Neutron interferometry using a single modulated phase grating.
Neutron grating interferometry provides information on phase and small-angle scatter in addition to attenuation. Previously, phase grating moiré interferometers (PGMI) with two or three phase gratings have been developed. These phase-grating systems use the moiré far-field technique to avoid the need for high-aspect absorption gratings used in Talbot-Lau interferometers (TLI) that reduce the neutron flux reaching the detector. We first demonstrate, through theory and simulations, a novel phase grating interferometer system for cold neutrons that requires a single modulated phase grating (MPG) for phase-contrast imaging, as opposed to the two or three phase gratings in previously employed PGMI systems. The theory shows the dual modulation of MPG with a large period and a smaller carrier pitch P, resulting in large fringes at the detector. The theory was compared to the full Sommerfeld-Rayleigh diffraction integral simulator. Then, we proceeded to compare the MPG system to experiments in the literature that use a two-phase-grating-based PGMI with best-case visibility of around 39%. The simulations of the MPG system show improved visibility in comparison to that of the two-phase-grating-based PGMI. An MPG with a modulation period of 300 µm, the pitch of 2 µm, and grating heights with a phase modulation of (π,0, illuminated by a monochromatic beam produces visibility of 94.2% with a comparable source-to-detector distance (SDD) as the two-phase-grating-based PGMI. Phase sensitivity, another important performance metric of the grating interferometer, was compared to values available in the literature, viz. the conventional TLI with the phase sensitivity of 4.5 × 103 for an SDD of 3.5 m and a beam wavelength of 0.44 nm. For a range of modulation periods, the MPG system provides comparable or greater theoretical maximum phase sensitivity of 4.1 × 103 to 10.0 × 103 for SDDs of up to 3.5 m. This proposed MPG system appears capable of providing high-performance PGMI that obviates the need for the alignment of two phase gratings.


Waterproof, thin, high-performance pressure sensors-hand drawing for underwater wearable applications.
Wearable sensors, especially pressure sensors, have become an indispensable part of life when reflecting human interactions and surroundings. However, the difficulties in technology and production-cost still limit their applicability in the field of human monitoring and healthcare. Herein, we propose a fabrication method with flexible, waterproof, thin, and high-performance circuits - based on hand-drawing for pressure sensors. The shape of the sensor is drawn on the pyralux film without assistance from any designing software and the wet-tissues coated by CNTs act as a sensing layer. Such sensor showed a sensitivity (~0.2 kPa-1) while ensuring thinness (~0.26 mm) and flexibility for touch detection or breathing monitoring. More especially, our sensor is waterproof for underwater wearable applications, which is a drawback of conventional paper-based sensors. Its outstanding capability is demonstrated in a real application when detecting touch actions to control a phone, while the sensor is dipped underwater. In addition, by leveraging machine learning technology, these touch actions were processed and classified to achieve highly accurate monitoring (up to 94%). The available materials, easy fabrication techniques, and machine learning algorithms are expected to bring significant contributions to the development of hand-drawing sensors in the future.


[Influence of the middle ear on the measurement of otoacoustic emissions].
Otoacoustic emissions (OAEs) provide an objective, non-invasive measurement of cochlear function. OAEs have proven to have a high sensitivity and reasonable specificity for hearing impairment diagnosis, especially when used for infant screening. The lower specificity could be due to middle ear function and that this affects otoacoustic emissions. We have carried out a study in 1,202 ears with a mean age of 6.2 years. Clinical otoscopy and OAE measurements were performed in all cases and tympanometry in those cases with a negative result in the recorded emissions. Statistical analysis of tympanogram type indicated significant association with tympanogram type B and the absence of OAEs, as well as with otoscopic findings of secretory otitis media. Middle ear function must be taken into consideration when OAEs are used in clinical application. The problem of low specificity is mainly due to the fact that middle ear function affects the presence or absence of emissions with normal cochlear function.


Properties of the B oligomer of pertussis toxin.
The B oligomer of pertussis toxin was purified from culture supernatants of Bordetella pertussis strains which do not secrete the S1 subunit. The purified B oligomer is devoid of toxicity for CHO cells and other in vivo properties of the toxin, such as leukocytosis and histamine sensitization, but it retains the abilities to agglutinate erythrocytes and to induce the proliferation of T lymphocytes. The B oligomer is also able to induce protective immunity in mice but is less potent than molecules containing the S1 subunit also.


Corticosteroid treatment of refractory Kawasaki disease.
To review the indications for corticosteroids in patients with Kawasaki disease (KD) treated by pediatric rheumatologists in Canada and to determine their efficacy on fever in patients with refractory KD. All practicing pediatric rheumatologists in Canada identified KD patients treated with corticosteroids and completed a standard data form that included demographics, clinical and laboratory features, imaging studies, and therapeutic interventions, by chart review. Thirty-two patients with KD (14 female; 18 male: mean age 4.6 years) were treated with corticosteroids. Corticosteroids were used in 26 patients (81%) for persistent fever despite treatment with intravenous immunoglobulin (IVIG) (refractory KD), 5 patients (19%) for congestive heart failure, and 1 patient for persistent acute phase symptoms other than fever. The 26 patients with refractory KD are the primary subject of this report. Twenty-two patients (85%) had rapid, sustained resolution of fever after corticosteroids. There were no serious reported adverse effects. Eight patients (31%) treated with corticosteroids developed coronary artery (CA) aneurysms and 9 (35%) developed CA dilatations without aneurysms. Of those who developed CA aneurysm, 4 had aneurysms detected prior to IV methylprednisolone (MP) on echocardiograms performed on days 6-27 (mean day 13) of illness. The remaining 4 patients had CA aneurysm detected after IVMP therapy, on echocardiograms performed on days 13-49 (mean day 23) of illness, 1-25 days (mean 9 days) after IVMP. In patients with one year or more of followup, 46% had resolution of CA abnormalities. Corticosteroids are effective in the treatment of fever in most patients with IVIG-refractory KD. A multicenter prospective study is needed to determine the effect of corticosteroids on CA outcome in patients with refractory KD.


Upregulation of NMDARI mRNA induced by MK-801 is associated with massive death of axotomized motor neurones in adult rats.
Studies on the pathogenesis of human motor neurone disease have suffered from the absence of models of motor neurone degeneration in adult animals. Normally in adult rodents, transection of motor neurone axons results in only a modest degree of neuronal death. We reasoned that axotomy-induced motor neurone death might be enhanced by modulating glutamatergic transmission. By axotomizing the facial nerve in adult rats and then administering MK-801 for the first week of a 4-week or 8-week post-lesion survival period, we induced a 67% motor neurone loss by 8 weeks as compared with a 19% loss in controls. A possible explanation for the increased motor neurone loss after MK-801 treatment is that transient blockade of NMDA receptors may upregulate synthesis of NMDA receptor components. In order to test this idea, we employed quantitative in situ hybridization to determine the response of NMDAR1 mRNA to axotomy and axotomy + MK-801 treatment. Quantification of the percentage of area occupied by NMDAR1 silver grains per motor neurone somata indicated that axotomy alone did not provoke a change in NMDAR1 mRNA. However, axotomy and MK-801 combined treatment resulted in a highly significant upregulation of NMDAR1 mRNA when compared with controls or animals treated solely with axotomy. Our results suggest that motor neurone death in adult animals can be enhanced after axotomy in association with the upregulation of NMDA receptor mRNA. Thus, abnormalities in glutamate receptor signalling may lead to subacute motor neurone death in vivo. Furthermore these results indicate that transient treatment with MK-801 is a convenient method for enhancing the degree of motor neurone death after axotomy in adult animals.


Preoperative plasma plasminogen activator inhibitor type-1 and serum C-reactive protein levels in patients with colorectal cancer. The RANX05 Colorectal Cancer Study Group.
Preoperative plasma plasminogen activator inhibitor-1 (PAI-1) is a prognostic variable in patients with colorectal cancer. It has been suggested, however, that plasma PAI-1 is a nonspecific prognostic parameter similar to the acute-phase reactant C-reactive protein (CRP). In the present study we analyzed the association between plasma PAI-1 and serum CRP in patients scheduled for elective resection of colorectal cancer. In addition, the prognostic value of PAI-1 and CRP was studied in this patient cohort. PAI-1 and CRP were analyzed in citrated plasma and serum, respectively, obtained preoperatively from 594 patients. Patients who required preoperative blood transfusion received SAGM blood, in which soluble PAI-1 is not present. None of the patients received pre- or postoperative adjuvant chemotherapy, and all were followed in the outpatient clinic for at least 5 years or until death. The association of PAI-1 and CRP, respectively, with survival was tested using the median value of PAI-1 and the upper normal limit for CRP. Analyses were performed by inclusion of all patients, and in the subgroup of patients, who underwent curative resection. The median follow-up period was 6.8 (5.4-7.9) years. The median value of plasma PAI-1 was 35.8 ng/ml, and values greater than 94 nmol/L identified patients with increased CRP levels. Comparison of the molecules showed that PAI-1 was weakly correlated with CRP (r = .26; P <.0001). Both molecules showed a Dukes independent distribution. In univariate survival analyses high levels of PAI-1 were found associated with poor prognosis and low levels with good prognosis (P = .02, HR: 1.3). Similarly, high levels of CRP were found associated with poor prognosis and low levels with good prognosis (P <.0001, HR: 1.9). In a multivariate statistical analysis including Dukes classification, gender, age, tumor location, perioperative blood transfusion, PAI-1 and CRP, plasma PAI-1 was a dependent prognostic variable, while serum CRP (P <.0001; HR: 1.4; 95% CI: 1.3-1.5) was found to be a Dukes independent prognostic variable. Similar analyses, excluding patients with Dukes' D disease showed serum CRP to be an independent prognostic variable (P <.0001; HR: 1.3: 95% CI: 1.2-1.5). This study did not show a strong correlation between plasma PAI-1 and serum CRP in patients with colorectal cancer. Serum CRP was found to be a Dukes independent prognostic variable in this patient cohort, and was found to identify a subgroup of curatively resected patients at risk for short survival.


