The 3-cycle weighted spectral distribution in evolving community-based networks.
One of the main organizing principles in real-world networks is that of network communities, where sets of nodes organize into densely linked clusters. Many of these community-based networks evolve over time, that is, we need some size-independent metrics to capture the connection relationships embedded in these clusters. One of these metrics is the average clustering coefficient, which represents the triangle relationships between all nodes of networks. However, the vast majority of network communities is composed of low-degree nodes. Thus, we should further investigate other size-independent metrics to subtly measure the triangle relationships between low-degree nodes. In this paper, we study the 3-cycle weighted spectral distribution (WSD) defined as the weighted sum of the normalized Laplacian spectral distribution with a scaling factor n, where n is the network size (i.e., the node number). Using some diachronic community-based network models and real-world networks, we demonstrate that the ratio of the 3-cycle WSD to the network size is asymptotically independent of the network size and strictly represents the triangle relationships between low-degree nodes. Additionally, we find that the ratio is a good indicator of the average clustering coefficient in evolving community-based systems.


Enantiospecific Total Synthesis of (-)-Japonicol C.
An efficient and convergent first total syntheses of (±)-japonicol B and (-)-japonicol C have been completed. The notable points of the synthetic route are Lewis-acid-catalyzed Friedel-Crafts reaction for one pot C-C and C-O bond formations resulting in construction of the tricyclic meroterpenoid skeleton, one pot Pd(OH)2/C-catalyzed isomerization/hydrogenation, and site selective sp3 C-H oxidation.


Development of a pharmacy resident rotation to expand decentralized clinical pharmacy services.
The development of a pharmacy resident rotation to expand decentralized clinical pharmacy services is described. In an effort to align with the initiatives proposed within the ASHP Practice Advancement Initiative, the department of pharmacy at Cleveland Clinic, a 1,400-bed academic, tertiary acute care medical center in Cleveland, Ohio, established a goal to provide decentralized clinical pharmacy services for 100% of patient care units within the hospital. Patient care units that previously had no decentralized pharmacy services were evaluated to identify opportunities for expansion. Metrics analyzed included number of medication orders verified per hour, number of pharmacy dosing consultations, and number of patient discharge counseling sessions. A pilot study was conducted to assess the feasibility of this service and potential resident learning opportunities. A learning experience description was drafted, and feedback was solicited regarding the development of educational components utilized throughout the rotation. Pharmacists who were providing services to similar patient populations were identified to serve as preceptors. Staff pharmacists were deployed to previously uncovered patient care units, with pharmacy residents providing decentralized services on previously covered areas. A rotating preceptor schedule was developed based on geographic proximity and clinical expertise. An initial postimplementation assessment of this resident-driven service revealed that pharmacy residents provided a comparable level of pharmacy services to that of staff pharmacists. Feedback collected from nurses, physicians, and pharmacy staff also supported residents' ability to operate sufficiently in this role to optimize patient care. A learning experience developed for pharmacy residents in a large medical center enabled the expansion of decentralized clinical services without requiring additional pharmacist full-time equivalents.


Early thiopurine maintenance is associated with reduced proximal disease progression and colectomy rate in ulcerative colitis.
Thiopurines effectively maintain remission in ulcerative colitis patients. Whether early initiation of thiopurines after ulcerative colitis diagnosis decreases proximal disease progression and colectomy rates is not known. We conducted a cohort study of ulcerative colitis subjects recruited from 1970 to 2009. Early thiopurine maintenance was defined as commencement of azathioprine or mercaptopurine within 5 years of diagnosis and maintenance for at least 6 months. Propensity score matching was conducted to correct for confounders influencing early thiopurine introduction. Outcomes of interest were colectomy rate and endoscopic proximal disease extension. 982 consecutive ulcerative colitis subjects (12 879 patient-years) were recruited with 116 requiring colectomy. Thiopurines initiation and maintenance increased over time with median time to thiopurine commencement decreasing from 23 years in the first decade to 2 years in the last decade (P < 0.0001). Multivariate analysis showed that early thiopurine maintenance significantly decreased the need for colectomy [hazard ratio, 0.13; 95% confidence interval (CI):0.03-0.55; P = 0.006]. The number of subjects needed to be treated to reduce one colectomy at 5 and 10 years was 18 (95% CI, 16- 36) and 12 (95% CI, 11-25). After propensity score matching, early thiopurine maintenance was significantly associated with decreased colectomy (hazard ratio, 0.10; 95% CI, 0.03-0.43; P = 0.002) and proximal progression of disease extent (hazard ratio, 0.26; 95% CI, 0.10-0.78; P = 0.015). Early thiopurine maintenance for >6 months is significantly associated with reduced colectomy and proximal progression of disease extent in ulcerative colitis.


Milk fermentation with prebiotic flour of Vasconcellea quercifolia A.St.-Hil.
Non-conventional food plants have bioactive compounds and a high nutritional value. Among these, Vasconcellea quercifolia has nutritional benefits, but it is also easy to cultivate and has a low production cost. In this study, the flour from the unripe fruit of V. quercifolia was evaluated in terms of its potential as a prebiotic for the probiotic bacteria Lactobacillus acidophilus and Bifidobacterium lactis. To do so, fermented milk samples were prepared with 2%, 3%, and 6% of flour and 8.25 log CFU/mL of each microorganism. Samples were analyzed in terms of the number of viable cells of L. acidophilus and B. lactis, as well as pH level, total solids, titratable acidity, and texture in the course of 21 days of storage at 4ºC. The obtained microbial viability revealed the in vitro symbiotic effect of flour from V. quercifolia on the probiotic strains of L. acidophilus and B. lactis, which reached 10.20 and 11.19 log CFU/mL, respectively, after 21 days of storage, showing a significant difference in cell growth of 1.7 and 2.5 log CFU/mL compared with the control. The pH level decreased from 4.8 to 4.5 after storage time, so it did not alter the conditions for the growth of bacteria. The physical and chemical parameters analyzed did not reveal significant differences (p > 0.05), which indicates product stability. Therefore, flour from the unripe fruit of V. quercifolia has a prebiotic property and can be used as a nutritional supplement for L. acidophilus and B. lactis.


Obtaining of a rich-cellulose material from black wattle (Acacia mearnsii De Wild.) bark residues.
Black wattle (Acacia mearnsii De Wild.) barks are residues produced by tannin industries in huge quantities, which are normally discharged on environmental or used for energy production. Therefore, this study aimed to evaluate the use of black wattle bark residues as a raw material on obtaining of a rich-cellulose material by alkaline (MET1), acetosolv (MET2), and organosolv (MET3) procedures. The results obtained indicated that the alkaline methodology, followed by a bleaching step (MET1), promoted klason lignin and hemicellulose removals more efficiently. It was possible to observe that better results were achieved using NaOH concentration of 6% (wt%), at 65 °C for 2.5 h, presenting a yield of 63.24 ± 1.25%, and a reduction on klason lignin content of almost 90.45%. Regarding the bleaching step, it was possible to obtain a material free of non-cellulosic compounds with a yield of 78.28 ± 1.48%. Thermogravimetric analysis indicated the removal of lignin and hemicellulose as well as an increase in cellulose degradation temperature, due to changes in crystalline phases. According to X-ray diffraction (XRD), the procedures employed have led to an increase in crystallinity from 66.27 to 91.78% due to the removal of non-cellulosic compounds. Scanning electron microscopy (SEM) showed morphological alterations in accordance with the removal of non-cellulosic compounds.


The Prozac boom and its placebogenic counterpart -- a culturally fashioned phenomenon.
The placebo effect describes the mind-body process of altering the body's physiological state as well as the brain's neurological state. Catalyzed by the mind's believing in a certain drug, ritual, and/or treatment, it generally refers to the phenomenon of an ill individual recovering to health. Subsequent to the Prozac boom (fluoxetine), which occurred during the 1980s and 90s in the United States, a new form of placebogenic phenomena was defined: 'cosmetic psychopharmacology', whereby the healthy individual is transformed to fit better in his/her cultural medium (defined by one's values and beliefs). In order to discover how cultural metaphors (e.g. media-generated symbolism, social ideals) influence psychopharmacological treatment, this report investigates the following questions: Is the Prozac Boom culturally fashioned? Is cosmetic psychopharmacology culturally fashioned? Are cosmetic psychopharmacology and its ability to better the individual (relative to American ideals) a placebogenic phenomenon? The data and speculation for the present report was obtained via a cultural and critical review. It would appear that (1) the Prozac Boom and subsequently its by product, cosmetic psychopharmacology, are culturally fashioned; (2) cosmetic psychopharmacology is considered to result from one's belief in a drug and thus is placebo-influenced. Media-generated symbolism, which represents and reciprocally fashions the ideals and values of that society, influence the social perceptions of a drug's effectiveness and the quality of a particular treatment. In the clinical setting, the influential role of these preconceived notions about a certain treatment and/or drug need to be further considered and studied.


History of mental health services in South Africa. Part VIII. Services for epileptics.
The development of services for epileptics in South Africa is reviewed. In the field of education, the history of the Jan Kriel school at Kuils River in the Western Cape is described. Treatment is provided at government mental hospitals, institutions for defectives, and general hospitals. The Epileptic Employment Association provides epileptics with work and opportunity to live a normal life. Information about epilepsy is provided by the South African National Epilepsy League, which also provides opportunities for employment.


Prospective trial of daily and extended wear disposable contact lenses.
The current study prospectively evaluates the response to daily and extended wear of disposable lenses with each patient acting as his/her own control. This paradigm allowed for elimination of individual variation as a confounding factor, as well as determining whether an intrinsic factor, other than lens wear, predisposed patients to complications. One hundred thirty-four patients were randomly assigned to contralateral daily wear (DW) or extended wear (EW) with Acuvue lenses for 1 year. All lenses were disposed of on a weekly basis. Bilateral bacteriology of lids, conjunctivae, lenses, and fingers was carried out on those patients presenting with complications. The results after 1 year indicate a higher incidence of complications in the EW eye (peripheral infiltrative keratopathy, 12%; corneal striae, 3%). No significant clinical complications occurred in the DW eye. Microbiological cultures did not reveal any significant difference between those eyes with keratopathy and those of controls. The most common pathogen was Staphyloccocus epidermidis. No gram-negative organisms grew from any of the culture sites. The results of this study indicate that extended wearing schedules, and not the lens entity, predispose the patient to a higher risk of keratopathy with disposable contact lenses. No microbiological association with the adverse events could be determined, and no intrinsic patient factor could be demonstrated that would predict the likelihood of complications.


