients (4.8%) during the restaging transurethral resection of the bladder. The risk of understaging in patients with T1b tumor was 18%. There was not a significant difference in time to the recurrence in the T1a and the T1b group. The progression-free survival rates were significantly different between both groups (p = 0.0034). No correlation was found between fascin-1 positivity and the depth of tumor invasion. Fascin-1 positivity did not correlate with recurrence or the progression-free intervals. In the multivariate analysis, only the extent of lamina propria invasion was an independent predictor of the tumor progression. The fascin positivity was not an independent prognostic factor relating to the risk of recurrence or progression. The finding of T1b tumor was connected with a significantly higher risk of progression and understaging. The fascin-1 expression did not correlate with the depth of tumor invasion or with the tumor recurrence or progression.


The price of alcohol: a consideration of contextual factors.
The current study considers the determinants of prices charged for alcoholic beverages by on-premise and off-premise outlets in Alaska. Alcohol outlet densities, a surrogate measure for local retail competition, are expected to be negatively associated with prices while costs associated with distribution are expected to be positively related to prices. Community demographic and economic characteristics may affect observed local prices via the level of demand, retail costs borne by retailers, or the quality of brands offered for sale. The core data for these analyses came from a telephone survey of Alaskan retail establishments licensed to serve alcohol. This survey utilized computer-assisted telephone interviewing (CATI) techniques to collect alcohol-pricing information from on-premise (i.e., establishments where alcohol is consumed at the point of purchase such as bars and restaurants) and off-premise (i.e., establishments such as grocery stores and convenience markets where consumption occurs in other locations) alcohol retailers throughout the state of Alaska. Price estimates were developed for each beverage-type based on alcohol content. Separate regression analyses were used to model each of the 8 price indices (on-premise and off-premise measures for beer, spirits, wine, and the average price across beverage types). All regressions also controlled for a set of zip-code level indicators of community economic and demographic characteristics based on census data. Outlet density per roadway mile was unrelated to price for both on- and off-premise establishments, either across or between beverage types. In contrast, overall distribution costs did appear to be related to alcohol price. The demographic and economic variables, as a group, were significantly related to observed prices. More attention needs to be directed to the manner in which sellers and buyers behave relative to alcoholic beverages. Alcohol demand remains responsive to prices; yet, consumers have considerable latitude in determining the price that they pay for alcohol.


On parameter estimation of chaotic systems via symbolic time-series analysis.
Symbolic time-series analysis is used for estimating the parameters of chaotic systems. It is assumed that a "target model" (i.e., a discrete- or continuous-time description of the data-generating mechanism) is available, but with unknown parameters. A time series, i.e., a noisy, finite sequence of a measured (output) variable, is given. The proposed method first prescribes to symbolize the time series, i.e., to transform it into a sequence of symbols, from which the statistics of symbols are readily derived. Then, a symbolic model (in the form of a Markov chain) is derived from the data. It allows one to predict, in a probabilistic fashion, the time evolution of the symbol sequence. The unknown parameters are derived by matching either the statistics of symbols, or the symbolic prediction derived from data, with those generated by the (parametrized) target model. Three examples of application (the Henon map, a population model, and the Duffing system) prove that satisfactory results can be obtained even with short time series.


Adolescent sexuality and disability.
All human beings are sexual from birth to death and all adolescents, with or without chronic illness or disability, must incorporate appropriate concepts of sexuality into their process of development from child to adult. This chapter reviews normal adolescent development with specific reference to sexuality. Potential effects of chronic illness and disability on this process are reviewed, including coital behavior, sexual abuse, sexual dysfunction, and sexual offending. Management of sexual issues in chronically ill or disabled adolescents is considered, including comments about gynecologic needs of disabled girls.


"Cold-sensitive" mutants of the Lac repressor.
Thirteen of more than 4,000 single-amino-acid-replacement mutants of the Lac repressor, generated by suppression of amber nonsense mutants, were characterized as having a cold-sensitive phenotype. However, when expressed as missense mutations, none of the replacements cause cold sensitivity, implicating the suppression mechanism as being responsible for this phenotype.