Fetal ultrasound scan--prerogatives for the basic level.
Adequate level of prenatal ultrasound scan is a prerequisite for a successful definition of high risk population that needs further investigations. "Basic", standardized fetal mid-trimester scan, with an informative report enables not only diagnosis of anomaly but also evaluation of state of pregnancy in general. This paper was aimed at reviewing the benefits of and requirements for a complete basic mid-trimester fetal ultrasound scan and the necessary documentation. Potential directions for development of organization of basic mid-trimester fetal ultrasound scans are standardization of the scan, with establishing the number and the level of examination, and continual education of both the doctors and the patients. In order to standardize the exam, a uniform check list is needed, so that the examination should always be done in the same manner and at the same level, no matter where it is done and by whom. International and national guidelines should be agreed upon and they should state clear standards on who should do the scan, how, what kind of ultrasound machine should be used and what documentation should be kept. This paper presents a possible standardization of basic level mid trimester fetal ultrasound scan. A routine complete second trimester ultrasound between 18 and 22 weeks and a complete ultrasound report will provide the best opportunity to diagnose fetal anomalies and to help in the management of prenatal care. It will also reduce the unnecessary number of ultrasound examinations done during the second trimester for completion of fetal anatomy survey, which would decrease the costs.


Structural and Electronic Properties of Iron-Doped Sodium Montmorillonite Clays: A First-Principles DFT Study.
First-principles calculations done via density functional theory were used to study the structural and electronic properties of sodium montmorillonite clay (Mt-Na+) of general formula M x Al3Si8O24H4Na·nH2O (M x : Mg or Fe). The final position of the interlamellar sodium atom is found to be close to the oxygen atoms located on the upper surface of silica. Following Fe-Mt-Na+ system relaxation, with subsequent analysis of magnetic moment and magnetic states, the electroneutrality of the system established that both Fe2+ and Fe3+ oxidation states are possible to occur. The Mg2+-Mt-Na+ material shows a band gap energy greater than that of Fe2+-Mt-Na+ when iron is in the octahedral site. It is found that the valence-band maximum and the conduction-band minimum of iron-doped montmorillonite are both at the Γ-point, while it is at V → Γ for magnesium-doped montmorillonite. The calculated band gap from hybrid functional (HSE06) of Fe2+-Mt-Na+ is equal to 4.3 eV, exhibiting good agreement with experimental results obtained from ultraviolet-visible spectroscopy of the natural Mt-Na+ (Cloisite-Na+).


An Accurate Fiducial Marker for Aligning EMG signals with Swallow Onset.
Swallowing involves the precise coordination of a large number of muscles. This coordination can be quantified non-invasively by electromyographic (EMG) time-series analysis of swallowing events. The temporal alignment of swallow events is critical for defining coordination patterns. Here, a new framework was developed to use the acoustic signal associated with the opening of the Eustachian tube as a fiducial marker to align EMG signals with swallowing. To investigate its accuracy, manometry, audio from the Eustachian tube, and EMG were simultaneously recorded from two participants while performing different swallowing maneuvers. Eustachian tube opening consistently occurred alongside EMG activations and within 0.025 ± 0.022 s of the gold standard manometry-determined functional swallowing onset. A comparison with two traditional EMG alignment methods based on the integrated and rectified EMG signals was then performed over eight participants. Discrepancies of between 0.2 to 0.3 s were found between the initiation of swallowing and the onset or peak EMG activity. Eustachian tube opening served as a more accurate fiducial marker for temporal data alignment, compared to the traditional EMG alignment methods that were based on EMG parameters.Clinical Relevance- The proposed method will allow EMG recordings to be directly associated with the functional onset of swallowing. This provides a more accurate foundation for time-series analysis of muscle coordination and thus the identification of EMG biomarkers associated with healthy and dysphagic swallowing.


Biology and evolution of the endogenous koala retrovirus.
Although endogenous retroviruses are ubiquitous features of all mammalian genomes, the process of initial germ line invasion and subsequent inactivation from a pathogenic element has not yet been observed in a wild species. Koala retrovirus (KoRV) provides a unique opportunity to study this process of endogenisation in action as it still appears to be spreading through the koala population. Ongoing expression of the endogenous sequence and consequent high levels of viraemia have been linked to neoplasia and immunosuppression in koalas. This apparently recent invader of the koala genome shares a remarkably close sequence relationship with the pathogenic exogenous Gibbon ape leukaemia virus (GALV), and comparative analyses of KoRV and GALVare helping to shed light on how retroviruses in general adapt to a relatively benign or at least less pathogenic existence within a new host genome. (Part of a multi-author review).


The prognostic implication of the basal-like (cyclin E high/p27 low/p53+/glomeruloid-microvascular-proliferation+) phenotype of BRCA1-related breast cancer.
Previous studies have shown that BRCA1-related breast cancers are often high-grade tumors that do not express estrogen receptors, HER2, p27(Kip1), or cyclin D1, but do express p53 and cyclin E. In addition, the expression of cytokeratin 5/6 (CK5/6), indicating a basal epithelial phenotype, is frequent in BRCA1-related breast cancer. Here, in a series of 247 breast cancers, we demonstrate that CK5/6 expression was associated with nearly all of the features of BRCA1-related breast cancer and was also associated with a poor prognosis. In a parsimonious multivariable proportional hazards model, protein levels of cyclin E, p27(Kip1), p53, and the presence of glomeruloid microvascular proliferation all independently predicted outcome after breast cancer. In this model, only cyclin E and p27(Kip1) levels were independent predictors in lymph node-negative cancers, whereas glomeruloid microvascular proliferation and tumor size independently predicted outcome in node-positive disease. The molecular determinants of the basal epithelial phenotype encapsulate many of the key features of breast cancers occurring in germ-line BRCA1 mutation carriers and have independent prognostic value. Basal breast cancer deserves recognition as an important subtype of breast cancer.


Ultralow Ru Single Atoms Confined in Cerium Oxide Nanoglues for Highly-Sensitive and Robust H2 O2 -Related Biocatalytic Diagnosis.
Exploring highly efficient, portable, and robust biocatalysts is a great challenge in colorimetric biosensors. To overcome the challenging states in creating single-atom biocatalysts, such as insufficient activity and stability, here, this work has engineered a unique CeO2 support as nanoglue to tightly anchor the Ru single-atom sites (CeO2 -Ru) with strong electronic coupling for achieving highly sensitive and robust H2 O2 -related biocatalytic diagnosis. The morphology and chemical/electronic structure analysis demonstrates that the Ru atoms are well-dispersed on CeO2 surface to form high-density active sites. Benefiting from the unique structure, the prepared CeO2 -Ru exhibits outstanding peroxidase (POD) like catalytic activity and selectivity to H2 O2 . Steady-state kinetic study results show that the CeO2 -Ru presents the highest Vmax and turnover number than the state-of-the-art POD-like biocatalysts. Consequently, the CeO2 -Ru discloses a high efficiency, good selectivity, and robust stability in the colorimetric detection of L-cysteine, glucose, and uric acid. Notably, the limit of detection (LOD) can reach 0.176 × 10-3 m for the L-cysteine, 0.095 × 10-3 m for the glucose, and 0.088 × 10-3 m for the uric acid via cascade reaction. This work suggests that the proposed unique CeO2 nanoglue will offer a new path to create single-atom noble metal biocatalysts and take a step closer to future biotherapeutic and biocatalytic applications.


Gel-based proteomics reveals potential novel protein markers of ozone stress in leaves of cultivated bean and maize species of Panama.
We examined responses of cultivated bean (Phaseolus vulgaris L. cv. IDIAP R-3) and maize (Zea mays L. cv. Guarare 8128) plants exposed to ozone (O(3)) using a leaf injury assessment and proteomics approach. Plants grown for 16 days in greenhouse were transferred to an O(3) chamber and exposed continuously to 0.2 ppm O(3) or filtered pollutant-free air for up to 72 h. CBB-stained gels revealed changes in ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) protein. By Western analysis changes in marker proteins for O(3) damage in leaves by 1-DE were checked. In bean leaves, two superoxide dismutase (SOD) protein (19 and 20 kDa) were dramatically decreased, while ascorbate peroxidase (APX, 25 kDa), small heat shock protein (HSP, 33 kDa), and a naringenin-7-O-methyltransferase (NOMT, 42 kDa) were increased by O(3). In maize leaves, expression levels of catalase (increased), SOD (decreased), and APX (increased) were drastically changed by O(3) depending on the leaf stage, whereas crossreacting HSPs (24 and 30 kDa) and NOMT (41 kDa) proteins were strongly increased in O(3)-stressed younger leaves. These results indicated a clear modulation of oxidative stress-, heat shock-, and secondary metabolism-related proteins by O(3). Finally, 2-DE at 72 h after O(3) exposure revealed changes (induction/suppression) in expression levels of 25 and 12 protein spots in bean and maize leaves, respectively. Out of these, ten and nine nonredundant proteins in bean and maize, respectively, were identified by MS. A novel pathogenesis-related protein 2 may serve as a potential marker for O(3) stress in bean.


AIDS fatigue and university students' talk about HIV risk.
Drawing on a qualitative study that included 20 focus group discussions with male and female students at an urban-based university in South Africa, this article reports on perceptions, attitudes and reported behaviour with respect to HIV and AIDS and safer sex in the campus setting, with an aim to better understand how young people are responding to the challenges of HIV and AIDS in contemporary South Africa. The findings demonstrate the gap between reported HIV-prevention knowledge and safer-sex practices among a group of young and educated South Africans. Although the participants reported that students were knowledgeable about HIV and had easy access to condoms on campus, a range of factors mediated their capacity to apply this knowledge to safer-sex practices. Besides the usual set of complex social-cultural dynamics, including normative gender roles and power inequalities between men and women, socioeconomic challenges, and differences in age and status between sexual partners, the findings reveal substantial denial, stigma and HIV/AIDS 'fatigue.' The findings point to the importance of seeking creative ways to impart HIV-prevention and safer-sex messages that are not explicitly referent to HIV but link rather with broader issues concerning relationships, lifestyle and identity, and hence are responsive to the particular cultural context of university campuses.