Arbuscular mycorrhizal fungi in chronically petroleum-contaminated soils in Mexico and the effects of petroleum hydrocarbons on spore germination.
Arbuscular mycorrhizal fungi (AMF) have been hypothesized to enhance plant adaptation and growth in petroleum-contaminated soils. Nevertheless, neither AMF-biodiversity under chronically petroleum-contaminated soils nor spore germination response to petroleum hydrocarbons has been well studied. Chronically petroleum-contaminated rhizosphere soil and roots from Echinochloa polystachya, Citrus aurantifolia and C. aurantium were collected from Activo Cinco Presidentes, Tabasco, Mexico. Root colonization and spore abundance were evaluated. Additionally, rhizosphere soil samples were propagated using Sorghum vulgare L. as a plant trap under greenhouse conditions; subsequently, AMF-spores were identified. AMF-colonization ranged from 63 to 77% while spore number ranged from 715 to 912 in 100 g soil, suggesting that AMF tolerate the presence of petroleum hydrocarbons in the rhizosphere. From grass species, four AMF-morphospecies were identified: Glomus ambisporum, G. sinuosum (previously described as Sclerocystis sinuosum), Acaulospora laevis, and Ambispora gerdermanni. From citrus trees, four AMF-species were also identified: Scutellospora heterogama, G. ambisporum, Acaulospora scrobiculata, and G. citricola. In a second study, it was observed that spore germination and hyphal length of G. mosseae, G. ambisporum, and S. heterogama were significantly reduced by either volatile compounds of crude oil or increased concentrations of benzo[a ]pyrene or phenanthrene in water-agar.


Transvaginal appendectomy in morbidly obese patient.
Introduction. Laparoscopic appendectomy has significant benefits in obese patients. However, morbid obesity can be accepted as an exclusion criterion for natural orifice transluminal endoscopic surgery (NOTES). Here, we present a transvaginal appendectomy in a 66-year-old morbidly obese (BMI 36 kg/m(2), ASA III) patient. Case and Technique. Acute appendicitis was suspected based on history, physical examination, laboratory tests, and ultrasound findings. During laparoscopic surgery, a 5 mm trocar was inserted through the umbilicus and a 5 mm telescope was placed. A 12 mm trocar and a 5 mm grasper were inserted separately through the posterior fornix of the vagina under laparoscopic guidance. The appendix was divided with an endoscopic stapler through the transvaginal 12 mm trocar and removed from the same trocar. The operating time was 75 minutes with minimal blood loss (<10 mL). The patient was discharged 16 hours after surgery uneventfully and she did not require any analgesic administration. Conclusion. To the best of our knowledge, this is the first clinical case that focuses on the transvaginal appendectomy at morbid obesity. We can say that morbid obesity does not constitute an obstacle for treatment of acute appendicitis by transvaginal endoscopic surgery.


The DEPARTS Score: A Novel Tool for Predicting Discharge Disposition in Geriatric Trauma Patients.
Geriatric trauma patients (GTPs) represent a high-risk population for needing post-acute care, such as skilled nursing facilities (SNFs) and long-term acute care hospitals (LTACs), due to a combination of traumatic injuries and baseline functional health. As there is currently no well-established tool for predicting these needs, we aimed to create a scoring tool that predicts disposition to SNFs/LTACs in GTPs. The adult 2017 Trauma Quality Improvement Program database was divided at random into two equal sized sets (derivation and validation sets) of GTPs >65 years old. First, multiple logistic regression models were created to determine risk factors for discharge to a SNF/LTAC in admitted GTPs. Second, the weighted average and relative impact of each independent predictor was used to derive a DEPARTS (Discharge of Elderly Patients After Recent Trauma to SNF/LTAC) score. We then validated the score using the area under the receiver-operating curve (AROC). Of 66 479 patients in the derivation set, 36 944 (55.6%) were discharged to a SNF/LTAC. Number of comorbidities, fall mechanism, spinal cord injury, long bone fracture, and major surgery were each independent predictors for discharge to SNF/LTAC, and a DEPARTS score was derived with scores ranging from 0 to 19. The AROC for this was .74. In the validation set, 66 477 patients also had a SNF/LTAC discharge rate of 55.7%, and the AROC was .74. The DEPARTS score is a good predictor of SNF/LTAC discharge for GTPs. Future prospective studies are warranted to validate its accuracy and clinical utility in preventing delays in discharge.


Linking ATR-FTIR and Raman features to phenolic extractability and other attributes in grape skin.
The importance of wine phenolics on the sensory characteristic of red wines is well-known. Therefore, it is necessary to control the extractability of phenolic compounds from grape skins, which depends significantly on grape ripeness and hence, on cell wall degradation. In the present study, attenuated total reflectance Fourier transform infrared (ATR-FTIR) and Raman spectra of grape skin have been recorded. Then, these spectral matrices have been studied and the main spectral features have been linked to extractabilities of phenolic compounds (anthocyanins, flavanols and total phenols). Moreover, spectral differences between external and internal grape skin surfaces also have been studied. It has been confirmed that the amount of polysaccharides and the degree of esterification of pectins have significant influence on the phenolic extractability levels of grape skin tissue.


Spatio-temporal coherence of free electron laser pulses in the soft x-ray regime.
The temporal coherence properties of soft x-ray free electron laser pulses at FLASH are measured at 23.9 nm by interfering two time-delayed partial beams directly on a CCD camera. The partial beams are obtained by wave front beam splitting in an autocorrelator operating at photon energies from h nu = 30 to 200 eV. At zero delay a visibility of (0.63+/- 0.04) is measured. The delay of one partial beam reveals a coherence time of 6 fs at 23.9 nm. The visibility further displays a non-monotonic decay, which can be rationalized by the presence of multiple pulse structure.


Glucose metabolism in cardiovascular surgery.
During the past few years, it has become evident that metabolic control is a major determinant of postoperative outcomes, not only for diabetic patients but for all patients undergoing surgery.In cardiac and vascular surgery, myocardial ischemia is a common challenge and the management of hyperglycemia should be part of the strategy aimed at optimizing cardiac protection during these types of surgery, since performed in high risk patients. Little informations are available on the relation between glucose substrate and the type of anesthesia and few studies have been performed on glucose metabolism in the perioperative risk assessment as well as on intraoperative and post surgical management of hyperglycemia in patients submitted to cardiac and vascular surgery. Evidence exists that even slight increased in glycemia are detrimental for patients (diabetic and non) elective for cardiac and vascular surgery, though the precise details of the timing of insulin therapy, the desired target serum glucose level, and the duration of therapy are so far to be completely elucidated. Anesthestiologists can therefore affect outcome by simply preserving a normal blood glucose concentration initiating in the operating room. The challenge to optimize glucose control should begin during preoperative evaluation.


Tumor-cell-induced platelet aggregation is a glycoprotein-dependent and lipoxygenase-associated process.
To characterize the platelet receptor sites and the platelet metabolic pathways involved in tumor-cell-induced platelet aggregation, we have used a homologous system consisting of human platelets and 2 tumor cell lines of human origin, which activate platelets through different mechanisms. Preincubation of platelets with an MAb against platelet glycoprotein Ib partially blocked tumor-cell-induced platelet aggregation, and preincubation of platelets with an MAb against the glycoprotein complex GPIIb/IIIa totally blocked the aggregation induced by the 2 tumor-cell lines. No inhibitory effect was found when platelets were treated with PAF-receptor antagonists or with specific peptides which block the platelet sites involved in bacterially induced platelet aggregation. Compounds which raised intra-platelet cAMP levels inhibited tumor-cell-induced platelet aggregation in a dose-related manner. Inhibition of cyclo-oxygenase by aspirin which blocked TxB2 formation by platelets did not inhibit platelet aggregation induced by tumor cells whereas the BW755 compound which inhibits cyclo- and lipoxygenase blocked platelet aggregation. These results demonstrate that tumor-cell-induced platelet aggregation is a glycoprotein-dependent and a lipoxygenase-associated phenomenon.


Caryophyllene Sesquiterpenes from Pulicaria vulgaris Gaertn.: Isolation, Structure Determination, Bioactivity and Structure-Activity Relationship.
A new caryophyllene, named pulicaryenne A (1), along with four other known caryophyllene derivatives (2, 3, 4 and 5) were isolated from the ethyl acetate extract of aerial parts of Pulicaria vulgaris Gaertn. (Asteraceae). All compounds were isolated for the first time from this species. Compound 2 was identified as a new epimer of a known caryophyllene derivative isolated previously from P. dysenterica. Their structures were established by spectroscopic means including NMR analysis (1D- and 2D-NMR) and ESI-TOF-MS. All compounds were evaluated for their anticholinesterase, antityrosinase and cytotoxic activities against two human cell lines (A549 and HeLa). Results showed that compound 5 exhibited the highest cytotoxic effect against A549 and anticholinesterase activity with IC50 values of 8.50±0.75 and 6.45±0.09 μg/mL, respectively. Furthermore, compound 5 showed also an interesting antityrosinase activity with percent inhibition value of 79.0±2.5 % at 50 μg/mL. The bioactivity and drug likeness scores of the isolated compounds 1-5 were calculated using Molinspiration software and discussed. These results may suggest that the five caryophyllene derivatives endowed with good biological properties, which could be used as bioactive alternatives in pharmaceutical preparations.


The beneficial effect of statins treatment by stroke subtype.
Statins have shown some protective effect after ischaemic stroke in observational studies. However, this effect has never been assessed by etiological subtypes. Observational study using data from the Stroke Unit Data Bank from consecutive patients with cerebral infarction. Variables analyzed: demographic data, cardiovascular risk factors, treatment with statins at stroke onset, stroke severity, stroke subtype, in-hospital complications, length of stay, and functional status at discharge (modified Rankin Scale). A total of 2742 patients were included, 1539 were men. Mean age was 69.17 years (SD 12.19). Of these, 281 patients (10.2%) were receiving statins when admitted. The logistic regression analyses showed that previous treatment with statins was an independent predictor for better outcome at discharge among all strokes (OR, 2.08; 95% CI, 1.39 to 3.1) as well as for the atherothrombotic (OR, 2.79; 95% CI, 1.33 to 5.84) and lacunar strokes (OR, 2.28; 95% CI, 1.15 to 4.52) after adjustment for demographic data, risk factors, previous treatments, stroke subtypes, stroke severity, in-hospital complications and length of stay. This benefit was not observed either in cardioembolic or in other etiology strokes. Previous treatment with statins is an independent factor associated with good outcomes in patients with ischaemic stroke. Atherothrombotic and small vessel strokes show the greatest benefit.