Counselor competence for telephone Motivation Interviewing addressing lifestyle change among Dutch older adults.
Counselor competence in telephone Motivation Interviewing (MI) to change lifestyle behaviors in a primary care population was assessed using the Motivational Interviewing Treatment Integrity (MITI) rating system. Counselor behavior was evaluated by trained raters. Twenty minutes of a random sample of 336 MI sessions were coded representing 232 counselees. Ninety-four sessions (28%) were double coded to assess inter-rater agreement. The MI fidelity was examined by comparing the MI fidelity scores direction, empathy, spirit, % open questions, % complex reflections, reflections-to-questions ratio, % MI-adherent responses with the matching beginner proficiency MITI threshold. The inter-rater agreements for the MI fidelity summary scores were good (spirit, reflections-to-questions ratio), fair (empathy, % open questions, % MI-adherent responses) or poor (direction, % complex reflection). The MI fidelity scores for direction, empathy, spirit and the percentage of complex reflections exceeded the MITI threshold, but lower scores were found for the percentage of open questions, the reflections-to-questions ratio and the percentage of MI-adherent responses. In conclusion, evidence that MI was implemented was revealed. However, the inter-rater agreements scores and some fidelity scores leave room for improvement indicating that raters and counselors may need more ongoing training and feedback to achieve and maintain adequate competence. These findings apply to more complex skills (as rating complex reflections) in particular.


Parental Adverse Childhood Experiences and Resilience on Coping After Discharge.
Adults with a history of adverse childhood experiences (ACEs) (eg, abuse) have suboptimal health outcomes. Resilience may blunt this effect. The effect of parental ACEs (and resilience) on coping with challenges involving their children (eg, hospitalization) is unclear. We sought to quantify ACE and resilience scores for parents of hospitalized children and evaluate their associations to parental coping after discharge. We conducted a prospective cohort study at a children's hospital (August 2015-May 2016). Eligible participants were English-speaking parents of children hospitalized on the Hospital Medicine or Complex Services team. The ACE questionnaire measured the responding parent's past adversity (ACE range: 0-10; ≥4 ACEs = high adversity). The Brief Resilience Scale (BRS) was used to measure their resilience (range: 1-5; higher is better). The primary outcome was measured by using the Post-Discharge Coping Difficulty Scale via a phone call 14 days post-discharge (range: 0-100; higher is worse). Associations were assessed by using multivariable linear regression, adjusting for parent- and patient-level covariates. A total of 671 (81% of eligible parents) responded. Respondents were primarily women (90%), employed (66%), and had at least a high school degree (65%); 60% of children were white, 54% were publicly insured. Sixty-four percent of parents reported ≥1 ACE; 19% had ≥4 ACEs. The mean Brief Resilience Scale score for parents was 3.95. In adjusted analyses, higher ACEs and lower resilience were significantly associated with more difficulty coping after discharge. More parental adversity and less resilience are associated with parental coping difficulties after discharge, representing potentially important levers for transition-focused interventions.


Hepatitis B knowledge and practices among Cambodian American women in Seattle, Washington.
Southeast Asians have higher liver cancer rates than any other racial/ethnic group in the US. Approximately 80 percent of liver cancers are etiologically associated with hepatitis B virus (HBV) infection which is endemic in Southeast Asia. An in-person survey of Cambodian women (n = 320) was conducted in Seattle, Washington, during 1999. The questionnaire included items about HBV knowledge, beliefs, and practices. Prior to being provided with a description of the disease, only about one-half (56 percent) of our respondents had heard of HBV infection. Less than one-quarter (23 percent) of the study group thought that asymptomatic individuals can transmit the disease to others. Most thought that HBV infection can cause liver cancer (54 percent) and death (72 percent). However, a minority thought that infection can be lifelong (24 percent) and incurable (15 percent). Only 38 percent reported they had been serologically tested for HBV. Finally, of those who had been tested and thought they were susceptible, two-thirds (67 percent) had not been vaccinated. Lower levels of education were associated with lower levels of HBV knowledge and serologic testing. Our findings suggest that Cambodian immigrants have low levels of HBV knowledge, serologic testing, and vaccination; and demonstrate a need for targeted educational interventions aimed at reducing HBV-related liver cancer mortality among Southeast Asian communities.