TRAIL inhibits tumor growth but is nontoxic to human hepatocytes in chimeric mice.
Tumor necrosis factor (TNF) family ligand TNF-alpha and Fas ligand (FasL) can trigger apoptosis in solid tumors, but their clinical usage has been limited by hepatotoxicity. TNF-related apoptosis-inducing ligand (TRAIL) is a newly identified member of the TNF family, and its clinical application currently is under a similar debate. Here, we report a recombinant soluble form of human TRAIL (114 to 281 amino acids) that induces apoptosis in tumor cells but not human hepatocytes. We first isolated human hepatocytes from patients and showed that the human hepatocytes expressed Fas but no TRAIL death receptor DR4 and little DR5 on the cell surface. Antibody cross-linked FasL, but not TRAIL, triggered apoptosis of the human hepatocytes through cleavage of caspases. We then examined TRAIL hepatotoxicity in severe combined immunodeficient/Alb-uPA chimeric mice harboring human hepatocytes. Intravenous injection of FasL, but not TRAIL, caused apoptotic death of human hepatocytes within the chimeric liver, thus killing the mice. Finally, we showed that repeated intraperitoneal injections of TRAIL inhibited intraperitoneal and subcutaneous tumor growth without inducing apoptosis in human hepatocytes in these chimeric mice. The results indicate that the recombinant soluble human TRAIL has a profound apoptotic effect on tumor cells but is nontoxic to human hepatocytes in vitro and in vivo.


Interocular transfer in goldfish: color easier than pattern.
Goldfish were trained to monocularly discriminate different patterns that also differed in color. When tested with reversed combinations of color and pattern cues, the fish responded on the basis of pattern while using the trained eye but on the basis of color while using the untrained eye. Interhemispheric transfer of color information was therefore more effective than that of pattern.


Why medical professionals have no moral claim to conscientious objection accommodation in liberal democracies.
We describe a number of conscientious objection cases in a liberal Western democracy. These cases strongly suggest that the typical conscientious objector does not object to unreasonable, controversial professional services-involving torture, for instance-but to the provision of professional services that are both uncontroversially legal and that patients are entitled to receive. We analyse the conflict between these patients' access rights and the conscientious objection accommodation demanded by monopoly providers of such healthcare services. It is implausible that professionals who voluntarily join a profession should be endowed with a legal claim not to provide services that are within the scope of the profession's practice and that society expects them to provide. We discuss common counterarguments to this view and reject all of them.


Internalization and recycling of glycoprotein 280 in BN/MSV yolk sac epithelial cells: a model system of relevance to receptor-mediated endocytosis in the renal proximal tubule.
The processes of endocytosis and recycling have been well characterized in renal proximal tubule and yolk sac epithelia. We utilized a yolk sac teratocarcinoma cell line, BN/MSV, which expresses two glycoproteins, megalin/gp330 and gp280, also detected in renal proximal tubule and yolk sac epithelial cells. In this study, we further define the localization, internalization and intracellular trafficking of both proteins in BN/MSV cells. For this purpose, double indirect immunofluorescence and immunoelectron microscopy were performed on BN/MSV cells. In addition, antibodies against gp280 and gp330, coupled to colloidal gold particles, were used as tracers to follow the endocytosis and recycling of the two glycoproteins in BN/MSV cells. BSA and MOPC21 (a nonspecific monoclonal antibody) coupled to gold particles were used as controls. We have previously shown that gp280 and megalin/gp330 were localized in clathrin-coated pits; both proteins can also be detected in noncoated areas. Vesicular labeling has previously been seen in the cytoplasm of permeabilized BN/ MSV cells. The results of the present study revealed that the glycoproteins were colocalized in the same cells. Ultrastructural analysis of ultracryosections of BN/MSV cells revealed a localization of both proteins in coated invaginations and small and large endocytic vacuoles. In addition, gp280 and megalin/gp330 were found in the Golgi apparatus and in the granular endoplasmic reticulum. Furthermore, incubation of BN/MSV cells in the presence of colloidal gold particles labeled with antibodies to gp280 and gp330 demonstrated an internalization from the apical membrane through coated pits into small and large endocytic vacuoles. While anti-gp330 is predominantly localized in large endocytic vacuoles, the anti-gp280 gold is mainly concentrated in the tubulovesicular structures, which probably correspond to dense tubules known to enable membrane recycling in the epithelial cells of renal proximal tubules. Moreover, anti-gp330 gold particles are also found in lysosomes, but to a lesser extent than BSA and MOPC21 gold particles, which were highly concentrated in lysosomes. In conclusion, our results show that gp280 is internalized in BN/MSV cells and that anti-gp280 gold is accumulated in a recycling compartment. Thus, we suggest that gp280 is a receptor for endocytosis.


Applied medical informatics and computing skills of students, residents, and faculty.
Little is known regarding the applied medical informatics and computing skills of family practice residents and faculty, yet such information is critical when planning a medical informatics curriculum. We conducted a survey at our institution to collect this information. An applied medical informatics and computing skills survey was administered to 93 first-year medical students, 42 family practice residents, and 14 family medicine faculty. Responses were compared between groups before and after stratification by age and gender. A total of 92% of students, 100% of residents, and 79% of faculty responded. Faculty had the highest rate of computer ownership (91%), followed by students (86%) and family practice residents (79%). Students and interns had the highest overall confidence using computers, followed by faculty and then senior residents. Faculty, students, and junior residents were significantly more confident than senior residents in their ability to perform several specific tasks, such as conducting a MEDLINE search. Residents perceived lack of money and time as barriers to improving their skills. Current senior residents may require remedial training to graduate with the computer skills specified in curricular guidelines. While upcoming medical students and interns will demand more advanced training, faculty may not have the skills to provide it.


Regulation of capacitative and non-capacitative Ca2+ entry in A7r5 vascular smooth muscle cells.
A capacitative Ca2+ entry (CCE) pathway, activated by depletion of intracellular Ca2+ stores, is thought to mediate much of the Ca2+ entry evoked by receptors that stimulate phospholipase C (PLC). However, in A7r5 vascular smooth muscle cells, vasopressin, which stimulates PLC, empties intracellular Ca2+ stores but simultaneously inhibits their ability to activate CCE. The diacylglycerol produced with the IP3 that empties the stores is metabolized to arachidonic and this leads to activation of nitric oxide (NO) synthase, production of NO and cyclic GMP, and consequent activation of protein kinase G. The latter inhibits CCE. In parallel, NO directly activates a non-capacitative Ca2+ entry (NCCE) pathway, which is entirely responsible for the Ca2+ entry that occurs in the presence of vasopressin. This reciprocal regulation of two Ca2+ entry pathways ensures that there is sequential activation of first NCCE in the presence of vasopressin, and then a transient activation of CCE when vasopressin is removed. We suggest that the two routes for Ca2+ entry may selectively direct Ca2+ to processes that mediate activation and then recovery of the cell.


[New non-steroidal anti-inflammatory drugs (NSAID's) with lesser side effects, and over-the-counter low-dose preparations].
Three recent developments with respect to therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) are the identification of two isoenzymes of cyclooxygenase (COX-1 and COX-2), the development of NO-NSAIDs, and the availability of low-dose over-the-counter (OTC) NSAIDs. COX-1 products mainly have a physiologically regulating and protective effect, while COX-2 products result in inflammation. There is initial enthousiasm for selective COX-2 antagonists with respect to the gastrointestinal adverse reactions. However, recent animal data indicate that high doses of COX-2 antagonists are usually necessary to obtain an adequate anti-inflammatory effect, which doses also antagonize COX-1. The development of NO-NSAIDs is also promising. These drugs release NO which may protect the local microvasculature. However, there is as yet hardly any practical experience with these drugs. OTC use of low-dose NSAIDs is increasing. As far as is now known, the overall risk is low because of the lower dose used. Nevertheless, the usual contra-indications should be kept in mind, such as age over 60 years, a prior history of peptic ulcers, co-morbidity, and concurrent treatment with other NSAIDs or anticoagulants.