Effect of Adequate Thyroid Hormone Replacement on the Hypothalamo-Pituitary-Gonadal Axis in Premenopausal Women with Primary Hypothyroidism.
While the effects of thyroxine (T4) replacement on improving gonadal function in hypothyroid men has been well documented, the same has not been adequately studied in hypothyroid premenopausal women. Premenopausal women with overt hypothyroidism (thyroid-stimulating hormone [TSH] > 15 IU/L) were tested in the early follicular phase of their natural menstrual cycles or after a progesterone challenge for gonadotropins, estradiol (E2), and prolactin (PRL). They were then treated adequately with T4 replacement and retested under similar circumstances for the same parameters ≥2 months after the restoration of euthyroidism. Forty premenopausal hypothyroid women were evaluated at baseline and ≥2 months after adequate T4 replacement. At baseline, there was an inverse correlation of the gonadotropins (luteinizing hormone [LH] and follicle-stimulating hormone [FSH]) and TSH, prolactin (PRL) and free T4 (fT4), and E2 and PRL. After normalization of the thyroid function, there was a significant fall in PRL (p < 0.001) accompanied by a rise in serum E2 (p < 0.001). There were no changes in the levels of the gonadotropins LH and FSH. The proportion of patients with hyperprolactinemia fell 5-fold, from 5/40 to 1/40. While there were 5 patients with low estrogen prior to treatment, there were none with hypoestrogenemia after treatment. Hypothyroidism is associated with a reversible partial suppression of the hypothalamo-pituitary-gonadal axis in premenopausal women, demonstrated by lower E2 along with a mild elevation of PRL. Treatment of hypothyroidism improves the level of estrogen and lowers the level of PRL.


People with chronic low back pain have poorer balance than controls in challenging tasks.
To compare the balance of individuals with and without chronic low back pain during five tasks. The participants were 20 volunteers, 10 with and 10 without nonspecific chronic low back pain, mean age 34 years, 50% females. The participants completed the following balance tasks on a force platform in random order: (1) two-legged stance with eyes open, (2) two-legged stance with eyes closed, (3) semi-tandem with eyes open, (4) semi-tandem with eyes closed and (5) one-legged stance with eyes open. The participants completed three 60-s trials of tasks 1-4, and three 30-s trials of task 5 with 30-s rests between trials. The center of pressure area, velocity and frequency in the antero-posterior and medio-lateral directions were computed during each task, and compared between groups and tasks. Participants with chronic low back pain presented significantly larger center of pressure area and higher velocity than the healthy controls (p < 0.001). There were significant differences among tasks for all center of pressure variables (p < 0.001). Semi-tandem (tasks 3 and 4) and one-leg stance (task 5) were more sensitive to identify balance impairments in the chronic low back pain group than two-legged stance tasks 1 and 2 (effect size >1.37 vs. effect size <0.64). There were no significant interactions between groups and tasks. Individuals with chronic low back pain presented poorer postural control using center of pressure measurements than the healthy controls, mainly during more challenging balance tasks such as semi-tandem and one-legged stance conditions. Implications for Rehabilitation People with chronic low back had poorer balance than those without it. Balance tasks need to be sensitive to capture impairments. Balance assessments during semi-tandem and one-legged stance were the most sensitive tasks to determine postural control deficit in people with chronic low back. Balance assessment should be included during rehabilitation programs for individuals with chronic low back pain for better clinical decision making related to balance re-training as necessary.


[Repair of the mammalian central nervous system: the "spinal cord" model].
The central nervous system of adult mammals has been classically considered as structurally rigid, tightly wired, and unable to be repaired. We have shown that there exists a rather considerable degree of intrinsic plasticity due to the neurons themselves, but merely to glial cells and to multipotent stem cells. The spinal cord constitutes a good model on which we could demonstrate, with vascular and traumatic animal paradigms, that an early pharmacologic intervention could reduce significantly the extent of lesions and the subsequent functional deficit. Moreover, we showed that regeneration of severed central axons could occur, provided that the astrocytes' component of the glial scar was modified. Finally, transplants of embryonic neurons were shown to repair the axonal circuitry below a sectioned cord, and to restore reflex functions. All these data point to unprecedented perspectives of efficient therapies in acute and chronic neurological diseases.


Evidence for multiple colonisations and Wolbachia infections shaping the genetic structure of the widespread butterfly Polyommatus icarus in the British Isles.
The paradigm of isolation in southern refugia during glacial periods followed by expansions during interglacials, producing limited genetic differentiation in northern areas, dominates European phylogeography. However, the existence of complex structured populations in formerly glaciated areas, and islands connected to mainland areas during glacial maxima, call for alternative explanations. We reconstructed the mtDNA phylogeography of the widespread Polyommatus Icarus butterfly with an emphasis on the formerly glaciated and connected British Isles. We found distinct geographical structuring of CO1 haplogroups, with an ancient lineage restricted to the marginal European areas, including Northern Scotland and Outer Hebrides. Population genomic analyses, using ddRADSeq genomic markers, also reveal substantial genetic structuring within Britain. However, there is negligble mito-nuclear concordance consistent with independent demographic histories of mitochondrial versus nuclear DNA. While mtDNA-Wolbachia associations in northern Britain could account for the geographic structuring of mtDNA across most of the British Isles, for nuclear DNA markers (derived from ddRADseq data) butterflies from France cluster between northern and southern British populations - an observation consistent with a scenario of multiple recolonisation. Taken together our results suggest that contemporary mtDNA structuring in the British Isles (and potentially elsewhere in Europe) largely results from Wolbachia infections, however, nuclear genomic structuring suggests a history of at least two distinct colonisations. This two-stage colonisation scenario has previously been put forth to explain genetic diversity and structuring in other British flora and fauna. Additionally, we also present preliminary evidence for potential Wolbachia-induced feminization in the Outer Hebrides.


Multiple sclerosis: serum gamma globulin and demyelination in organ culture.
Multiple sclerosis (MS) sera frequently demyelinate organotypic central nervous system (CNS) tissue cultures. To elucidate the possible role of gamma globulins in this form of experimental demyelination we depleted MS sera of all gamma globulins by immunoabsorption and then compared their demyelinating activity with that of the unabsorbed sera. In only 2 out of 16 patients was some demyelinating activity detected in the gamma globulin fraction. In all patients, most of the demyelinating activity was not associated with gamma globulins. In gel filtration experiments, this non-gamma globulin activity was detected in a high-molecular-weight and in a low-molecular-weight fraction.


Genistein enhances antigen-specific cytokine production in female DO11.10 transgenic mice.
Genistein is a phytoestrogen contained at high levels in soy products and has been shown to regulate immunoresponse. In this study, we evaluated the effects of genistein on the production of cytokines from antigen (Ag)-specific T cells using DO11.10 transgenic mice because the direct effect of genistein on Ag-specific cytokine production has not been elucidated. The oral administration of 20 mg/kg genistein increased IFN-gamma and IL-4 production from DO11.10+ T cells in response to ovalbumin (OVA)323-339 peptide in female DO11.10 mice. Analysis of intracellular cytokine synthesis revealed that the percentages of cytokine-producing cells in the control and genistein-treated groups were not different, indicating that increased cytokine production occurred at the single-cell level. In contrast to the female mice, genistein did not increase cytokine production in male mice, suggesting that the effect of genistein on cytokine production is gender-dependent.


Zolpidem arouses patients in vegetative state after brain injury: quantitative evaluation and indications.
To investigate the efficacy and indications of zolpidem, a nonbenzodiazepine hypnotic, inducing arousal in vegetative state patients after brain injury. One hundred sixty-five patients were divided into 4 groups, according to area of brain damage and injury mechanism. All patients' brains were imaged by Tc-ECD single-photon emission computerized tomography (SPECT), before and 1 hour after treatment with 10 mg of zolpidem. Simultaneously, 3 quantitative indicators of brain function and damage were obtained using cerebral state monitor. Thirty-eight patients withdrew from the study after the first zolpidem dose. The remaining 127 patients received a daily dose of 10 mg of zolpidem for 1 week and were monitored again at the end of this week. One hour after treatment with zolpidem, cerebral state index was increased and burst suppression reduced in both brain contrecoup contusion and space-occupying brain compression groups (P < 0.05). SPECT showed, 1 hour after medication, that cerebral perfusion was improved in both brain contrecoup contusion and space-occupying brain compression groups, but no changes were seen in primary and secondary brain stem injury groups. In the 127 patients' group, after 1 week of zolpidem treatment, all parameters obtained from cerebral state monitor were not statistically different compared with those after the initial medication (P > 0.05). Zolpidem is an effective medicine to restore brain function in patients in vegetative state after brain injury, especially for those whose brain injuries are mainly in non-brain-stem areas. Improvement of brain function is sudden rather than gradual.


Pro-inflammatory and pathogenic properties of Annexin-A1: the whole is greater than the sum of its parts.
According to Aristotle, "The whole is greater than the sum of its parts" and yet, although a long time has passed still, we seem to struggle to accept this universal concept. Searching in the literature for the biological function of Annexin-A1, one would find a wealth of information on its homeostatic and protective anti-inflammatory effects. However, very little has been said on its emerging role in a wide variety of pathological conditions ranging from cancer to autoimmunity. In this commentary, we will focus our attention on this novel pro-inflammatory and pathogenic "dark side" of Annexin-A1. We will summarize our current understanding of the signaling pathways regulated by this protein and link it to clinical and experimental evidences. Finally we will discuss assets and limitations of Annexin-A1 therapeutic strategies. Most importantly, we hope that this commentary will provide scientific support to "controversial" findings one might encounter while studying this fascinating protein.


Development and validation of a fast SFC method for the analysis of flavonoids in plant extracts.
Flavonoids from plants always show a wide range of biological activities. In the present study, a rapid and highly efficient supercritical fluid chromatography (SFC) method was developed for the separation of 12 flavonoids. After careful optimization, the 12 flavonoids were baseline separated on a ZORBAX RX-SIL column using gradient elution. A 0.1% phosphoric acid solution in methanol was found to be the most suitable polar mobile phase component for the separation of flavonoids. From the viewpoint of retention and resolution, a backpressure of 200bar and a temperature of 40°C were shown to give the best results. Compared with a previously developed reverse phase liquid chromatography method, the SFC method could provide flavonoid separations that were about three times faster, while maintaining good peak shape and comparable peak efficiency. This SFC method was validated and applied to the analysis of five flavonoids (kaempferol, luteolin, quercetin, luteoloside, buddleoside) present in Chrysanthemum morifolium Ramat. from different cultivars (Chuju, Gongju, Hangju, Boju). The results indicated a good repeatability and sensitivity for the quantification of the five analytes with RSDs for overall precision lower than 3%. The limits of detection ranged from 0.73 to 2.34μg/mL, while the limits of quantification were between 2.19 and 5.86μg/mL. The method showed that SFC could be employed as a useful tool for the quality assessment of Traditional Chinese medicines (TCMs) containing flavonoids as active components.