Pediatric feeding and swallowing rehabilitation: An overview.
Children with neurological disabilities frequently have problems with feeding and swallowing. Such problems have a significant impact on the health and well-being of these children and their families. The primary aims in the rehabilitation of pediatric feeding and swallowing disorders are focused on supporting growth, nutrition and hydration, the development of feeding activities, and ensuring safe swallowing with the aim of preventing choking and aspiration pneumonia. Pediatric feeding and swallowing disorders can be divided into four groups: transient, developmental, chronic or progressive.This article provides an overview of the available literature about the rehabilitation of feeding and swallowing disorders in infants and children. Principles of motor control, motor learning and neuroplasticity are discussed for the four groups of children with feeding and swallowing disorders.


A Bayesian Network Analysis of the Efficacy of Scaffolds and Stem Cells in Spinal Cord Injury Treatment.
Novel scaffolds and stem cells are alternatives for the treatment of spinal cord injury (SCI), which causes life-long disability. However, there is a lack of synthesized evidence comparing different therapies. To examine the efficacy of various treatments in achieving locomotor recovery in SCI animals. The PubMed, Scopus and Web of Science databases were searched from inception to 21st May 2021. The data were extracted by one investigator under the surveillance of a referee according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement and stored in Microsoft Excel. All data were analysed using Bayesian network analysis with a consistency model. The selection was performed in strict accordance with the participant, intervention, comparison, outcome and study (PICOS) principle, as specifically stated in the methods section. A total of 387 eligible studies involving 11169 animals subjected to 5 different treatments were evaluated. Compared to placebo or no treatment, scaffolds (mean difference (MD), 2.04; 95% credible interval (CrI): 1.58 to 2.50), exosomes (MD, 3.46; 95% CrI: 3.07 to 3.86), stem cells (MD, 4.18; 95% CrI: 3.28 to 5.07), scaffolds in conjunction with stem cells (MD, 5.26; 95% CrI: 4.62 to 5.89), and scaffolds in conjunction with non-cell agents (MD, 4.88; 95% CrI: 4.21 to 5.54) led to significant recovery of locomotor function in SCI animals. No significant difference in the locomotor function score was observed between animals treated with stem cells and those treated with exosomes (MD, 0.71; 95% CrI: -0.25 to 3.05), between animals treated with scaffolds in conjunction with stem cells and those treated with scaffolds in conjunction with non-cell agents (MD, -0.38; 95% CrI: -1.24 to 0.49), or between animals treated with scaffolds in conjunction with non-cell agents and those treated with stem cells (MD, 0.71; 95% CrI: - 0.38 to 1.80). Significant differences in the efficacy of various therapies in SCI animals were observed, and transplantation of scaffolds in conjunction with non-cell agents, scaffolds in conjunction with stem cells, and stem cells should be considered over transplantation of exosomes or scaffolds alone. Even though transplantation of scaffolds alone promoted locomotor function recovery in SCI animals, its use should be discouraged.


Higher prevalence of metformin-induced vitamin B12 deficiency in sulfonylurea combination compared with insulin combination in patients with type 2 diabetes: a cross-sectional study.
Long-term and high-dose treatment with metformin is known to be associated with vitamin B12 deficiency in patients with type 2 diabetes. We investigated whether the prevalence of B12 deficiency was different in patients treated with different combination of hypoglycemic agents with metformin during the same time period. A total of 394 patients with type 2 diabetes treated with metformin and sulfonylurea (S+M group, n = 299) or metformin and insulin (I+M group, n = 95) were consecutively recruited. The vitamin B12 and folate levels were quantified using the chemiluminescent enzyme immunoassay. Vitamin B12 deficiency was defined as vitamin B12≤300 pg/mL without folate deficiency (folate>4 ng/mL). The mean age of and duration of diabetes in the subjects were 59.4±10.5 years and 12.2±6.7 years, respectively. The mean vitamin B12 level of the total population was 638.0±279.6 pg/mL. The mean serum B12 levels were significantly lower in the S+M group compared with the I+M group (600.0±266.5 vs. 757.7±287.6 pg/mL, P<0.001). The prevalence of vitamin B12 deficiency in the metformin-treated patients was significantly higher in the S+M group compared with the I+M group (17.4% vs. 4.2%, P = 0.001). After adjustment for various factors, such as age, sex, diabetic duration, duration or daily dose of metformin, diabetic complications, and presence of anemia, sulfonylurea use was a significant independent risk factor for B12 deficiency (OR = 4.74, 95% CI 1.41-15.99, P = 0.012). In conclusion, our study demonstrated that patients with type 2 diabetes who were treated with metformin combined with sulfonylurea require clinical attention for vitamin B12 deficiency and regular monitoring of their vitamin B12 levels.