Safety and long-term immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in adults in Sierra Leone: a combined open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2 trial.
The Ebola epidemics in west Africa and the Democratic Republic of the Congo highlight an urgent need for safe and effective vaccines to prevent Ebola virus disease. We aimed to assess the safety and long-term immunogenicity of a two-dose heterologous vaccine regimen, comprising the adenovirus type 26 vector-based vaccine encoding the Ebola virus glycoprotein (Ad26.ZEBOV) and the modified vaccinia Ankara vector-based vaccine, encoding glycoproteins from Ebola virus, Sudan virus, and Marburg virus, and the nucleoprotein from the Tai Forest virus (MVA-BN-Filo), in Sierra Leone, a country previously affected by Ebola. The trial comprised two stages: an open-label, non-randomised stage 1, and a randomised, double-blind, controlled stage 2. The study was done at three clinics in Kambia district, Sierra Leone. In stage 1, healthy adults (aged ≥18 years) residing in or near Kambia district, received an intramuscular injection of Ad26.ZEBOV (5 × 1010 viral particles) on day 1 (first dose) followed by an intramuscular injection of MVA-BN-Filo (1 × 108 infectious units) on day 57 (second dose). An Ad26.ZEBOV booster vaccination was offered at 2 years after the first dose to stage 1 participants. The eligibility criteria for adult participants in stage 2 were consistent with stage 1 eligibility criteria. Stage 2 participants were randomly assigned (3:1), by computer-generated block randomisation (block size of eight) via an interactive web-response system, to receive either the Ebola vaccine regimen (Ad26.ZEBOV followed by MVA-BN-Filo) or an intramuscular injection of a single dose of meningococcal quadrivalent (serogroups A, C, W135, and Y) conjugate vaccine (MenACWY; first dose) followed by placebo on day 57 (second dose; control group). Study team personnel, except those with primary responsibility for study vaccine preparation, and participants were masked to study vaccine allocation. The primary outcome was the safety of the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen, which was assessed in all participants who had received at least one dose of study vaccine. Safety was assessed as solicited local and systemic adverse events occurring in the first 7 days after each vaccination, unsolicited adverse events occurring in the first 28 days after each vaccination, and serious adverse events or immediate reportable events occurring up to each participant's last study visit. Secondary outcomes were to assess Ebola virus glycoprotein-specific binding antibody responses at 21 days after the second vaccine in a per-protocol set of participants (ie, those who had received both vaccinations within the protocol-defined time window, had at least one evaluable post-vaccination sample, and had no major protocol deviations that could have influenced the immune response) and to assess the safety and tolerability of the Ad26.ZEBOV booster vaccination in stage 1 participants who had received the booster dose. This study is registered at ClinicalTrials.gov, NCT02509494. Between Sept 30, 2015, and Oct 19, 2016, 443 participants (43 in stage 1 and 400 in stage 2) were enrolled; 341 participants assigned to receive the Ad26.ZEBOV and MVA-BN-Filo regimen and 102 participants assigned to receive the MenACWY and placebo regimen received at least one dose of study vaccine. Both regimens were well tolerated with no safety concerns. In stage 1, solicited local adverse events (mostly mild or moderate injection-site pain) were reported in 12 (28%) of 43 participants after Ad26.ZEBOV vaccination and in six (14%) participants after MVA-BN-Filo vaccination. In stage 2, solicited local adverse events were reported in 51 (17%) of 298 participants after Ad26.ZEBOV vaccination, in 58 (24%) of 246 after MVA-BN-Filo vaccination, in 17 (17%) of 102 after MenACWY vaccination, and in eight (9%) of 86 after placebo injection. In stage 1, solicited systemic adverse events were reported in 18 (42%) of 43 participants after Ad26.ZEBOV vaccination and in 17 (40%) after MVA-BN-Filo vaccination. In stage 2, solicited systemic adverse events were reported in 161 (54%) of 298 participants after Ad26.ZEBOV vaccination, in 107 (43%) of 246 after MVA-BN-Filo vaccination, in 51 (50%) of 102 after MenACWY vaccination, and in 39 (45%) of 86 after placebo injection. Solicited systemic adverse events in both stage 1 and 2 participants included mostly mild or moderate headache, myalgia, fatigue, and arthralgia. The most frequent unsolicited adverse event after the first dose was headache in stage 1 and malaria in stage 2. Malaria was the most frequent unsolicited adverse event after the second dose in both stage 1 and 2. No serious adverse event was considered related to the study vaccine, and no immediate reportable events were observed. In stage 1, the safety profile after the booster vaccination was not notably different to that observed after the first dose. Vaccine-induced humoral immune responses were observed in 41 (98%) of 42 stage 1 participants (geometric mean binding antibody concentration 4784 ELISA units [EU]/mL [95% CI 3736-6125]) and in 176 (98%) of 179 stage 2 participants (3810 EU/mL [3312-4383]) at 21 days after the second vaccination. The Ad26.ZEBOV and MVA-BN-Filo vaccine regimen was well tolerated and immunogenic, with persistent humoral immune responses. These data support the use of this vaccine regimen for Ebola virus disease prophylaxis in adults. Innovative Medicines Initiative 2 Joint Undertaking and Janssen Vaccines & Prevention BV.


Evaluation of collagen modification and surface properties of a bovine artery via polyepoxy compound fixation.
Collagen of bovine internal thoracic artery (BITA) was treated with glutaraldehyde (GA) or polyepoxy compounds (PC). This study was to evaluate the surface properties as a result of tissue tanning reaction with PC. The fixation resulted in a significant reduction of available lysine, histidine, and other amino acid residues in PC fixed grafts as compared to fresh pre-fixed arteries. Among them, the lysine (Lys) content was reduced by about 80%, indicating that PC reactions mainly involve with Lys residues. Both PC and GA treatment led to crosslinking as evidenced by the increase in the denaturation temperature. The critical surface tension and the Fourier Transform Infrared Spectrum (FTIR) on a pre-implant and its 96 days explant were evaluated and found to be similar. The FTIR analysis of a pre-implant and the 96 day explant indicated that there was no lipid deposition.


Perchlorate detection via an invertebrate biosensor.
Improvised explosive devices (IEDs) are constructed from easily obtainable ingredients that are often unregulated and difficult to trace. Salts of the oxyhalide perchlorate are frequently used as oxidisers in IEDs and in commercially available munitions, thus a reliable detection is needed to aid forensic investigations and the tracing of environmental ground or surface water contamination. We introduce the nematode Caenorhabditis elegans as a biosensor for the presence of perchlorate, a promising alternative to the costly, technically challenging and time-consuming current perchlorate detection methods. Perchlorate uptake dynamics in C. elegans were first validated using ion exchange chromatography followed by assessing the effects of perchlorate on key life-point indices to verify the suitability of the nematodes as a forensic biosensor. Whole genome microarrays and qPCR analyses established that a set of immune and stress response genes were enriched during perchlorate exposure. A nematode strain (agIs219) containing an integrated copy of the significantly overexpressed t24b8.5 gene promoter followed by a GFP reporter gene was shown to fluoresce in a perchlorate dose dependent manner with a limit of detection (LOD) of 0.5 mg mL-1. Whilst chemicals commonly used in the construction of IEDs did not induce fluorescence, exposure to other oxyhalides did, highlighting the presence of possible shared stress response pathways. Burnt wire sparklers containing potassium perchlorate elicited fluorescence while other non-perchlorate containing post-blast explosion matrices did not. This demonstrates how C. elegans can be used to screen for perchlorate at environmental hotspots, an optimization, possibly with other target transgenes, is required to enable the detection of perchlorate at concentrations below 0.5 mg mL-1.


Retrograde jugular flow associated with idiopathic normal pressure hydrocephalus.
To clarify the relation between the drainage pathway of cerebrospinal fluid and the development of idiopathic normal pressure hydrocephalus (iNPH), we examined flow patterns of internal jugular veins in 20 patients with iNPH and 13 control patients using air-contrast ultrasound venography during the Valsalva maneuver. The iNPH group had a significantly greater frequency of retrograde jugular venous flow (19/20, 95%) than the control group (3/13, 23%) (chi(2) test, p < 0.001). Our results suggest that retrograde jugular venous flow may be associated with the development of iNPH; therefore, the analysis of retrograde jugular venous flow could be a useful element in the diagnosis of iNPH.


Attitudes on Equal Health Care Access versus Efficient Clinical Decisions across a Not-for-Profit Health Care System.
Professional roles within a hospital system may influence attitudes behind clinical decisions. To determine participants' preferences about clinical decisions that either value equal health care access or efficiency. Deidentified survey asking participants to choose between offering a low-cost screening test to a whole population ("equal access") or a more sensitive, expensive test that could be given to only half of the population but resulting in 10% more avoided deaths ("efficient"). Data collection took place from August 18, 2021, to January 24, 2022. Study 1644 was determined to be exempt by Tufts Health Sciences Institutional Review Board (IRB). Tufts Medicine Healthcare System. Approximately 15,000 hospital employees received an e-mail from the Tufts Medicine Senior Vice President of Academic Integration. Analysis of survey responses with chi-square and 1-sample t tests to determine the proportion who chose each option. Logistic regression models fit to examine relationships between professional role and test choice. A total of 1,346 participants completed the survey (∼9.0% response rate). Overall, approximately equal percentages of respondents chose the "equal access" (48%) and "efficient" option (52%). However, gender, professional role (categorical), and clinical role (dichotomous) were significantly associated with test choice. For example, among those in nonclinical roles, women were more likely than men to choose equal health care access. In multivariable analyses, having clinical roles was significantly associated with 1.73 times the likelihood of choosing equal access (95% confidence interval = 1.33-2.25). Generalizability concerns and survey question wording limit the study results. Clinicians were more likely than nonclinicians to choose the equal health care access option, and health care administrators were more likely to choose efficiency. These differing attitudes can affect patient care and health care quality. Divergent preferences of valuing equal health care access and efficiency may be in conflict during clinical decision making.In this cross-sectional study that included 1,346 participants, approximately equal percentages of respondents chose the "equal access" (48%) and "efficient" option (52%), a nonsignificant difference. However, gender, professional role (categorical), and clinical role (dichotomous) were significantly associated with test choiceSince clinicians were more likely than nonclinicians to choose the equal health care access option and health care administrators were more likely to choose efficiency, these differing attitudes can affect patient care and health care quality.


The use of saralasin in the recognition of angiotensinogenic hypertension.
Specific antagonists of angiotensin II (AII) such as saralasin might theoretically be of great value in the recognition of angiotensinogenic hypertension. Evidence is presented to show the importance of overcoming any existing sodium overload and of administering saralasin first in small and then in larger amounts by infusion (or injection). When this was done in 600 hypertensive patients, 62 showed a fall in blood pressure of more than 10/8 mm Hg. Further tests in 50 of these subjects indicated that the fall in blood pressure was associated with high peripheral levels of plasma renin activity (PRA) and/or abnormal renal vein PRA ratios in 94%. The procedure rarely failed to detect even mild forms of angiotensinogenic hypertension. In 62 patients found to have angiotensinogenic hypertension, the responsible lesions included unilateral renal arterial stenosis with good contralateral renal function (29%), bilateral renal disease (21%), Cushing's syndrome (6%), small vessel disease or specific excess of renin production - without other detectable renal disease - (31%) and incompletely evaluated disorders (13%). Saralasin has been of great value in simply and reliably demonstrating the presence or absence of an angiotensinogenic component in a large group of hypertensive patients.