An Experimental and Master Equation Study of the Kinetics of OH/OD + SO2: The Limiting High-Pressure Rate Coefficients.
The kinetics of the reaction OH/OD + SO2 were studied using a laser flash photolysis/laser-induced fluorescence technique. Evidence for two-photon photolysis of SO2 at 248 nm is presented and quantified, and which appears to have been evident to some extent in most previous photolysis studies, potentially leading to values for the rate coefficient k1 that are too large. The kinetics of the reaction OH(v = 0) + SO2 (T = 295 K, p = 25-300 torr) were measured under conditions where SO2 photolysis was taken into account. These results, together with literature data, were modeled using a master equation analysis. This analysis highlighted problems with the literature data: the rate coefficients derived from flash photolysis data were generally too high and from the flow tube data too low. Our best estimate of the high-pressure limiting rate coefficient k1∞ was obtained from selected data and gives a value of (7.8 ± 2.2) × 10-13 cm3 molecule-1 s-1, which is lower than that recommended in the literature. A parametrized form of k1([N2],T) is provided. The OD(v = 0) + SO2 (T = 295 K, p = 25-300 torr) data are reported for the first time, and master equation analysis reinforces our assignment of k1∞.


Temperature relationships in Mycobacterium kansasii: correlation between heat inactivation of protein synthesis and thermal death.
The temperature relationships of Mycobacterium kansasii were investigated. The optimal temperature of growth of these bacteria was between 37 and 38 degrees C, and their thermal death point was about 70 degrees. The temperature characteristic of growth of M. kansasii was about 23,400 cal.mole-1. Experiments on the effect of temperature on protein synthesis showed that the temperature and time relationships required to complete and irreversibly inactivate protein synthesis correlated with thermal death. Judged from the data obtained, it was hypothesized that the initial cause of thermal death in the bacteria might be the heat inactivation of the protein synthetic machinery of the cells.


Flt-3 ligand synergizes with granulocyte colony-stimulating factor to increase neutrophil numbers and to mobilize peripheral blood stem cells with long-term repopulating potential.
Flt-3 ligand (FL) shares many features with stem cell factor (SCF), a widely documented cofactor for peripheral blood progenitor cell (PBPC) mobilization. We investigated the mobilization of PBPCs by FL in combination with granulocyte colony-stimulating factor (G-CSF). As a single agent, FL was a relatively modest mobilizer of PBPCs, resulting in 360 granulocyte/macrophage colony-forming cells (GM-CFCs)/mL blood (control, 155 GM-CFCs/mL blood) and no advantage in leukocyte recovery when these PBPCs were transplanted to irradiated recipient mice. G-CSF, on the other hand, mobilized over 20,000 GM-CFCs/mL blood, and the combination of G-CSF + FL resulted in over 100,000 GM-CFCs/mL blood. The combination of G-CSF + FL stimulated increased levels of monocytes and basophils in the peripheral blood. The performance of the mobilized PBPC product in irradiated hosts correlated with progenitor numbers resulting in long-term engraftment in association with accelerated short-term recovery of both leukocytes and platelets. These data demonstrate the potential of FL to synergize with G-CSF to mobilize PBPCs with both short- and long-term engraftment potential. The effect is similar to the synergistic interaction of G-CSF and SCF on PBPC mobilization. The use of FL as opposed to SCF may elicit a different spectrum of toxicities including lymphoid proliferation effects, in contrast to the mast cell degranulation effects of SCF. Clinical studies of FL are needed to evaluate its usefulness in man.


HF-free synthesis of anatase TiO2 nanosheets with largely exposed and clean {001} facets and their enhanced rate performance as anodes of lithium-ion battery.
An interface between toluene and water was utilized to synthesize ca. 10 nm thick of anatase TiO2 nanosheets (NSs) with 82% exposure of {001} facets. In this procedure, highly corrosive and toxic HF, which was generally used to prepare TiO2 NSs with largely exposed high energy facets, was avoided. Furthermore, the surfaces of the NSs were quite clean as suggested by XPS analysis. Serving as anode materials in lithium-ion batteries, these as-prepared anatase TiO2 NSs manifested a low initial irreversible capacity loss (12.5% at 1 C), an excellent capacity retention at 10 C charge-discharge rate (101.9 mA h g(-1) after 100 cycles), and enhanced rate performance at 0.5-10 C current rates in compared with Degussa P25 TiO2 nanoparticles (NPs). Their excellent electrochemical performances were mainly derived from the large proportion of {001} exposed facets and a very short diffusion pathway, which allowed fast and efficient Li(+) transportation in the electrodes.


Ischemic preconditioning in the intact rat heart is mediated by delta1- but not mu- or kappa-opioid receptors.
Our laboratory has previously shown that delta-opioid receptors are involved in the cardioprotective effect of ischemic preconditioning in the rat heart. However, this class of receptors consists of two subtypes, delta1, and delta2, and mu- or kappa-opioid receptors may also exist in the heart. Therefore, the purpose of the present study was to test the hypothesis that ischemic preconditioning is mediated through stimulation of one or both delta-opioid receptor subtypes. Anesthetized, open chest, male Wistar rats were assigned to 1 of 14 groups. All animals were subjected to 30 minutes of occlusion and 2 hours of reperfusion. Ischemic preconditioning was elicited by three 5-minute occlusion periods interspersed with 5 minutes of reperfusion. Two doses of 7-benzylidenenaltrexone (BNTX; 1 and 3 mg/kg i.v.), a selective delta1-opioid receptor antagonist, or naltriben (NTB; 1 and 3 mg/kg i.v.), a selective delta2-opioid receptor antagonist, were given before ischemic preconditioning. To test for a role of mu-opioid receptors, rats were pretreated with beta-funaltrexamine (beta-FNA; 15 mg/kg s.c), an irreversible mu-opioid receptor antagonist, 24 hours before ischemic preconditioning or given the mu-opioid receptor agonist D-Ala,2N-Me-Phe,4glycerol5-enkephalin (DAMGO) as three 5-minute infusions (1, 10, and 100 microg/kg per infusion i.v., respectively) interspersed with 5-minute drug-free periods before the prolonged ischemic and reperfusion periods (lowDAMGO, medDAMGO, and hiDAMGO, respectively). The involvement of kappa-opioid receptors was tested by administering one of two doses of nor-binaltorphimine (nor-BNI; 1 and 5 mg/kg i.v.) before ischemic preconditioning. Infarct size (IS) as a percent of the area at risk (AAR) was measured by triphenyltetrazolium stain. Ischemic preconditioning markedly reduced IS/AAR (14+/-4%, P<.05) compared with control (55+/-4%). NTB, beta-FNA, and nor-BNI were unable to block the cardioprotective effect of ischemic preconditioning. In addition, DAMGO had no effect on IS/AAR. However, the high dose of BNTX (3 mg/kg i.v.) significantly attenuated the cardioprotective effect of ischemic preconditioning (39+/-5%; P<.05 versus control and ischemic preconditioning). These results indicate that delta1-opioid receptors play an important role in the cardioprotective effect of ischemic preconditioning in the rat heart.


A series of 17 cases of congenital cystic adenomatoid malformation of the lung: management and outcome.
During a 5-year-period, 17 cases of congenital adenomatoid malformation of the lung were observed in the Department of Pediatric Surgery of Bologna University-S. Orsola-Malpighi Hospital; 16 cases were diagnosed in utero by ultra-sound. 13 patients had prenatal diagnosis between 21 and 23 weeks of gestation; 2 cases were diagnosed at 25 weeks and another one at 26 weeks. The other case came from another hospital, and the diagnosis was accidentally detected postnatally. In 3 cases the parents decided to terminate the pregnancy 3 cases had spontaneous improvement during the last weeks of gestation, and were perfectly normal at birth. One case was lost to follow-up; all remaining patients underwent resection. Among these patients only one was a nonsurvivor, while 9 have completely recovered. However, one patient developed persistent pulmonary hypertension, which could successfully be treated with drugs, another underwent laser treatment for laryngeal stenosis due to intubation. A special epidemiological information: 13 out 17 cases (76.5%) were female.


Spontaneous Facial Mimicry is Modulated by Joint Attention and Autistic Traits.
Joint attention (JA) and spontaneous facial mimicry (SFM) are fundamental processes in social interactions, and they are closely related to empathic abilities. When tested independently, both of these processes have been usually observed to be atypical in individuals with autism spectrum conditions (ASC). However, it is not known how these processes interact with each other in relation to autistic traits. This study addresses this question by testing the impact of JA on SFM of happy faces using a truly interactive paradigm. Sixty-two neurotypical participants engaged in gaze-based social interaction with an anthropomorphic, gaze-contingent virtual agent. The agent either established JA by initiating eye contact or looked away, before looking at an object and expressing happiness or disgust. Eye tracking was used to make the agent's gaze behavior and facial actions contingent to the participants' gaze. SFM of happy expressions was measured by Electromyography (EMG) recording over the Zygomaticus Major muscle. Results showed that JA augments SFM in individuals with low compared with high autistic traits. These findings are in line with reports of reduced impact of JA on action imitation in individuals with ASC. Moreover, they suggest that investigating atypical interactions between empathic processes, instead of testing these processes individually, might be crucial to understanding the nature of social deficits in autism. Autism Res 2016, 9: 781-789. © 2015 The Authors Autism Research published by Wiley Periodicals, Inc. on behalf of International Society for Autism Research.


Localization of the membrane interaction sites of Pal-like protein, HI0381 of Haemophilus influenzae.
HI0381 of Haemophilus influenzae was investigated by circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy. HI0381 is a 153-residue peptidoglycan-associated outer membrane lipoprotein, and a part of the larger Tol/Pal network. Here, we report its backbone (1)H, (15)N, and (13)C resonance assignments, and secondary structure predictions. About 97% of all of the (1)HN, (15)N, (13)CO, (13)C alpha, and (13)C beta resonances covering 131 non-proline residues of the 134 residue, mature protein, were clarified by sequential and specific assignments. CSI and TALOS analyses revealed that HI0381 contains five alpha-helices and five beta-strands. To characterize the structure of HI0381, the effects of pH and salt concentration were investigated by CD. In addition, the structural changes occurring when HI0381 was in a membranous environment were investigated by comparing its HSQC spectra and CD data in buffer and in DPC micelles; the results showed that helix alpha 4 and strand beta 4 became aligned with the membrane. We conclude that the conformation of HI0381 is affected by the membrane environment, implying that its folded state is directly related to its function.