Induction of Systemic Resistance against Cucumber mosaic virus in Arabidopsis thaliana by Trichoderma asperellum SKT-1.
Trichoderma asperellum SKT-1 is a microbial pesticide that is very effective against various diseases. Our study was undertaken to evaluate T. asperellum SKT-1 for induction of resistance against yellow strain of Cucumber mosaic virus (CMV-Y) in Arabidopsis plants. Disease severity was rated at 2 weeks post inoculation (WPI). CMV titre in Arabidopsis leaves was determined by indirect enzyme-linked immunosorbent assay (ELISA) at 2 WPI. Our results demonstrated that among all Arabidopsis plants treated with barley grain inoculum (BGI) of SKT-1 NahG and npr1 plants showed no significant reduction in disease severity and CMV titre as compared with control plants. In contrast, disease severity and CMV titre were significantly reduced in all Arabidopsis plants treated with culture filtrate (CF) of SKT-1 as compared with control plants. RT-PCR results showed increased expression levels of SA-inducible genes, but not JA/ET-inducible genes, in leaves of BGI treated plants. Moreover, expression levels of SA- and JA/ET-inducible genes were increased in leaves of CF treated plants. In conclusion, BGI treatment induced systemic resistance against CMV through SA signaling cascade in Arabidopsis plants. While, treatment with CF of SKT-1 mediated the expression of a majority of the various pathogen related genes, which led to the increased defense mechanism against CMV infection.


The sequence and correlation of the changes in several parameters of energy metabolism induced by ischemic insult in heart muscle.
Samples of myocardium with varying degrees of ischemia were obtained from subendo- and subepicardium of nonischemic, ischemic border and center zones of canine left ventricles to assess the sequence of rapid alterations of several parameters of energy metabolism induced by myocardial ischemia. Ischemia was induced by occluding the left anterior descending coronary artery. The contents of creatine phosphate (CP) and ATP decreased significantly. There was a significant accumulation of lactate. The redox potential (Eh) and phosphorylation potential (l') also decreased sharply, but only a slight decrease in energy charge (E.C.) was noted. A close correlation was found between ATP and total adenine nucleotide (r = 0.99). There were various degrees of linear correlation between other parameters, except for ATP (and total adenine nucleotide) and Pi, and CP and l', which were uncorrelated. The sequence of rapid alterations in the parameters of energy metabolism induced by ischemia was: (1) l' and CP, (2) Pi, ATP and Eh, and finally (3) lactate and E.C. A significant increase of the heart rate and a decline of the mean blood pressure and left ventricular pressure (LVP) were also observed in association with a slight change in the maximum rate of rise of the left ventricular pressure (dP/dtmax).


Role of oocyte position in establishment of anterior-posterior polarity in Drosophila.
The polarized microtubule cytoskeleton of the Drosophila oocyte directs the localization of the maternal determinants which establish the anterior-posterior (AP) axis of the embryo. Because the formation of this microtubule array is dependent on signals from the follicle cells that surround the oocyte, it has been proposed that AP polarity originates in the follicle cells. Here it is shown that the movement of the oocyte to the posterior of the egg chamber early in oogenesis determines AP polarity in the follicle cell layer, and also in the oocyte. Moreover, the generation of AP asymmetry requires signaling from the germ line to the soma and back again.


Fluorescein test in the prediction of viability of skin flaps on pigs.
The fluorescein test is widely used in clinical and experimental studies for prediction of the viability of skin flaps. A thorough search of the literature revealed that the accuracy of this test had never been studied. Therefore, this study was designed to evaluate the accuracy of the fluorescein test in predicting the viability of skin flaps. A total of 212 unipedicle porcine skin flaps were used in this study. Statistical analysis demonstrated that the surviving area of the flap was significant greater than the staining area of the flap. We suggest that caution be exercised when the fluorescein dye test is used to assess skin flap viability and that the test be used for an approximate indication and not for an accurate prediction of the surviving flap area.