Fire cues trigger germination and stimulate seedling growth of grass species from Brazilian savannas.
Although fire cues (high temperatures and smoke) influence seed germination in numerous species from fire-prone environments, their effects on seed germination of species from neotropical savannas are poorly understood. We exposed seeds of eight grass species from the Cerrado, the Brazilian savanna to heat-shock (80°C or 110°C for 5 min) and/or smoke water, and then set them to germinate in light or dark, at either summer (28°C/18°C) or winter (27°C/14°C) temperature regimes in an incubator. In addition, we evaluated the effects of smoke water on seedling root and shoot growth for four of the species. Smoke interacted with the dark treatment to increase germination from 28% to 93% in Aristida recurvata and 77% to 95% in Aristida riparia. Smoke had no effect on germination of either of these species in the light. Heat-shock alone also promoted seed germination in A. recurvata. For Digitaria lehmanniana, smoke interacted with heat-shock to improve germination from 5% to 16%. In contrast, the fire treatments did not have any effect on the seed germination of the remaining five species. Smoke water stimulated root growth for A. riparia, A. recurvata, and Ctenium cirrosum but had no effect on their shoot growth. The strong promotive effect of smoke on Aristida germination suggests that these species are fire-adapted. Aristida species have an active awn system, which facilitates seed burial, and the smoke and dark interaction would ensure buried seeds germinated post-fire. The species that showed no response to fire cues may either have adapted via alternative strategies or require different concentrations of smoke or levels of heat. This study is one of very few examples showing a positive germination and seedling growth response to smoke for species from neotropical savannas.


Optical and acoustical observations of the effects of ultrasound on contrast agents.
Optimal use of encapsulated microbubbles for ultrasound contrast agents and drug delivery requires an understanding of the complex set of phenomena that affect the contrast agent echo and persistence. With the use of a video microscopy system coupled to either an ultrasound flow phantom or a chamber for insonifying stationary bubbles, we show that ultrasound has significant effects on encapsulated microbubbles. In vitro studies show that a train of ultrasound pulses can alter the structure of an albumin-shelled bubble, initiate various mechanisms of bubble destruction or produce aggregation that changes the echo spectrum. In this analysis, changes observed optically are compared with those observed acoustically for both albumin and lipid-shelled agents. We show that, when insonified with a narrowband pulse at an acoustic pressure of several hundred kPa, a phospholipid-shelled bubble can undergo net radius fluctuations of at least 15%; and an albumin-shelled bubble initially demonstrates constrained expansion and contraction. If the albumin shell contains air, the shell may not initially experience surface tension; therefore, the echo changes more significantly with repeated pulsing. A set of observations of contrast agent destruction is presented, which includes the slow diffusion of gas through the shell and formation of a shell defect followed by rapid diffusion of gas into the surrounding liquid. These observations demonstrate that the low-solubility gas used in these agents can persist for several hundred milliseconds in solution. With the transmission of a high-pulse repetition rate and a low pressure, the echoes from, contrast agents can be affected by secondary radiation force. Secondary radiation force is an attractive force for these experimental conditions, creating aggregates with distinct echo characteristics and extended persistence. The scattered echo from an aggregate is several times stronger and more narrowband than echoes from individual bubbles.


[Intensification of cellular immune response by immunization of mice with the cells preincubated in interferon].
Mice F1(CBA X C57BL/6) were immunized intraperitoneally with a single injection of L-1210 cells preincubated in interferon or control "false" preparation. CBA mice were injected with MX-11 cells: similarly treated according to the same scheme. Injection of interferon-treated cells was accompanied by the enhancement of the cellular immune response. The greatest cytotoxic activity was possessed by the lymphocytes of mice to which M-11 cells were administered together with interferon in which the cells were formerly incubated.


Effects of acute alcohol consumption and alcohol expectancy on processing of perceptual cues of emotional expression.
We recently demonstrated that alcohol elicits a difference between men and women in perceptual threshold for facial expressions of sadness. However, this study did not include a manipulation of alcohol expectancy. Therefore, we sought to determine whether these effects may be due to the expectation of having consumed alcohol. Male and female participants (n = 100) were randomised using a balanced-placebo design to receive either an alcoholic or a non-alcoholic drink and to be told that this was alcoholic or non-alcoholic. Participants completed a psychophysical task which presented male and female faces expressing angry, happy, and sad emotions. Analysis of threshold data indicated a significant two-way interaction of drink x target emotion, reflecting a higher threshold for the detection of sad facial expressions of emotion, compared with angry or happy expressions, in the alcohol condition compared with the placebo condition. We did not observe any evidence of sex differences in these effects. Our data indicate that alcohol modifies the perceptual threshold for facial expressions of sadness. Unlike our previous report, we did not observe evidence of sex differences in these effects. Most importantly, we did not observe any evidence that these effects were due to expectancy effects associated with alcohol consumption.


The anecdotal antidotes.
The author reviews obscure or unusual antidote recommendations, emphasizing antidotes or antidote uses that are not generally acknowledged or that have little experimental or clinical confirmation of their efficacy. Also included are unusual uses of well known antidotes. Among the antidotes considered are naloxone, physostigmine, folate, Prussian blue, n-acetylcysteine, cimetidine, subcutaneous magnesium salts, nicotinamide, and thioctic acid.


Hydroxyl Group Acetylation of Quercetin Enhances Intracellular Absorption and Persistence to Upregulate Anticancer Activity in HepG2 Cells.
Quercetin, a flavonoid compound widely distributed in many plants, is known to have potent antitumor effects on several cancer cells. Our previous study revealed that the acetylation of quercetin enhanced its antitumor effect. However, the mechanisms remain unknown. This study aimed to elucidate the bioavailability of acylated quercetin in the HepG2 cell model based on its antitumor effect. The positions of quercetin 3,7,3',4'-OH were acetylated as 3,7,3',4'-O-tetraacetylquercetin (4Ac-Q). The inhibitory effect of 4Ac-Q on HepG2 cell proliferation was assessed by measuring cell viability. The apoptosis was characterized by apoptotic proteins and mitochondrial membrane potential shifts, as well as mitochondrial reactive oxygen species (ROS) levels. The bioavailability of 4Ac-Q was analyzed by measuring the uptake and metabolites in HepG2 cells with high performance liquid chromatography (HPLC)-photodiode array detector (PDA) and-ultraviolet/visible detector (UV/Vis). The results revealed that 4Ac-Q enhanced the inhibitory effect on HepG2 cell proliferation and induced its apoptosis significantly higher than quercetin. Protein array analysis of apoptosis-related protein indicated that 4Ac-Q increased the activation or expression of pro-apoptotic proteins, including caspase-3, -9, as well as second mitochondria-derived activator of caspases (SMAC), and suppressed the expression of apoptosis inhibiting proteins such as cellular inhibitor of apoptosis (cIAP)-1, -2, Livin, Survivin, and X-linked inhibitor of apoptosis (XIAP). Furthermore, 4Ac-Q stimulated mitochondrial cytochrome c release into the cytosol by enhancing ROS level and depolarizing the mitochondrial membrane. Finally, the analysis of uptake and metabolites of 4Ac-Q in HpG2 cells with HPLC-PDA and -UV/Vis revealed that 4Ac-Q was metabolized to quercetin and several different acetylated quercetins which caused 2.5-fold higher quercetin present in HepG2 cells than parent quercetin. These data demonstrated that acetylation of the quercetin hydroxyl group significantly increased its intracellular absorption. Taken together, our findings provide the first evidence that acetyl modification of quercetin not only substantially augments the intracellular absorption of quercetin but also bolsters its metabolic stability to elongate its intracellular persistence. Therefore, acetylation could serve as a strategic approach to enhance the ability of quercetin and analogous flavonoids to suppress cancer cell proliferation.


Characterization of Sleeping Beauty transposition and its application to genetic screening in mice.
The use of mutant mice plays a pivotal role in determining the function of genes, and the recently reported germ line transposition of the Sleeping Beauty (SB) transposon would provide a novel system to facilitate this approach. In this study, we characterized SB transposition in the mouse germ line and assessed its potential for generating mutant mice. Transposition sites not only were clustered within 3 Mb near the donor site but also were widely distributed outside this cluster, indicating that the SB transposon can be utilized for both region-specific and genome-wide mutagenesis. The complexity of transposition sites in the germ line was high enough for large-scale generation of mutant mice. Based on these initial results, we conducted germ line mutagenesis by using a gene trap scheme, and the use of a green fluorescent protein reporter made it possible to select for mutant mice rapidly and noninvasively. Interestingly, mice with mutations in the same gene, each with a different insertion site, were obtained by local transposition events, demonstrating the feasibility of the SB transposon system for region-specific mutagenesis. Our results indicate that the SB transposon system has unique features that complement other mutagenesis approaches.


Bacterial and polymorphonuclear leukocyte contribution to middle ear inflammation in chronic otitis media with effusion.
Bacteria can be cultured from approximately one third of chronic middle ear effusions, yet the contribution of these bacteria to the pathogenesis of chronic otitis media with effusion (OME) is not clear due to the absence of signs and symptoms of acute infection in most children with this disease. To explore the role of bacteria in chronic OME, lysozyme, lactoferrin, serum complement factors C3 and C5a, and polymorphonuclear leukocyte (PMNL) chemotaxin content was measured in 21 chronic middle ear effusion samples. Concentrations of lysozyme, lactoferrin, and chemotaxin were significantly higher in culture-positive than in sterile effusions. Lysozyme appeared to be contributed by both PMNL and non-PMNL sources in the middle ear space. These non-PMNL sources, presumably middle ear epithelial cells, accounted for 50% to 80% of the lysozyme variation in middle ear effusion. Although C3 and C5a were present in effusion, chemotaxin content correlated poorly with the C3 and C5a content, suggesting that chemotaxins were derived from bacterial peptides rather than from complement activation products. These results suggest that bacteria contribute to chronic middle ear inflammation with effusion. The eradication of bacteria from chronic middle ear effusion might disrupt the host responses which maintain chronic OME.