Atypical Complications of Graves' Disease: A Case Report and Literature Review.
Graves' disease (GD) may display uncommon manifestations. We report a patient with rare complications of GD and present a comprehensive literature review. A 35-year-old woman presented with a two-week history of dyspnea, palpitations, and edema. She had a raised jugular venous pressure, goiter, and exophthalmos. Laboratory tests showed pancytopenia, a raised alkaline phosphatase level, hyperbilirubinemia (mainly direct bilirubin), and hyperthyroidism [TSH: <0.01 mIU/L (reference values: 0.45-4.5), fT4: 54.69 pmol/L (reference values: 9.0-20.0), and fT3: >46.08 pmol/L (reference values: 2.6-5.7)]. Her thyroid uptake scan indicated GD. Echocardiography showed a high right ventricular systolic pressure: 60.16 mmHg. Lugol's iodine, propranolol, cholestyramine, and dexamethasone were initiated. Hematologic investigations uncovered no reason for the pancytopenia; therefore, carbimazole was started. Workup for hepatic impairment and pulmonary hypertension (PH) was negative. The patient became euthyroid after 3 months. Leukocyte and platelet counts and bilirubin levels normalized, and her hemoglobin and alkaline phosphatase levels and right ventricular systolic pressure (52.64 mmHg) improved. This is the first reported single case of GD with the following three rare manifestations: pancytopenia, cholestatic liver injury, and PH with right-sided heart failure. With antithyroid drugs treatment, pancytopenia should resolve with euthyroidism, but PH and liver injury may take several months to resolve.


[The individual characteristics of the cytoarchitectonics of subcortical-stem formations in the human brain].
Both quantitative and qualitative analysis of individual cytoarchitectonic peculiarities of Meynart's nucleus as well as of external part of dorsomedial nucleus of thalamus was performed in mentally normal individuals. The series of brain's 20-microns sections stained with cresyl violet were studied. Some individual morphological qualitative and quantitative peculiarities were evaluated in Meynart's nucleus and in dorsomedial nucleus of thalamus. A number of pronounced cytoarchitectonic peculiarities were revealed in above-mentioned cerebral structures of the persons with outstanding abilities (the cases were taken from the special collection of Moscow Institute of Brain of Russian Academy of Medical Sciences).


Carcinoma in situ of the cervix uteri in pregnancy.
After reviewing the charts of patients at the Tulane Unit of Obstetrics and Gynecology of Charity Hospital between the years 1950 and 1970, 25 patients were noted to have carcinoma in situ of the cervix uteri associated with pregnancy. Twenty-two patients had positive Papanicolaou smears. Subsequently, 20 patients had conization of the cervix uteri to exclude an invasive lesion. Vaginal delivery was accomplished in 17 of the patients. After complete re-evaluation, definite treatment was done six to eight weeks post partum, and there were no recurrences or deaths from the disease.


[Lipids metabolism of the patients with subarachnoid hemorrhage due to ruptured intracranial aneurysm, in comparison with other cerebrovascular diseases].
Lipids metabolism has been extensively studied in the large number of patients with hypertensive cerebral hemorrhage or cerebral infarction, however, the patients with subarachnoid hemorrhage due to ruptured intracranial aneurysm were customarily excluded from the study. Total cholesterol, LDL-cholesterol, HDL-cholesterol, triglyceride and atherogenic index were determined in 40 cases, who had undergone surgical treatment for ruptured intracranial aneurysm in various locations, and the results were compared with the data obtained from 20 operative cases with hypertensive cerebral hemorrhage, 40 cases with non-operative cases with hypertensive cerebral hemorrhage, 60 cases with cerebral infarction and 20 cases of cerebral lesions other than cerebrovascular disease (non-CVA). Serum levels of LDL-cholesterol and atherogenic index were significantly correlated with the preoperative grading of subarachnoid hemorrhage when compared with non-CVA (p less than 0.05). Total cholesterol, LDL-cholesterol and atherogenic index were well correlated with operative morbidity and active daily life (ADL) in the follow-up study of the patients with intracranial aneurysm, where the higher value of cholesterol indicated the poorer risk of the patients. In our present study, none of the data was found significant, when compared with non-CVA, in the other groups of cerebrovascular diseases except for the HDL-cholesterol, which was found significantly in low level in the group of cerebral infarction (p less than 0.001). Triglyceride was found elevated in the group of hypertensive hemorrhage indicating negative correlation to the severity, and rather similar pattern was seen in the subarachnoid hemorrhage, however, the data were not conclusive.(ABSTRACT TRUNCATED AT 250 WORDS)


[Hypoglycaemia in neonates following exchange transfusion (author's transl)].
In 30 newborns the blood sugar level was determined before and after exchange transfusion. At the end of exchange transfusion, the blood sugar reached in each case 200 mg-% or more, but with in one hour fell back to the starting level. If the patient did not get an adequate quantity of sugar during that time, hypoglycaemia developed. It is known, that patients with severe haemolytic disease have hyperinsulinism, but we investigated only such patients, who were born with Hgfv levels above 10 g-%. Therefore, it seems, that the hypoglycaemia in those cases is not due to the haemolytic disease, but a reaction to the sugar, given with the ACD blood.


[Experimental work: reconstruction of the pelvi-ureteric junction and ureter using testicular tunica vaginalis autograft].
To evaluate the results of surgical reconstruction of the upper urinary tract using an autograft of testicular tunica vaginalis in experimental animals. The article presents the results of partial replacement of the renal pelvis and ureter with an autograft in 25 male dogs. The grafts were harvested by resection of the parietal layer of the testicular tunica vaginalis, which was transplanted into the region of the pelvi-ureteric junction and the proximal ureter. The upper urinary tract was drained using a ureteral stent catheter. The results were evaluated at week 1 and months 1, 3 and six after the operation. The functional state of the kidneys and ureters was analyzed using excretory urography and ultrasound; the autograft biopsy specimens were examined histologically. In all cases, the viability of the autograft was completely preserved, there were no signs of secondary infection, necrosis and impaired patency in the anastomosis zone. Histological examination revealed signs of epithelialization, connective tissue substitution and neovasculogenesis in the implantation zone. The proposed surgical modality is an alternative method to restore normal urine flow in the upper urinary tract in obstructive urological diseases. The group of obstructive urological diseases was studied using the model of the strictures of the pelvi-ureteric junction in the intrarenal pelvis and ureteral strictures measuring up to 3-4 cm in length.


Some reflections on the present situation of drug abuse among young people.
Interest in drug abuse has recently increased in Denmark and other Scandinavian countries, in particular with regard to certain aspects of the problem. This paper reviews the questions of voluntary versus compulsory treatment, the high death rate among young drug-dependent persons and the problems of the young drug-dependent woman and her child. Although it is difficult to predict future developments in drug abuse, the paper concludes that ways and means must be found to provide children and young people with a more meaningful life. This will mean tackling the social, economic and psychological situation of those at risk of becoming drug-dependent.


Rotational diffusion of calcium-dependent adenosine-5'-triphosphatase in sarcoplasmic reticulum: a detailed study.
The Ca2+-Mg2+ adenosine-5'-triphosphatase (ATPase) in sarcoplasmic reticulum has been covalently labeled with the phosphorescent triplet probe erythrosinyl 5-isothiocyanate. The rotational diffusion of the protein in the membrane at 25 degrees C was examined by measuring the time dependence of the phosphorescence emission anisotropy. Detailed analysis of both the total emission S(t) = Iv(t) + 2IH(t) and anisotropy R(t) = [Iv(t) - IH(t)]/[Iv(t) + 2IH(t)] curves shows the presence of multiple components. The latter is incompatible with a simple model of protein movement. The experimental data are consistent with a model in which the sum of four exponential components defines the phosphorescence decay. The anisotropy decay corresponds to a model in which the phosphor itself or a small phosphor-bearing segment reorients on a sub-microsecond time scale about an axis attached to a larger segment, which in turn reorients on a time scale of a few microseconds about an axis fixed in the frame of the ATPase. A fraction of the protein molecules rotate on a time scale of 100-200 microseconds about the normal to the bilayer, while the rest are rotationally stationary, at least on a sub-millisecond time scale.


Arginase inhibition protects against allergen-induced airway obstruction, hyperresponsiveness, and inflammation.
In a guinea pig model of allergic asthma, using perfused tracheal preparations ex vivo, we demonstrated that L-arginine limitation due to increased arginase activity underlies a deficiency of bronchodilating nitric oxide (NO) and airway hyperresponsiveness (AHR) after the allergen-induced early and late asthmatic reaction. Using the same animal model, we investigated the acute effects of the specific arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) and of L-arginine on AHR after the early and late reaction in vivo. In addition, we investigated the protection of allergen-induced asthmatic reactions, AHR, and airway inflammation by pretreatment with the drug. Airway responsiveness to inhaled histamine was measured in permanently instrumented, freely moving guinea pigs sensitized to ovalbumin at 24 hours before allergen challenge and after the allergen-induced early and late asthmatic reactions by assessing histamine PC(100) (provocative concentration causing a 100% increase of pleural pressure) values. Inhaled ABH acutely reversed AHR to histamine after the early reaction from 4.77 +/- 0.56-fold to 2.04 +/- 0.34-fold (P < 0.001), and a tendency to inhibition was observed after the late reaction (from 1.95 +/- 0.56-fold to 1.56 +/- 0.47-fold, P < 0.10). Quantitatively similar results were obtained with inhaled l-arginine. Remarkably, after pretreatment with ABH a 33-fold higher dose of allergen was needed to induce airway obstruction (P < 0.01). Consequently, ABH inhalation 0.5 hour before and 8 hours after allergen challenge protected against the allergen-induced early and late asthmatic reactions, AHR and inflammatory cell infiltration. Inhalation of ABH or l-arginine acutely reverses allergen-induced AHR after the early and late asthmatic reaction, presumably by attenuating arginase-induced substrate deficiency to NO synthase in the airways. Moreover, ABH considerably reduces the airway sensitivity to inhaled allergen and protects against allergen-induced bronchial obstructive reactions, AHR, and airway inflammation. This is the first in vivo study indicating that arginase inhibitors may have therapeutic potential in allergic asthma.


Stressors impair odor recognition memory via an olfactory bulb-dependent noradrenergic mechanism.
Non-associative habituation and odor recognition tasks have been widely used to probe questions of social recognition, odor memory duration, and odor memory specificity. Among others, these paradigms have provided valuable insight into how neuromodulation, and specifically norepinephrine/noradrenaline (NE) influences odor memory. In general, NE levels are modulated by arousal, stress, and behavioral state, but there is sparse evidence of a direct relationship between NE and odor memory in adult rodents. The present study uses simple mild psychological stressors (bright light and sound) to modulate NE levels physiologically in order to probe stressors NE-dependent effect on odor recognition memory. In rats with bilateral bulbar cannulations, we show that these stressors modulate olfactory memory and that this effect is at least partially mediated by the olfactory bulb. Specifically, we show that the presence of stressors during the acquisition of odor memory suppresses memory for an odor when tested 30 min after familiarization to that odor. This suppression is blocked by infusing NE antagonists into the olfactory bulb prior to odor acquisition. Additionally, we find that infusion of bulbar NE is sufficient to suppress odor memory in a manner mimicking that of our stressors. These effects are unlikely to be solely mediated by locomotor/exploratory changes produced by stressors, although these stressors influence certain behaviors not directly related to odor investigation. This study provides important information about how behaviorally relevant changes in NE can influence top-down sensory processing and odor memory.