Application of Agree II Instrument for Appraisal of Postpartum Hemorrhage Clinical Practice Guidelines in Bosnia and Herzegovina.
Federal Minister of Health and Minister of Health and Social Welfare of the Republika Srpska as a Governmental health authorities in Federation of Bosnia and Herzegovina (FBiH) and the Republika Srpska nominated/appointed health professionals as their representatives to a multidisciplinary Guidelines Adaptation Group (GAG). This group started with its work in September 2015. The main purpose of the guidelines development exercise is to develop guidelines with worldwide recognized methodology for clinical guidelines development and adaptation. At the end of this consultancy, GAG would have develop a clinical practice guideline on Postpartum hemorrhage (PPH) through the adaptation method, starting from published international clinical guidelines and adapting it according to the country specific requirements. During the process of identifying the best guideline for adaptation, the GAG had to pass several steps. One of the crucial steps was to identify the questions related to clinical practice and health policy for which answers are needed to be addressed by the guideline. These questions included relevant issues regarding the topic area such as diagnosis, prognosis, intervention, service delivery, and training. After that, six guidelines have been researched by the six members of the GAG to see if they answered the identified questions. Evaluating the methodological quality of the selected clinical guidelines was a second essential step before deciding which ones could best fit the needs and interests. AGREE II instrument has been chosen as methods for evaluating clinical guideline quality and appropriateness. Four appraisers conducted the assessment of each of the selected guidelines for PPH. All appraisers passed the training for the AGREE II instrument before conducting appraisals, as recommended by the AGREE collaboration. Each of the four guidelines was rated independently with the AGREE II tool by each appraiser. The highest score was obtained by the WHO recommendations for postpartum hemorrhage guidelines and each of four assessors recommended it to be adapted and further implemented. In spite of several serous attempts and two Agencies for quality improvement in BiH the whole process of guideline adaptation is still in the beginning and therefore the establishment of a strong connection with similar institutions and organizations from our region and the rest of the world is very important. Cooperation and collaboration across institutions and countries and key stakeholders have potential to significantly improve the validity and quality of the adapted guidelines and to positively influence implementation.


Photochemical Synthesis of 4-Oxobutanal Acetals and of 2-Hydroxycyclobutanone Ketals.
Irradiation of α,β-unsaturated ketones (aliphatic, both open chain and cyclic as well as aryl substituted) in 1,3-dioxolane in the presence of a sensitizer (benzophenone or anthraquinone) led to 4-oxobutanal acetals in fair to excellent yield through a very simple procedure (workup in most cases by bulb-to-bulb distillation). The resulting acetals were irradiated to give 2-hydroxycyclobutanone ketals, again through a simple procedure that gave a good yield with open-chain aliphatic derivatives.


[Ultrafine particle number concentration and size distribution of vehicle exhaust ultrafine particles].
Ultrafine particle (UFP) number concentrations obtained from three different vehicles were measured using fast mobility particle sizer (FMPS) and automobile exhaust gas analyzer. UFP number concentration and size distribution were studied at different idle driving speeds. The results showed that at a low idle speed of 800 rmin-1 , the emission particle number concentration was the lowest and showed a increasing trend with the increase of idle speed. The majority of exhaust particles were in Nuclear mode and Aitken mode. The peak sizes were dominated by 10 nm and 50 nm. Particle number concentration showed a significantly sharp increase during the vehicle acceleration process, and was then kept stable when the speed was stable. In the range of 0. 4 m axial distance from the end of the exhaust pipe, the particle number concentration decayed rapidly after dilution, but it was not obvious in the range of 0. 4-1 m. The number concentration was larger than the background concentration. Concentration of exhaust emissions such as CO, HC and NO showed a reducing trend with the increase of idle speed,which was in contrast to the emission trend of particle number concentration.