Revisiting the codon adaptation index from a whole-genome perspective: analyzing the relationship between gene expression and codon occurrence in yeast using a variety of models.
Highly expressed genes in many bacteria and small eukaryotes often have a strong compositional bias, in terms of codon usage. Two widely used numerical indices, the codon adaptation index (CAI) and the codon usage, use this bias to predict the expression level of genes. When these indices were first introduced, they were based on fairly simple assumptions about which genes are most highly expressed: the CAI was originally based on the codon composition of a set of only 24 highly expressed genes, and the codon usage on assumptions about which functional classes of genes are highly expressed in fast-growing bacteria. Given the recent advent of genome-wide expression data, we should be able to improve on these assumptions. Here, we measure, in yeast, the degree to which consideration of the current genome-wide expression data sets improves the performance of both numerical indices. Indeed, we find that by changing the parameterization of each model its correlation with actual expression levels can be somewhat improved, although both indices are fairly insensitive to the exact way they are parameterized. This insensitivity indicates a consistent codon bias amongst highly expressed genes. We also attempt direct linear regression of codon composition against genome-wide expression levels (and protein abundance data). This has some similarity with the CAI formalism and yields an alternative model for the prediction of expression levels based on the coding sequences of genes. More information is available at http://bioinfo.mbb.yale.edu/expression/codons.


Self-association of herpes simplex virus type 1 ICP35 is via coiled-coil interactions and promotes stable interaction with the major capsid protein.
The ordered copolymerization of viral proteins to form the herpes simplex virus (HSV) capsid occurs within the nucleus of the infected cell and is a complex process involving the products of at least six viral genes. In common with capsid assembly in double-stranded DNA bacteriophages, HSV capsid assembly proceeds via the assembly of an outer capsid shell around an interior scaffold. This capsid intermediate matures through loss of the scaffold and packaging of the viral genomic DNA. The interior of the HSV capsid intermediate contains the viral protease and assembly protein which compose the scaffold. Proteolytic processing of these proteins is essential for and accompanies capsid maturation. The assembly protein (ICP35) is the primary component of the scaffold, and previous studies have demonstrated it to be capable of intermolecular association with itself and with the major capsid protein, VP5. We have defined structural elements within ICP35 which are responsible for intermolecular self-association and for interaction with VP5. Yeast (Saccharomyces cerevisiae) two-hybrid assays and far-Western studies with purified recombinant ICP35 mapped a core self-association domain between Ser165 and His219. Site-directed mutations in this domain implicate a putative coiled coil in ICP35 self-association. This coiled-coil motif is highly conserved within the assembly proteins of other alpha herpesviruses. In the two-hybrid assay the core self-association domain was sufficient to mediate stable self-association only in the presence of additional structural elements in either N- or C-terminal flanking regions. These regions also contain conserved sequences which exhibit a high propensity for alpha helicity and may contribute to self-association by forming additional short coiled coils. Our data supports a model in which ICP35 molecules have an extended conformation and associate in parallel orientation through homomeric coiled-coil interactions. In additional two-hybrid experiments we evaluated ICP35 mutants for association with VP5. We discovered that in addition to the C-terminal 25 amino acids of ICP35, previously shown to be required for VP5 binding, an additional upstream region was required. This region is between Ser165 and His234 and contains the core self-association domain. Site-directed mutations and construction of chimeric molecules in which the self-association domain of ICP35 was replaced by the GCN4 leucine zipper indicated that this region contributes to VP5 binding through mediating self-association of ICP35 and not through direct binding interactions. Our results suggest that self-association of ICP35 strongly promotes stable association with VP5 in vivo and are consistent with capsid formation proceeding via formation of stable subassemblies of ICP35 and VP5 which subsequently assemble into capsid intermediates in the nucleus.


[The role of membrane phospholipids in oxidative phosphorylation. A hypothesis of LC-coupling].
The role of lipid (pentadienyl) radicals and Mitchell's "C-elements" was analyzed. The function of the "C-elements" is necessary, but not enough for coupling of oxidation and phosphorylation. It was proposed that oxidative phosphorylation in the mitochondria membrane is the result of a direct coupling, involving participation of the "LC-elements" (where L and C reflect the inductive and capacitive character of the transformation device). The "L-elements" (the short pi-system) are lipid (pentadienyl) radicals formed in polyunsaturated fatty acids of phospholipids.


Policy interventions implemented through sporting organisations for promoting healthy behaviour change.
Sporting organisations provide an important setting for health promotion strategies that involve policies, communication of healthy messages and creation of health promoting environments. The introduction of policy interventions within sporting organisations is one strategy to target high risk behaviours such as smoking, alcohol consumption, excess sun exposure, unhealthy eating and discrimination. To review all controlled evaluation studies of policy interventions organised through sporting settings to increase healthy behaviour (related to smoking, alcohol, healthy eating, sun protection, discrimination, safety and access). We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsyclNFO, CINAHL, SPORTDiscus, Sociological Abstracts, Dissertation Abstracts, freely available online health promotion and sports-related databases hosted by leading agencies, and the internet using sport and policy-related key words. We identified further studies in the bibliographies of articles and by contacting authors of key articles in the area. We aimed to identify research that had used study designs that incorporated an evaluated intervention and comparison. Uncontrolled studies, meeting other inclusion criteria, were to be reported in an annex to the review. Types of studies: Studies in which sporting organisations were allocated to a policy intervention or control/comparison group. No minimum follow-up required. People of all ages. Types of interventions: Any policy intervention implemented through sporting organisations to instigate and/or sustain healthy behaviour change, intention to change behaviour, or changes in attitudes, knowledge or awareness of healthy behaviour. Policies must address any of the following: smoking, alcohol, healthy eating, sun protection, access for disadvantaged groups, physical safety (not including injuries), and social and emotional health (e.g.. anti-vilification, anti-discrimination). Types of outcome measures: Behaviour change, intention to change behaviour, change in attitudes, knowledge or awareness of healthy behaviour, and policy presence. We assessed whether identified citations were controlled evaluation studies and investigated the use of policy implemented in sporting settings. Abstracts were independently inspected by two reviewers and full papers were obtained where necessary. As no controlled evaluation studies were located, no data collection or analysis was undertaken. No uncontrolled studies meeting other inclusion criteria were identified and therefore no annex is presented. No rigorous studies were located to test the effectiveness of policy interventions organised through sporting organisations to increase healthy behaviours, attitudes, knowledge or inclusion of health oriented policies within the organisations. We were unable to find any controlled studies to guide the use of policy interventions used in sporting settings. The search process revealed a number of case studies with anecdotal reporting of outcomes. We strongly recommend that rigorous evaluation techniques are employed more commonly in this field to illuminate the impact of health promoting policy on outcomes, and the contexts and processes which are likely to be effective in reducing harmful behaviours.


Tendon-holding capacities of two newly designed implants for tendon repair: an experimental study on the flexor digitorum profundus tendon of sheep.
Two main factors determine the strength of tendon repair; the tensile strength of material and the gripping capacity of a suture configuration. Different repair techniques and suture materials were developed to increase the strength of repairs but none of techniques and suture materials seem to provide enough tensile strength with safety margins for early active mobilization. In order to overcome this problem tendon suturing implants are being developed. We designed two different suturing implants. The aim of this study was to measure tendon-holding capacities of these implants biomechanically and to compare them with frequently used suture techniques. In this study we used 64 sheep flexor digitorum profundus tendons. Four study groups were formed and each group had 16 tendons. We applied model 1 and model 2 implant to the first 2 groups and Bunnell and locking-loop techniques to the 3rd and 4th groups respectively by using 5 Ticron sutures. In 13 tendons in group 1 and 15 tendons in group 2 and in all tendons in group 3 and 4, implants and sutures pulled out of the tendon in longitudinal axis at the point of maximum load. The mean tensile strengths were the largest in group 1 and smallest in group 3. In conclusion, the new stainless steel tendon suturing implants applied from outside the tendons using steel wires enable a biomechanically stronger repair with less tendon trauma when compared to previously developed tendon repair implants and the traditional suturing techniques.


Spatial Thinking in Term and Preterm-Born Preschoolers: Relations to Parent-Child Speech and Gesture.
Spatial skills predict important life outcomes, such as mathematical achievement or entrance into Science, Technology, Engineering, and Mathematics (STEM) disciplines. Children significantly vary in their spatial performance even before they enter formal schooling. One correlate of children's spatial performance is the spatial language they produce and hear from others, such as their parents. Because the emphasis has been on spatial language, less is known about the role of hand gestures in children's spatial development. Some children are more likely to fall behind in their spatial skills than others. Children born premature (gestational age <37 weeks) constitute such a risk group. Here, we compared performance of term and preterm-born children on two non-verbal spatial tasks-mental transformation and block design. We also examined relations of children's performance on these tasks to parental spatial language and gesture input and their own production of spatial language and gesture during an independent puzzle play interaction. We found that while term and preterm-born children (n = 40) as a group did not differ in the mental transformation or block design performance, children varied widely in their performance within each group. The variability in mental transformation scores was predicted by both a subset of spatial words (what aspects of spatial information) and all spatial gestures children produced. Children's spatial language and gesture were in turn related to their parents' spatial language and gesture. Parental spatial language and gesture had an indirect relation on children's mental transformation, but not block design, scores via children's spatial language, and gesture use. Overall, results highlight the unique contributions of speech and gesture in communicating spatial information and predicting children's spatial performance.