Inhibition of lymphokine-activated killer- and natural killer-mediated cytotoxicities by neutrophils.
Peripheral blood polymorphonuclear neutrophils (PMN) can significantly inhibit lymphokine-activated killer- (LAK) mediated cytotoxicity when added to a cytotoxicity assay of IL-2-activated PBL and target cells. The inhibition by resting PMN is resistant to blocking with catalase and superoxide dismutase, suggesting that reactive oxygen species are not involved. The addition of TNF greatly enhanced the PMN-mediated inhibition of LAK effector functions. This TNF-enhanced inhibition is reversed by catalase, but not by superoxide dismutase, implicating hydrogen peroxide in the augmented inhibition. Separation of PMN from effector cells and target cells totally abrogates the inhibition by both resting PMN and TNF-treated PMN. Formalin-fixed PMN, heat-treated PMN, PMN lysates, and PMN membrane all fail to mediate any inhibition of LAK. These results suggest that contact with intact viable PMN is needed for inducing LAK inhibition. However, pretreatment of LAK cells with PMN also decreases their cytotoxicity in subsequent chromium release assays. PMN can also inhibit NK cytotoxicity of fresh PBL. However, NK activity is much less sensitive to inhibition by resting PMN than is LAK. TNF also augments PMN inhibition of NK, and there is no significant difference between LAK and NK in sensitivity to the TNF-enhanced inhibition. Our results indicate that PMN can significantly influence the destruction of tumor targets by LAK and NK, and suggest that approaches to circumvent such regulation may be important in the outcome of immunotherapies with IL-2 and LAK cells.


Triple-resonance methods for complete resonance assignment of aromatic protons and directly bound heteronuclei in histidine and tryptophan residues.
A set of three experiments is described which correlate aromatic resonances of histidine and tryptophan residues with amide resonances in 13C/15N-labelled proteins. Provided that backbone 1H and 15N positions of the sequentially following residues are known, this results in sequence-specific assignment of histidine 1H(delta2)/13C(delta2) and 1H(epsilon1)/13C(epsilon1) as well as tryptophan 1H(delta1)/13C(delta1), 1H(zeta2)/13C(zeta2), 1H(eta2)/13C(eta2), 1H(epsilon3)/13C(epsilon3), 1H(zeta3)/13C(zeta3) and 1H(epsilon1)/15N(epsilon1) chemical shifts. In the reverse situation, these residues can be located in the 1H-(15)N correlation map to facilitate backbone assignments. It may be chosen between selective versions for either of the two amino acid types or simultaneous detection of both with complete discrimination against phenylalanine or tyrosine residues in each case. The linkages between delta-proton/carbon and the remaining aromatic as well as backbone resonances do not rely on through-space interactions, which may be ambiguous, but exclusively employ one-bond scalar couplings for magnetization transfer instead. Knowledge of these aromatic chemical shifts is the prerequisite for the analysis of NOESY spectra, the study of protein-ligand interactions involving histidine and tryptophan residues and the monitoring of imidazole protonation states during pH titrations. The new methods are demonstrated with five different proteins with molecular weights ranging from 11 to 28 kDa.


Natural inactivation of a common HLA allele (A*2402) has occurred on at least three separate occasions.
HLA-A*2402 is common and widely distributed in human populations. Several individuals were identified who type genotypically for A*2402, but are serologically null for the HLA-A24 Ag. Sequencing and transfection of genomic DNA fragments containing null and wild-type A*2402 alleles, and the related A*2301 allele, revealed three different null alleles (A*2409N, A*2411N, and A*2402(low)), each of which differs from A*2402 by a single nucleotide change within the 6.7-kb sequence. The A*2301 and A*2402 sequences differ by no substitutions additional to those previously determined for the 1.1-kb cDNA. In exon 4, A*2409N has an in-frame stop codon, while A*2411N has a nucleotide insertion that alters the reading frame, causing premature termination. A*2402(low) has a nucleotide substitution near the splice acceptor site for intron 2 that impairs the production of correctly spliced mRNA. For A*2409N and A*2411N, mRNA is undetectable by Northern analysis, whereas A*2402(low) produces a low level of mRNA and a concomitant amount of normal A*2402 protein at the cell surface. The protein expressed from the A*2402(low) allele is sufficient to stimulate an alloreactive T cell response. On a background of unexpected sequence homogeneity, the single nucleotide changes in the A*2409N, A*2411, and A*2402(low) alleles have dramatic effects upon gene expression and are of likely importance for HLA matching in clinical transplantation. Segregation of at least three independently inactivated A*2402 alleles in human populations raises the possibility that loss of A*2402 may be the result of natural selection.


In vitro release of fusidic acid and teicoplanin from cancellous bone allografts.
The characteristics of cancellous bone allografts as carriers of fusidic acid and teicoplanin are described. Particles of cancellous bone were compressed into a wiremesh cylinder; five replicas were impregnated for one hour into fusidic acid; and another five for one hour into teicoplanin. Elution was estimated daily. Concentrations of fusidic acid and teicoplanin were determined by a microbiological assay. Both antibiotics were eluted at very high concentrations within the first days. Allografts impregnated in fusidic acid provided concentrations above 20 microg/ml for 20 days. Eluted teicoplanin after day 4 was below 10 microg/ml. It is concluded that cancellous bone allografts may allow adequate in vitro elution of fusidic acid but not of teicoplanin. The latter results support their application in experimental models of osteomyelitis.


Foundational Elements of Applied Simulation Theory: Development and Implementation of a Longitudinal Simulation Educator Curriculum.
Simulation-based education has gained popularity, yet many faculty members feel inadequately prepared to teach using this technique. Fellowship training in medical education exists, but there is little information regarding simulation or formal educational programs therein. In our institution, simulation fellowships were offered by individual clinical departments. We recognized the need for a formal curriculum in educational theory. Kern's approach to curriculum development was used to develop, implement, and evaluate the Foundational Elements of Applied Simulation Theory (FEAST) curriculum. Needs assessments resulted in a 26-topic curriculum; each biweekly session built upon the previous. Components essential to success included setting goals and objectives for each interactive session and having dedicated faculty, collaborative leadership and administrative support for the curriculum. Evaluation data was collated and analyzed annually via anonymous feedback surveys, focus groups, and retrospective pre-post self-assessment questionnaires. Data collected from 32 fellows over five years of implementation showed that the curriculum improved knowledge, challenged thinking, and was excellent preparation for a career in simulation-based medical education. Themes arising from focus groups demonstrated that participants valued faculty expertise and the structure, practicality, and content of the curriculum. We present a longitudinal simulation educator curriculum that adheres to a well-described framework of curriculum development. Program evaluation shows that FEAST has increased participant knowledge in key areas relevant to simulation-based education and that the curriculum has been successful in meeting the needs of novice simulation educators. Insights and practice points are offered for educators wishing to implement a similar curriculum in their institution.


Genomic distribution of three repetitive DNAs in cultivated hexaploid Diospyros spp. (D. kaki and D. virginiana) and their wild relatives.
To understand the genomic organization of Diospyros species with different ploidy levels, we cloned three different repetitive DNAs and compared their genomic distributions in ten Diospyros species, including hexaploid D. kaki and D. virginiana. Genomic Southern hybridization demonstrated that the EcoRV-repetitive DNA was present in tandem in the genomes of D. glandulosa (2n=2x=30), D. oleifera (2n=2x=30), D. lotus (2n=2x=30), D. virginiana (2n=6x=90) and D. kaki (2n=6x=90). All of these species except D. virginiana also contained the HincII-repetitive DNA in tandem. Fluorescent in situ hybridization showed that the EcoRV- and HincII-repetitive DNAs were predominantly located at the proximal or centromeric regions of chromosomes. The DraI-repetitive sequence cloned from D. ehretioides (2n=2x=30) was not found in the other Diospyros species tested. This suggests that D. ehretioides has a genomic organization different from that of the other Diospyros species. Speciation of hexaploid Diospyros species is also discussed with respect to the genomic distribution of the three repetitive DNAs cloned.


Nasal polyps in cystic fibrosis.
In II polyps from patients with cystic fibrosis of the pancreas, the density, shape, and architecture of mucous glands were studied by the whole-mount method and compared with 102 non-cystic-fibrosis polyps. There were no differences in density which was in most polyps less than 0.5 gland/mm.2. The shape and architecture as well as other histological appearances of the polyp were also alike in both groups of polyps which could not be distinguished. The pathogenesis of nasal polyps in cystic fibrosis is discussed. Apparently, it is the same as that of non-cystic-fibrosis polyps.


The impact of developing a speech and swallow rehab program: Improving patient satisfaction and multidisciplinary care.
The objective of this study was to evaluate the impact of developing an integrated head and neck cancer speech and swallowing rehabilitation program on physician/team focus on functional outcomes. Prospective cross-sectional design. Surveys regarding physician behavior and patient satisfaction with speech and swallowing were administered in an academic oncology practice prior to and 1 year following establishment of a dedicated head and neck speech and swallowing rehabilitation program. Participants included new and established head and neck cancer patients recruited consecutively. The primary outcome was physician behavior regarding speech and swallowing outcomes (as measured by discussion of function, providing suggestions regarding function, and referral to speech-language pathology services). A total of 199 surveys were returned at the first time point and 271 at the second. Demographic variables were comparable between the two groups. The later cohort was more likely to report team discussion and suggestions regarding speech and swallowing function than the former (P < .001, 95% confidence interval [CI]: -0.775 to -0.265; P < .001, 95% CI: -0.928 to -0.035, respectively). Although there was no significant difference between the groups in regard to satisfaction with speech (P = .07), more favorable satisfaction with swallowing was reported by the later cohort (P = .028, 95% CI: -0.531 to -0.029). Integration of speech and swallowing rehabilitation into head and neck cancer programs is associated with increased physician focus on functional outcomes and greater patient satisfaction in regard to swallowing function. We advocate for standard integration of such services into the multidisciplinary head and neck cancer care team. 4. Laryngoscope, 127:2578-2581, 2017.