Unveiling the Fine Structural Distortion of Atomically Thin Bi2 O2 Se by Third-Harmonic Generation.
Bismuth oxyselenide (Bi2 O2 Se), a new type of 2D material, has recently attracted increased attention due to its robust bandgap, stability under ambient conditions, and ultrahigh electron mobility. In such complex oxides, fine structural distortion tends to play a decisive role in determining the unique physical properties, such as the ferrorotational order, ferroelectricity, and magnetoelasticity. Therefore, an in-depth investigation of the fine structural symmetry of Bi2 O2 Se is necessary to exploit its potential applications. However, conventional techniques are either time consuming or requiring tedious sample treatment. Herein, a noninvasive and high-throughput approach is reported for characterizing the fine structural distortion in 2D centrosymmetric Bi2 O2 Se by polarization-dependent third-harmonic generation (THG). Unprecedentedly, the divergence between the experimental results and the theoretical prediction of the perpendicular component of polarization-dependent THG indicates a fine structural distortion, namely, a <1.4° rotation of the oxygen square in the tetragonal (Bi2 O2 ) layers. This rotation breaks the intrinsic mirror symmetry of 2D Bi2 O2 Se, eventually reducing the symmetry from the D4h to the C4h point group. The results demonstrate that THG is highly sensitive to even fine symmetry variations, thereby showing its potential to uncover hidden phase transitions and interacting polarized sublattices in novel 2D material systems.


Pulmonary arteriovenous fistulas occluded by percutaneous introduction of coil springs.
Between July 1980 and July 1983, we occluded 30 pulmonary arteriovenous fistulas (PAVFs) in four patients by percutaneous placement of coil springs. All patients had significant right-to-left shunts and hypoxemia. One presented with recurrent cerebral abscesses following bilateral thoracotomy and lobectomy. The technique requires advancement of the catheter superselectively into the feeding artery just proximal to the fistula. Occlusion at this site preserves the maximum amount of functioning pulmonary parenchyma. Frequently more than one coil spring is required for occlusion. In our experience, the coil spring is a safe, effective, economical vaso-occlusive device for management of PAVFs.


Identification and characterization of phage-resistance genes in temperate lactococcal bacteriophages.
The sie2009 gene, which is situated between the genes encoding the repressor and integrase, on the lysogeny module of the temperate lactococcal bacteriophage Tuc2009, was shown to mediate a phage-resistance phenotype in Lactococcus lactis against a number of bacteriophages. The Sie2009 protein is associated with the cell membrane and its expression leaves phage adsorption, transfection and plasmid transformation unaffected, but interferes with plasmid transduction, as well as phage replication. These observations indicate that this resistance is as a result of DNA injection blocking, thus representing a novel superinfection exclusion system. A polymerase chain reaction (PCR)-based strategy was used to screen a number of lactococcal strains for the presence of other prophage-encoded phage-resistance systems. This screening resulted in the identification of two such systems, without homology to sie2009, which were shown to mediate a phage-resistance phenotype similar to that conferred by sie2009. To our knowledge, this is the first description of a phage-encoded super-infection exclusion/injection blocking mechanism in the genus Lactococcus.


The primitive endoderm lineage of the mouse blastocyst: sequential transcription factor activation and regulation of differentiation by Sox17.
Cells of the primitive endoderm (PrE) and the pluripotent epiblast (EPI), the two lineages specified within the inner cell mass (ICM) of the mouse blastocyst stage embryo, are segregated into adjacent tissue layers by the end of the preimplantation period. The PrE layer which emerges as a polarized epithelium adjacent to the blastocoel, with a basement membrane separating it from the EPI, has two derivatives, the visceral and parietal endoderm. In this study we have investigated the localization of two transcriptional regulators of the SOX family, SOX17 and SOX7, within the PrE and its derivatives. We noted that SOX17 was first detected in a salt-and-pepper distribution within the ICM, subsequently becoming restricted to the nascent PrE epithelium. This dynamic distribution of SOX17 resembled the localization of GATA6 and GATA4, two other PrE lineage-specific transcription factors. By contrast, SOX7 was only detected in PrE cells positioned in contact with the blastocoel, raising the possibility that these cells are molecularly distinct. Our observations support a model of sequential GATA6 > SOX17 > GATA4 > SOX7 transcription factor activation within the PrE lineage, perhaps correlating with the consecutive periods of cell lineage 'naïvete', commitment and sorting. Furthermore our data suggest that co-expression of SOX17 and SOX7 within sorted PrE cells could account for the absence of a detectable phenotype of Sox17 mutant blastocysts. However, analysis of implantation-delayed blastocysts, revealed a role for SOX17 in the maintenance of PrE epithelial integrity, with the absence of SOX17 leading to premature delamination and migration of parietal endoderm.