Intergenerational Effect of Maternal Childhood Maltreatment on Next Generation's Vulnerability to Psychopathology: A Systematic Review With Meta-Analysis.
Many studies have identified the multiple negative consequences of childhood maltreatment on subsequent mental health. However, research on the intergenerational effect of maternal childhood maltreatment has not been systematically synthesized. This meta-analysis aimed to provide a quantitative estimate of the intergenerational effect of maternal childhood maltreatment on their offspring's psychopathology. Electronic databases and gray literature were searched for English-language prospective cohort studies. Two reviewers independently extracted data and assessed study quality with the Newcastle-Ottawa Scale. This review only included those studies with (1) maternal childhood maltreatment occurring prior to 18 years of age, (2) using a clear and reliable assessment for maltreatment exposure and offspring's mental health problems prior to age 18. Random-effect models were used to calculate the pooled effect size of maternal childhood maltreatment on offspring's psychopathology, and meta-regression was used to explore potential confounders. Twelve studies met eligibility criteria. Significant heterogeneity was found across selected studies. Maternal childhood maltreatment was found to have a small but significant effect on the offspring's depression and internalizing behaviors (r = .14, 95% confidence interval [.09, .19]). Two moderators were found, maternal depression and ethnicity. Maternal depression reduced the effect size of maternal maltreatment on offspring's depression and internalizing disorders. The offspring of non-Caucasian mothers who had a history of childhood maltreatment faced a higher risk of mental health problems. There was no evidence of publication bias. This review provides robust evidence to reinforce the need for policies to reduce its occurrence, as it can influence not just one but two or possibly more generations.


Anaerobic methane oxidation inducing carbonate precipitation at abiogenic methane seeps in the Tuscan archipelago (Italy).
Seepage of methane (CH4) on land and in the sea may significantly affect Earth's biogeochemical cycles. However processes of CH4 generation and consumption, both abiotic and microbial, are not always clear. We provide new geochemical and isotope data to evaluate if a recently discovered CH4 seepage from the shallow seafloor close to the Island of Elba (Tuscany) and two small islands nearby are derived from abiogenic or biogenic sources and whether carbonate encrusted vents are the result of microbial or abiotic processes. Emission of gas bubbles (predominantly CH4) from unlithified sands was observed at seven spots in an area of 100 m2 at Pomonte (Island of Elba), with a total rate of 234 ml m-2 d-1. The measured carbon isotope values of CH4 of around -18‰ (VPDB) in combination with the measured δ2H value of -120‰ (VSMOW) and the inverse correlation of δ13C-value with carbon number of hydrocarbon gases are characteristic for sites of CH4 formation through abiogenic processes, specifically abiogenic formation of CH4 via reduction of CO2 by H2. The H2 for methanogenesis likely derives from ophiolitic host rock within the Ligurian accretionary prism. The lack of hydrothermal activity allows CH4 gas to become decoupled from the stagnant aqueous phase. Hence no hyperalkaline fluid is currently released at the vent sites. Within the seep area a decrease in porewater sulphate concentrations by ca. 5 mmol/l relative to seawater and a concomitant increase in sulphide and dissolved inorganic carbon (DIC) indicate substantial activity of sulphate-dependent anaerobic oxidation of methane (AOM). In absence of any other dissimilatory pathway, the δ13C-values between -17 and -5‰ in dissolved inorganic carbon and aragonite cements suggest that the inorganic carbon is largely derived from CH4. The formation of seep carbonates is thus microbially induced via anaerobic oxidation of abiotic CH4.


Multimodal lung cancer screening using the ITALUNG biomarker panel and low dose computed tomography. Results of the ITALUNG biomarker study.
Asymptomatic high-risk subjects, randomized in the intervention arm of the ITALUNG trial (1,406 screened for lung cancer), were enrolled for the ITALUNG biomarker study (n = 1,356), in which samples of blood and sputum were analyzed for plasma DNA quantification (cut off 5 ng/ml), loss of heterozygosity and microsatellite instability. The ITALUNG biomarker panel (IBP) was considered positive if at least one of the two biomarkers included in the panel was positive. Subjects with and without lung cancer diagnosis at the end of the screening cycle with LDCT (n = 517) were evaluated. Out of 18 baseline screen detected lung cancer cases, 17 were IBP positive (94%). Repeat screen-detected lung cancer cases were 18 and 12 of them positive at baseline IBP test (66%). Interval cancer cases (2-years) and biomarker tests after a suspect Non Calcific Nodule follow-up were investigated. The single test versus multimodal screening measures of accuracy were compared in a simulation within the screened ITALUNG intervention arm, considering screen-detected and interval cancer cases. Sensitivity was 90% at baseline screening. Specificity was 71 and 61% for LDCT and IBP as baseline single test, and improved at 89% with multimodal, combined screening. The positive predictive value was 4.3% for LDCT at baseline and 10.6% for multimodal screening. Multimodal screening could improve the screening efficiency at baseline and strategies for future implementation are discussed. If IBP was used as primary screening test, the LDCT burden might decrease of about 60%.


Multiple-object input in nonlinear correlation.
Multiple-object input to the recently introduced phase-extraction correlator may cause difficulties owing to interference effects. Similar effects have been observed previously in the nonlinear joint transform correlator. It is shown theoretically and by computer simulations that these effects are seldom observable in practice, and even then they can be substantially reduced by employing a proper space-variant threshold. The implementation of this scheme by a hybrid electro-optical architecture is also explained briefly and demonstrated. The results presented permit manipulation of information (spectral phase) that was previously believed to be contaminated beyond recovery.


Evaluation of the antigen relatedness and efficacy of a single vaccination with different infectious bronchitis virus strains against a challenge with Malaysian variant and QX-like IBV strains.
The predominant infectious bronchitis virus (IBV) strains detected in chickens in Malaysia are the Malaysian variant (MV) and QX-like, which are associated with respiratory distress, nephropathy, and high mortality. On the other hand, the antigenic relatedness and efficacy of IBV vaccines against these 2 field IBV strains are not well characterized. This study aimed to determine the antigen relatedness and efficacy of different IB vaccine strains against a challenge with MV and QX-like strains. The antigen relatedness and the ability of different IB vaccine strains in conferring protection against MV and QX-like were assessed based on the clinical signs, macroscopic lesions, and ciliary activity. The MV strain IBS037A/2014 showed minor antigenic subtype differences with the vaccine virus Mass H120 and 4/91 strains but showed major antigenic subtype differences with the K2 strain. The Malaysian QX-like strain IBS130/2015 showed major antigenic subtype differences with the MV strain IBS037A/2014 and the vaccine strains except for K2. Chickens vaccinated once with Mass (H120) or with non-Mass (4/91 and K2) developed antibody responses with the highest antibody titer detected in the groups vaccinated with H120 and 4/91. The mean ciliary activities of the vaccinated chickens were between 56 to 59% and 48 to 52% in chickens challenged with IBS037A/2014 and IBS130/2015, respectively. The vaccinated and challenged birds showed mild to severe lesions in the lungs and kidneys. Despite the minor antigenic subtype differences, a single inoculation with Mass or non-Mass vaccines could not protect against the MV IBS037A/2014 and QX-like IBS130/2015.


Identification of genes encoding zinc finger motifs in the cardiovascular system.
The Zn2+-finger DNA-binding domain has been identified in several developmental control proteins, transcription factors and gene products associated with diseases, as well as in several RNA-binding proteins. We applied library screening, expressed sequence tagging (EST sequencing), Zn2+-binding assays and Northern blot hybridization, in order to characterize novel cDNA clones of the human cardiovascular system which contain Zn2+-finger motifs. An embryonic (8-10 weeks gestation) heart lambda ZAP Express cDNA library was screened with an oligonucleotide probe deduced from a consensus amino acid sequence which is highly conserved for Zn2+-finger proteins, and approximately 350 positive clones were isolated from 1 x 10(4) plaque-forming units (pfu) initially plated. The isolated clones were classified as known and novel following single pass automated DNA sequencing. Analysis of Northern blot hybridization delineated the tissue specificity of these clones, as well as their association with cardiac growth and development. Existence of Zn2+-finger motifs in the novel clones was confirmed by Zn2+-binding assay. In this report, we present the characterization of eight novel clones, including the complete cDNA sequences of one of these clones (HHZ-123).


GRB7 protein over-expression and clinical outcome in breast cancer.
The growth factor receptor-bound protein-7 gene (GRB7) encodes a multi-domain signal transduction molecule. The purpose of this study was to examine the clinical significance of GRB7 protein expression in human breast cancer. Western blotting analysis of protein extracts from 563 annotated frozen breast tumors was performed. Expression status of GRB7 and HER-2 was correlated with clinical covariates and outcomes. Cox proportional hazards were used to identify factors associated with breast cancer-free interval. The median follow-up was 71 months. P values <0.05 were considered statistically significant (two-sided). A discrepancy between HER-2 and GRB7 protein over-expression was observed. GRB7 protein over-expression was associated with negative estrogen and progesterone receptor status, higher tumor grade, larger primary tumor size, (more) axillary lymph node involvement, higher clinical stage, and shortened breast cancer-free interval. HER-2 protein over-expression was associated only with higher tumor grade. Multi-variate analysis revealed that GRB7 protein over-expression was an independent adverse prognostic factor for breast cancer-free interval (hazard ratio 1.69, 95% confidence interval 1.07-2.67; P = 0.024). The same was true of the subset of patients who did not receive any adjuvant systemic therapy (hazard ratio 1.68, 95% confidence interval 1.16-2.31; P = 0.0055). Using FISH analysis, 32/32 (100%; 95% CI 89-100%) tumors which over-expressed both HER-2 and GRB7 proteins and 1/35 (3%; 95% CI 0-15%) tumors with HER-2 but no GRB7 protein over-expression with Western blotting analysis demonstrated HER-2 gene amplification. GRB7 protein over-expression is an independent adverse prognostic factor in human breast cancer.