Expression of genes that control core fucosylation in hepatocellular carcinoma: Systematic review.
Changes in N-linked glycosylation have been observed in the circulation of individuals with hepatocellular carcinoma. In particular, an elevation in the level of core fucosylation has been observed. However, the mechanisms through which core fucose is increased are not well understood. We hypothesized that a review of the literature and related bioinformatic review regarding six genes known to be involved in the attachment of core fucosylation, the synthesis of the fucosylation substrate guanosine diphosphate (GDP)-fucose, or the transport of the substrate into the Golgi might offer mechanistic insight into the regulation of core fucose levels. To survey the literature to capture the involvement of genes regulating core N-linked fucosylation in hepatocellular carcinoma. The PubMed biomedical literature database was searched for the association of hepatocellular carcinoma and each of the core fucose-related genes and their protein products. We also queried The Cancer Genome Atlas Liver hepatocellular carcinoma (LIHC) dataset for genetic, epigenetic and gene expression changes for the set of six genes using the tools at cBioportal. A total of 27 citations involving one or more of the core fucosylation-related genes (FPGT, FUK, FUT8, GMDS, SLC35C1, TSTA3) and hepatocellular carcinoma were identified. The same set of gene symbols was used to query the 371 patients with liver cancer in the LIHC dataset to identify the frequency of mRNA over or under expression, as well as non-synonymous mutations, copy number variation and methylation level. Although all six genes trended to more samples displaying over expression relative to under-expression, it was noted that a number of tumor samples had undergone amplification of the genes of the de novo synthesis pathway, GMDS (27 samples) and TSTA3 (78 samples). In contrast, the other four genes had undergone amplification in 2 or fewer samples. Amplification of genes involved in the de novo pathway for generation of GDP-fucose, GMDS and TSTA3, likely contributes to the elevated core fucose observed in hepatocellular carcinoma.


Ultrastructure of the aging myocardium: a morphometric approach.
Left ventricular tissue from adult and aging Syrian hamster heart was compared at the ultrastructural level, using both qualitative and morphometric electron microscopy. The aging myocardium often showed indented nuclei, lipid droplets and aggregations of dense bodies. The volume fractions of muscle cells occupied by mitochondria, lipid and lysosomes (including both primary lysosomes and residual bodies) was significantly greater in the old animals, while there was no significant difference in nuclear volume fraction or myofibrillar mass. Sarcoplasmic reticular volume and membrane surface area fell during aging. The area of mitochondrial inner membrane plus cristae per mitochondrial volume also fell. When sarcoplasmic reticular and mitochondrial area were expressed per myofibrillar volume fraction, the sarcoplasmic reticular ratio fell, while the mitochondrial parameter remained constant. Discoordinate aging of cellular components in the mammalian myocardium is proposed.


Laparoscopic Roux-en-"W" gastric bypass.
Roux-en-Y gastric bypass is the gold standard for treating morbid obesity in this country. The totally laparoscopic performance of this procedure, although quite demanding and technically difficult, has revolutionized it; and the demand for it has skyrocketed. We describe 2 cases where it became necessary to convert the Y into a "W" while performing the procedure. A laparoscopic Roux-en-Y gastric bypass was attempted on 2 patients, 1 male and 1 female, both with body mass indexes greater than 40. During creation of the side to side jejunojejunostomy, ie, the Y, it became obvious that stenosis or obstruction would result. This area was partially resected and an additional side to side anastomosis was formed, creating a "W." The operative time was 205 minutes and 180 minutes, respectively, which compared favorably with the average operative time of 151 minutes in that quartile of patients (patients #101-#150). Both patients had normal upper gastrointestinal and small bowel contrast x-rays the day following surgery and were started on clear liquids. They were discharged later that day. Weight loss of 119 lb at 8 months and 80 lb at 6 months was documented, respectively, with no gastrointestinal sequelae. If problems are encountered when creating the Y of a laparoscopic Roux-en-Y gastric bypass, a laparoscopic Roux-en-W may be performed. It appears safe, technically feasible, and with a postoperative course not unlike that of the standard approach.


Monolayers of hard rods on planar substrates. II. Growth.
Growth of hard-rod monolayers via deposition is studied in a lattice model using rods with discrete orientations and in a continuum model with hard spherocylinders. The lattice model is treated with kinetic Monte Carlo simulations and dynamic density functional theory while the continuum model is studied by dynamic Monte Carlo simulations equivalent to diffusive dynamics. The evolution of nematic order (excess of upright particles, "standing-up" transition) is an entropic effect and is mainly governed by the equilibrium solution, rendering a continuous transition [Paper I, M. Oettel et al., J. Chem. Phys. 145, 074902 (2016)]. Strong non-equilibrium effects (e.g., a noticeable dependence on the ratio of rates for translational and rotational moves) are found for attractive substrate potentials favoring lying rods. Results from the lattice and the continuum models agree qualitatively if the relevant characteristic times for diffusion, relaxation of nematic order, and deposition are matched properly. Applicability of these monolayer results to multilayer growth is discussed for a continuum-model realization in three dimensions where spherocylinders are deposited continuously onto a substrate via diffusion.


Using digital surveillance to examine the impact of public figure pancreatic cancer announcements on media and search query outcomes.
Announcements of cancer diagnoses from public figures may stimulate cancer information seeking and media coverage about cancer. This study used digital surveillance to quantify the effects of pancreatic cancer public figure announcements on online cancer information seeking and cancer media coverage. We compiled a list of public figures (N = 25) who had been diagnosed with or had died from pancreatic cancer between 2006 and 2011. We specified interrupted time series models using data from Google Trends to examine search query shifts for pancreatic cancer and other cancers. Weekly media coverage archived on Google News were also analyzed. Most public figures' pancreatic cancer announcements corresponded with no appreciable change in pancreatic cancer search queries or media coverage. In contrast, Patrick Swayze's diagnosis was associated with a 285% (95% confidence interval [CI]: 212 to 360) increase in pancreatic cancer search queries, though it was only weakly associated with increases in pancreatic cancer media coverage. Steve Jobs's death was associated with a 197% (95% CI: 131 to 266) increase in pancreatic cancer queries and a 3517% (95% CI: 2882 to 4492) increase in pancreatic cancer media coverage. In general, a doubling in pancreatic cancer-specific media coverage corresponded with a 325% increase in pancreatic cancer queries. Digital surveillance is an important tool for future cancer control research and practice. The current application of these methods suggested that pancreatic cancer announcements (diagnosis or death) by particular public figures stimulated media coverage of and online information seeking for pancreatic cancer.


Arachidonate 12-lipoxygenase of platelet-type in human epidermal cells.
A homogenate of epidermal cells isolated from human skin converted arachidonic acid to 12S-hydroxy-5, 8,10,14-eicosatetraenoic acid and 15-hydroxy-5, 8,11,13-eicosatetraenoic acid as the main lipoxygenase products. The production of these hydroxy acids was not stimulated by the addition of 1 mM NADPH required for cytochrome P-450 reaction, but inhibited by 65-75% with 40 microM nordihydroguaiaretic acid, a nonspecific lipoxygenase inhibitor. In addition to these lipoxygenase products, the epidermal cell homogenate converted arachidonic acid to prostaglandin E2 together with minor amounts of prostaglandins D2 and F2a and 12-hydroxy-5,8,10-heptadecatrienoic acid. Thromboxane B2 was not detected. This finding rules out the possible contamination of platelet 12-lipoxygenase in the epidermal cells. After subcellular fractionation of the epidermal cell homogenate, the 12-lipoxygenase activity was found in the 164,000 x g supernatant, the 164,000 x g pellet, and the 10,000 x g pellet. The cytosolic enzyme and the enzymes solubilized from the two pellets produced 12S-hydroperoxy-5,8,10,14-eicosatetraenoic acid as the primary product in contrast to cytochrome P-450 which produces primarily hydroxy acids. The 12-lipoxygenase in the 164,000 x g supernatant and the solubilized enzymes from the 164,000 x g pellet and 10,000 x g pellet were precipitable by antibodies raised against human platelet 12-lipoxygenase, but not by antibodies against porcine leukocyte 12-lipoxygenase. The immunoprecipitated 12-lipoxygenase from each fraction was almost inactive with linoleic acid as substrate, characteristic of 12-lipoxygenase of platelet-type. Furthermore, 12-lipoxygenase mRNA in the epidermal cells could be reverse-transcribed and amplified by polymerase chain reaction with the primers specific for human platelet 12-lipoxygenase cDNA, but not with those for porcine leukocyte 12-lipoxygenase cDNA. Thus, the 12-lipoxygenase of human epidermal cells is similar to human platelet 12-lipoxygenase in terms of immunogenicity, catalytic property, and primary structure, and distinct from leukocyte 12-lipoxygenase.


The spectrum of renal diseases with lupus-like features: a single-center study.
A subset of patients without overt systemic lupus erythematosus (SLE) present with biopsy findings typically seen in lupus nephritis (LN). Although a minority eventually develops SLE, many do not. It remains unclear how to classify or treat these patients. Our study attempted to further understand the clinical and pathological characteristics of cases with lupus-like nephritis (LLN). Among 2700 native kidney biopsies interpreted at University of Rochester Medical Center (URMC) from 2010 to 2019, we identified 27 patients with biopsies showing lupus-like features (LL-fx) and 96 with LN. Of those with LL-fx, 17 were idiopathic LLN and 10 were associated with a secondary etiology (e.g., infection/drugs). At the time of biopsy, the LLN-group tended to be slightly older (44 vs. 35), male (58.8 vs. 17.7%, p = .041), and Caucasian (47.0 vs. 28.1%, p = .005). Chronic kidney disease was the most common biopsy indication in LLN (21.4 vs. 2.8%, p = .001). Both LN and LLN presented with nephrotic-range proteinuria (mean 5.73 vs. 4.40 g/d), and elevated serum creatinine (mean 1.66 vs. 1.47 mg/dL). Tubuloreticular inclusions (TRIs; p < .001) and fibrous crescents (p = .04) were more often seen in LN, while more tubulointerstitial scarring was seen in LLN (p = .011). At mean follow-up of 1684 d (range: 31-4323), none of the LLN patients developed ESRD. A subset of both LN and cases with LL-fx overlapped with other autoimmune diseases. Lupus-like pathologic features are seen in a wide array of disease processes. The findings suggest that LLN may be a manifestation of an autoimmune process that overlaps with SLE.