Extended intrathoracic resection for lung cancer. Follow-up of 49 cases.
Extended resection was performed for primary lung cancer (stage III) on 49 patients in 1973-1982. Their mean age was 61 (38-76) years. In addition to pneumonectomy (29) or lobectomy (20), surgery included resection of the thoracic wall (8 cases) left atrium (12), pericardium (15), parietal pleura (13) and oesophagus (1 case). Among the 47 "surgical survivors" (96%), the mean survival time was 19.9 +/- SD 20.3 months, and only four patients (9%) were alive after 5 years or more. The cumulative 5-year survival was 14% (4/29 patients). Poorly differentiated tumour forms (squamous cell cancer) carried the worst prognosis, whereas the type of resection and presence or absence of lymph-node metastases did not per se influence survival. The prognosis in extended resection is poorer than in standard lung resection, but superior to that in simple exploration. The surgeon therefore should always be prepared to extend a planned resection when a patient on the operating table is found to have extension of lung cancer to other intrathoracic organs, since only in invasion of the chest wall is the surgical strategy as a rule clear from the outset.


[Bactericidal activities of isepamicin and ofloxacin against Pseudomonas aeruginosa evaluated using an in vitro pharmacokinetic simulation system].
Bactericidal activities of isepamicin and ofloxacin against Pseudomonas aeruginosa E7 were examined using an in vitro computer programmed pharmacokinetic simulation system. Concentration of the drugs simulated the pharmacokinetic data obtained in healthy human adult subjects after 200 mg or 400 mg I.M. administration of isepamicin (ISP), and 300 mg P.O. administration of ofloxacin (OFLX). P. aeruginosa cell counts were depressed by ISP or OFLX to -4 log -(-)5 log levels of magnitude below the initial cell counts. The time required in recovery of cell counts to the initial level after treatment with ISP (200 mg) was longer than that after OFLX (300 mg) treatment. An excellent synergistic effect was observed between ISP and OFLX.


Breathing cessation events that compose the apnea-hypopnea index are distinctively associated with the adverse outcomes in Alzheimer's disease.
Previous studies challenge the impact of obstructive sleep apnea (OSA) once patients are diagnosed with Alzheimer's disease (AD). Nevertheless, OSA recognizably disrupts sleep, and relevant associations between sleep, AD pathological markers, and cognition have been demonstrated. We aimed to further explore this, evaluating the associations between each breathing cessation event that compose the apnea-hypopnea index (AHI) and the sleep structure to finally investigate whether this was related to increased levels of AD markers and higher cognitive decline. Observational, prospective study, including consecutive patients diagnosed with mild-moderate AD. The participants were submitted to overnight polysomnography followed by a cerebrospinal fluid collection for AD pathological markers levels determination. Neuropsychological assessment was performed at baseline and after 12 months of follow-up. The cohort was composed of 116 patients (55.2% females) with a median [p25;p75] age of 76.0 [72.0;80.0] years and an AHI of 25.9 [15.1;48.5], which was mainly defined by the presence of hypopneas and obstructive apneas. These were distinctively associated with the sleep structure, with obstructive apneas being related to arousals and sleep lightening and hypopneas being related to an increased number of arousals only. Despite having a lower frequency, mixed and central apneas also presented associations with the sleep structure, particularly increasing the time spent in the lighter sleep stages. In relation to AD pathological markers, obstructive and mixed apneas were related to an augment in neurofilament light levels while hypopneas were associated with a higher phosphorylated-tau/amyloid-beta protein ratio. Hypopneas were the most important event for an increased cognitive decline at the 12-month follow-up. Our findings highlight the importance of a patient-centered approach, with a comprehensive and detailed analysis of the AHI to effectively predict the different outcomes and tailor the appropriate therapeutic strategies.