Molecular, transcriptional and functional insights into duplicated goose-type lysozymes from Sebastes schlegelii and their potential immunological role.
Black rockfish (Sebastes schlegelii), an important aquaculture species in Korea, has been affected by bacterial diseases leading to a drastic decline in production. Goose-type lysozyme (LysG) is a key enzyme of the innate immune system to eradicate bacterial infections. In this study, two isoforms of LysG from black rockfish, designated as RfLysG1 and RfLysG2, have been identified and characterized at the molecular, transcriptional, and functional levels. The deduced amino acid sequences had the LysG family characteristics and exhibited conserved properties, including active residues and domains. The cDNA sequences of RfLysG1 and RfLysG2 were 1514 bp and 900 bp in length, respectively. The 567-bp open reading frame (ORF) of RfLysG1 encoded a protein of 188 amino acids with molecular mass 20.11 kDa, and the 600-bp ORF of RfLysG2 encoded a polypeptide with 199 amino acids and molecular mass of 22.19 kDa. Homology studies indicated that RfLysG1 showed the highest identity (84.6%) with LysG-B of Oplegnathus fasciatus, while RfLysG2 showed the highest identity (74.4%) with LysG of Siniperca chuatsi. Both sequences possessed a soluble lytic trans-glycosylase domain. Both lacked signal peptide and they were not identified as proteins secreted by non-classical pathway by the SecretomeP server. Transcriptional analysis of the two genes showed constitutive expression, where both genes were highly expressed in blood under normal physiological conditions. In response to the immune challenges lipopolysaccharide (LPS), Streptococcus iniae, and poly I:C injection, the expression of RfLysG1 and RfLysG2 was significantly upregulated in blood and spleen tissues in a time-dependent manner. Turbidimetric assays indicated that both recombinant proteins tagged with maltose-binding protein (MBP) were reactive against several Gram-positive and Gram-negative bacteria, but MBP was inactive. Optimum temperatures for the recombinant RfLysG1 and RfLysG2 were 40 °C and 50 °C, respectively, and both were highly active at pH 3.0. The results provide evidence for the vital immunological role and bacteriolytic potential of RfLysG1 and RfLysG2.


Structure of the Plexin Ectodomain Bound by Semaphorin-Mimicking Antibodies.
Semaphorin family proteins act on cells to mediate both repulsive and attractive guidance via binding to plexin family receptors, thereby playing fundamental roles in the morphogenesis and homeostasis of various tissues. Although semaphorin-plexin signaling is implicated in various diseases and is thus a target of intensive research, our mechanistic understanding of how semaphorins activate plexins on the cell surface is limited. Here, we describe unique anti-plexin-A1 antibodies that can induce a collapsed morphology in mouse dendritic cells as efficiently as the semaphorin 3A (Sema3A) ligand. Precise epitope analysis indicates that these "semaphorin-mimicking" antibodies dimerize cell-surface plexin-A1 by binding to the N-terminal sema domain of the plexin at sites away from the interface used by the Sema3A ligand. Structural analysis of plexin-A1 fragments using negative stain electron microscopy further revealed that this agonistic capacity is closely linked to the location and orientation of antibody binding. In addition, the full-length plexin-A1 ectodomain exhibited a highly curved "C" shape, reinforcing the very unusual dimeric receptor conformation of this protein at the cell surface when engaged with Sema3A or agonistic antibodies.


The 1H NMR method for the determination of the absolute configuration of 1,2,3-prim,sec,sec-triols.
The absolute configuration of 1,2,3-prim,sec,sec-triols can be assigned by comparison of the 1H NMR spectra of the tris-(R)- and the tris-(S)-MPA ester derivatives. An experimental demonstration of this correlation with 24 triols of known absolute configuration and a protocol using two parameters-Deltadelta(RS)(H3) and the difference between Deltadelta RS (H2) and Deltadelta RS (H3) = absolute value (Delta(Deltadelta RS))-for its application to the determination of the absolute configuration of other triols are presented.


Sulforaphane Improves Abnormal Lipid Metabolism via Both ERS-Dependent XBP1/ACC &SCD1 and ERS-Independent SREBP/FAS Pathways.
To investigate the effect of sulforaphane (SFN) on the abnormal lipid metabolism and underlying mechanisms. Models with abnormal lipid metabolism are established both in rats and human hepatocytes. Hepatic steatosis is detected by hematoxylin and eosin and oil red O staining. The structure of endoplasmic reticulum is visualized by transmission electron microscopy. The expressions of X-box binding protein 1 (XBP1), protein kinase-like ER kinase (PERK), sterol regulatory element binding protein-1c (SREBP1c), and lipogenic enzymes are determined by real-time PCR and western blot analysis. SFN lowers the content of triglyceride and cholesterol. SFN alleviates the swelling of ER and decreases the perimeter of ER. SFN significantly decreases the expressions of acetyl CoA carboxylase 1 (ACC1), stearoyl-CoA desaturase 1 (SCD1), and fatty acid synthase. SFN inhibits SREBP1c by blocking the PERK. Meanwhile, SFN suppresses ACC1 and SCD1 via blocking the formation of splicing-type XBP1. The key roles of XBP1 and SREBP1c in SFN-reduced lipid droplets are confirmed by a timed sequence of measurement according to time points. SFN improves abnormal lipid metabolism via both ER-stress-dependent and -independent pathways.


Risk Factors for Thyroid Cancer in Females Using a Logit Model in Lahore, Pakistan.
Thyroid cancer (TC) is a more common endocrine malignancy in females and is a major cause of death in developing countries. Therefore the aim of this study was to explore possible risk factors of thyroid cancer in females of Pakistan. This study covered 232 females, including 127 (54.7%) cases and 105 (45.2%) controls, from the INMOL Hospital and Sheikh Zayed Hospital, Lahore. Different risk factors were explored by the descriptive and inferentially statistics. Odds ratios and 95% confidence intervals for different risk factors were computed using logistic regression. The results showed six risk factors, marital status, family history of thyroid cancer, iodine in the diet, oxidative stress, fast food and fried food, to demonstrate positive significant links to thyroid cancer (odds ratios and 95% confidence intervals of :2.152, 1.104-4.198; 2.630, 1.416-4.887; 2.391, 1.282-4.458; 4.115, 2.185-7.750; 3.656, 1.851-7.223; 2.357, 1.268-4.382; and 2.360, 1.199-4.643, respectively). The Oxidative stress, marital status, family history of cancer, fast food, use of iodine diet and fried food are the risk factors of thyroid cancer in females.


Parental strand recognition of the DNA replication origin by the outer membrane in Escherichia coli.
The outer membrane of Escherichia coli binds the origin of DNA replication (oriC) only when it is hemimethylated. We report here the results of a footprinting analysis with the outer membrane which demonstrate that its interaction with oriC occurs mainly at the left moiety of the minimal oriC, where 10 out of 11 Dam methylation sites are concentrated. Two regions, flanking the Integration Host Factor (IHF) sites, are preferentially recognized at the minimum membrane concentration at which oriC plasmid replication is inhibited in vitro. We have identified the putative proteins involved in hemimethylated oriC binding and cloned one of the corresponding genes (hobH). The purified LacZ-HobH fusion protein specifically binds oriC DNA at the same preferential sites as the membrane. A mutant of the hobH gene reveals partial asynchronous initiation of DNA replication.


Monopolar electrodissection versus cold dissection tonsillectomy among children.
To compare cold dissection to monopolar tonsillectomy in terms of operative time, intraoperative bleeding, post operative bleeding, and pain. The study included 100 children who underwent tonsillectomy between January 2002 and January 2004. This study was carried out at King Abdul-Aziz University Hospital, Riyadh, Kingdom of Saudi Arabia. Patients were randomly selected to have either the right or left tonsils removed by either technique (cold dissection or monopolar dissection technique). We compared both techniques in each side on the same patient. There was no significant difference in operative time between both sides by either technique, however, when the patients were grouped into < or =3 minutes and >3 minute groups, the result showed that a greater number of patients were operated up on < or =3 minutes by diathermy procedure compared to dissection method (44 versus 67) (p=0.0011). Blood loss was minimal with the diathermy technique; averaging 25.37 ml compared to 88.5 ml for cold dissection tonsillectomy. There was a significant increase in postoperative pain on the first postoperative day in the diathermy group compared to the cold dissection group (27% versus 12%) (p=0.0151). However, there was no significant difference in pain between both sides in the first 24 hours and from the 2nd to 10th postoperative days. Monopolar dissection tonsillectomy is a safe technique. It significantly reduces the operative time and intraoperative blood loss. However, it causes more pain on the 1st post operative day, while on the rest of the days until the 10th post operative day, there was no significant difference in pain between two sides.


Distance education project of English idioms learning from watching YouTube.
Idioms have been recognized to be commonly adopted by academic practitioners in their speech and writing. However, despite their common occurrence in English communication, idioms pose great challenges for non-native English speakers, as they are often ignored in English classrooms. Particularly in Vietnam, a minimal number of idioms appear in English textbooks published by the Ministry of Education, and teachers appeared to under-emphasize English idioms' usefulness in conversation. To fill the gap, the present study adopted YouTube for Vietnamese students to undertake supplementary learning of English idiom knowledge. The study recruited 34 students and randomly assigned them to a control group and an experimental group. Both groups were required to take notes during their watching. Yet, only the experimental group would take extra exercises at the end of their watching. Immediate post-tests, delayed post-tests, and a survey were conducted. The findings demonstrate that the students in the two groups retained idiom knowledge similarly well. They were also positive towards learning English idioms through YouTube. Pedagogical implications and research suggestions are provided to conclude the study.


Baroreflex Coupling Assessed by Cross-Compression Entropy.
Estimating interactions between physiological systems is an important challenge in modern biomedical research. Here, we explore a new concept for quantifying information common in two time series by cross-compressibility. Cross-compression entropy (CCE) exploits the ZIP data compression algorithm extended to bivariate data analysis. First, time series are transformed into symbol vectors. Symbols of the target time series are coded by the symbols of the source series. Uncoupled and linearly coupled surrogates were derived from cardiovascular recordings of 36 healthy controls obtained during rest to demonstrate suitability of this method for assessing physiological coupling. CCE at rest was compared to that of isometric handgrip exercise. Finally, spontaneous baroreflex interaction assessed by CCEBRS was compared between 21 patients suffering from acute schizophrenia and 21 matched controls. The CCEBRS of original time series was significantly higher than in uncoupled surrogates in 89% of the subjects and higher than in linearly coupled surrogates in 47% of the subjects. Handgrip exercise led to sympathetic activation and vagal inhibition accompanied by reduced baroreflex sensitivity. CCEBRS decreased from 0.553 ± 0.030 at rest to 0.514 ± 0.035 during exercise (p < 0.001). In acute schizophrenia, heart rate, and blood pressure were elevated. Heart rate variability indicated a change of sympathovagal balance. The CCEBRS of patients with schizophrenia was reduced compared to healthy controls (0.546 ± 0.042 vs. 0.507 ± 0.046, p < 0.01) and revealed a decrease of blood pressure influence on heart rate in patients with schizophrenia. Our results indicate that CCE is suitable for the investigation of linear and non-linear coupling in cardiovascular time series. CCE can quantify causal interactions in short, noisy and non-stationary physiological time series.