Influence of Microencapsulated Phase Change Material (PCM) Addition on (Micro) Mechanical Properties of Cement Paste.
Excessive cracking can be a serious durability problem for reinforced concrete structures. In recent years, addition of microencapsulated phase change materials (PCMs) to concrete has been proposed as a possible solution to crack formation related to temperature gradients. However, the addition of PCM microcapsules to cementitious materials can have some drawbacks, mainly related to strength reduction. In this work, a range of experimental techniques has been used to characterize the microcapsules and their effect on properties of composite cement pastes. On the capsule level, it was shown that they are spherical, enabling good distribution in the material during the mixing process. Force needed to break the microcapsules was shown to depend on the capsule diameter and the temperature, i.e., whether it is below or above the phase change temperature. On the cement paste level, a marked drop of compressive strength with increasing PCM inclusion level was observed. The indentation modulus has also shown to decrease, probably due to the capsules themselves, and to a lesser extent due to changes in porosity caused by their inclusion. Finally, a novel micro-cube splitting technique was used to characterize the tensile strength of the material on the micro-meter length scale. It was shown that the strength decreases with increasing PCM inclusion percentage, but this is accompanied by a decrease in measurement variability. This study will contribute to future developments of cementitious composites incorporating phase change materials for a variety of applications.


Nanomedicine for Cancer Therapy Using Autophagy: An Overview.
Autophagy is an intracellular biological catabolic process of mammalian cells to maintain the homeostasis. It plays a wide role in the clearance of damaged cellular organelles, misfolded or aggregated proteins like alpha-synuclein, β-amyloid peptides, Tau proteins and pathogens. Recent studies have clearly demonstrated that dysfunction in autophagy leads to the development of cancer, cardiomyopathy, chronic infection, neurodegenerative and other diseases. Therefore, modulation of autophagy has therapeutic value to cure the diseases including cancer using external stimuli. In this context, various researchers developed small molecules such as chloroquine, rapamycin, etc. for the treatment of cancer through autophagy. However, these molecules possess side effects which limit their use in the clinics. Therefore, nanomedicine approach could stand as an alternative treatment option to induce the autophagy in cancer therapy. Several investigators developed a variety of nanomaterials which themselves act as autophagy inducers or inhibitors. Considering this, the present review article will focus on the recent developments of nanomedicine in the area of autophagy that have been focused on the treatment of cancers. We also summarised the detailed mechanisms of nanoparticles mediated autophagy which could be helpful for developing new strategies to fight against cancer. Also, the present review article covers the current clinical status of nanomedicine and future challenges. Finally, we conclude with the future potential role of nanomedicine for autophagy induction in the cancer treatment.


Low immunoglobulin G3 levels in wheezy children.
This study aimed to investigate the prevalence of IgG subclass deficiency in wheezy children aged <3 y. Serum levels of IgA, IgE and IgG subclasses were measured in 310 children with recurrent wheezing and in 100 healthy controls. IgG3 levels were below the normal lower limit in 123 (39.6%) patients. This finding may reflect delayed maturation of the immune system, predisposing young children <3 y of age to wheezing.


Effects of impulse frequency, PTP, and temperature on responses elicited in large populations of motoneurons by impulses in single Ia-fibers.
Excitatory postsynaptic potentials (EPSPs) were evoked in large populations of motoneurons by impulses in single Ia- and group II fibers and recorded from L7 and S1 ventral roots by means of a sucrose-gap technique and spike-triggered averaging, as previously described (33, 34). Factors known to influence conduction at branch points in peripheral nerves or transmission in the Ia projection to motoneurons were studied to determine their effects on these postsynaptic population potentials (PSPPs). When impulse frequency was plotted against the amplitude of these PSPPs, a sequence of low-frequency depression, higher frequency facilitation, and still higher frequency depression was regularly observed. Similar plots of PSPP amplitude versus impulse frequency in a small sample of group II spindle fibers did not reveal any low-frequency depression. Higher frequency facilitation and depression followed the same pattern as that produced by Ia-fibers. Early potentiation of the PSPPs was produced by applying 20 stimulating pulses at 500/s to branches of the medial gastrocnemius nerves containing single Ia-fibers. Single, posttetanic PSPPs were recorded at fixed intervals following each tetanus and averaged. A brief, initial depression followed by a rapidly declining potentiation of PSPPs was regularly observed. When the core temperature was reduced from 41 to 35 degrees C, there was an approximately linear increase in the amplitude of PSPPs. At each temperature a combination of cooling and posttetanic potentiation (PTP) elicited larger PSPPs than cooling alone. The effects of impulse frequency, PTP, and temperature on PSPPs may all be interpreted in terms of their known effects on action potentials or on conduction at branch points in peripheral nerves. Similar effects on transmission or transmission failure in the terminal arborizations of Ia-fibers would account for the influence of these factors on PSPPs. Alternatively, these same three factors might cause similar effects on PSPPs through influences they might exert on the transmitter release mechanism.


[Kinetic regularities of RNA synthesis. VI. Reverse problem of RNA accumulation in synchronous cell cultures].
An algorithm is presented for determining relative nucleotide composition and rates of synthesis of some RNA fractions according to the experimental data of the change with time of mean nucleotide composition of the mixture of RNA fractions of synchroneous cell culture. Piece-linear models with voluntary number of fractures are taken as the models of accumulation of separate RNA types.


Phosphorylation of sterol regulatory element binding protein-1a by protein kinase A (PKA) regulates transcriptional activity.
The counter-regulatory hormone glucagon inhibits lipogenesis via downregulation of sterol regulatory element binding protein 1 (SREBP-1). The effect of glucagon is mediated via protein kinase A (PKA). To determine if SREBP-1 is a direct phosphorylation target of PKA, we conducted mass spectrometry analysis of recombinant n-terminal SREBP-1a following PKA treatment in vitro. This analysis identified serines 331/332 as bona-fide phosphorylation targets of PKA. To determine the functional consequences of phosphorylation at these sites, we constructed mammalian expression vector for both nSREBP-1a and 1c isoforms in which the candidate PKA phosphorylation sites were mutated to active phosphomimetic or non-phosphorylatable amino acids. The transcriptional activity of SREBP was reduced by the phosphomimetic mutation of S332 of nSREBP-1a and the corresponding serine (S308) of nSREBP-1c. This site is a strong candidate for mediating the negative regulatory effect of glucagon on SREBP-1 and lipogenesis.


[Spirometric evaluation of external respiration function in laparoscopic and mini-laparotomy cholecystectomy].
Spirometric parameters are studied in 54 patients subjected to laparoscopic cholecystectomy and cholecystectomy through a mini-laparotomy approach. The restrictive and obstructive disorders in the external respiratory function after minilaparotomy cholecystectomy are less expressed than after laparoscopic cholecystectomy. Thorough examination of the external respiratory function is recommended when defining the indications for laparoscopic cholecystectomy.


Developing a rural workforce through medical education: lessons from down under.
Rural Clinical Schools in Australia are a government initiative to help address the rural workforce shortage at the medical school level. This article reports on the approaches and outcomes from one Rural Clinical School. The program is underpinned by an 8-week rural rotation for all 3rd-year students and a yearlong program of core clinical rotations for 25% of the Year 3 cohort. Aspects of experiential, situated, service, and self-directed learning along with interprofessional study are integrated to provide unique rural-focused learning opportunities. Compared to their urban counterparts, rural students see more patients, perform a greater number of procedures, and achieve as well in exam results. Early indications suggest that our program is attracting more Year 3 students to explore the rural pathway as an option to a future career. The program demonstrates that rural students achieve as well as their urban counterparts.


Assessment of the anterior spinal artery and the artery of Adamkiewicz using multi-detector CT angiography.
Damage to the spinal cord after the treatment of the descending thoracic and thoracoabdominal aortic aneurysms is an uncommon but devastating complication. The artery of Adamkiewicz (AKA) is the principal arterial supply of the anterior spinal artery (ASA) in the lower thoracic and lumbar level. The purpose of this study was to evaluate the visualization of the anterior spinal artery and the artery of Adamkiewicz, the affecting factors for the detection rate using multi-detector row CT (MDCT). Ninety-nine consecutive patients (31 women and 68 men; age range, 25 - 90 years; average age 61.3 years), with suspicion for thoracic aortic lesions necessitating surgical intervention (31 aortic aneurysm, 45 dissection, 5 intramural hematoma, and 18 normal), underwent CT angiography from the aortic arch to the aortic bifurcation. Transverse sections, multiplanar reformations and thin maximum intensity projections were used to assess the ASA and AKA. The level of the ASA and AKA origins and CT acquisition parameters were recorded. The contrast-to-noise ratio of the image, an index of the mass of the T11 body (vertebral mass index), the subcutaneous fat thickness, and the CT value within the aortic arch and at the T11 level were measured. The detection of the ASA and AKA were evaluated relative to the acquisition parameters, scan characteristics, and aortic lesion type. Differences were assessed with the Wilcoxon rank-sum and t tests. The ASA was visualized in 51 patients (52%) and the AKA in 18 patients (18%). The ASA was identified in 36/67 patients (54%) with 1.25 mm thickness and in 15/32 patients (47%) with 2.5 - 3.0 mm thickness. This difference did not achieve significance (P = 0.13). The detection rate of the ASA and the AKA was influenced by the vertebral mass index and the contrast-to-noise ratio (P < 0.05). The amount of subcutaneous fat affected the detection rate of the ASA (P < 0.05) but not the AKA. In CT scans of ASA detection, the mean CT values in the aorta at the arch and at T11 were 360 and 358 HU, respectively, whereas in CT scans without ASA detection, the CT values in the aorta at the arch and at T11 were lower (P < 0.05), 297 and 317 HU, respectively. The ASA and AKA were less frequently detected in our cohort than previous reports. The visualization of the ASA and AKA was significantly affected by aortic enhancement, the "vertebral mass index", and the contrast-to-noise ratio.


Effectiveness of powered hospital bed movers for reducing physiological strain and back muscle activation.
Battery powered bed movers are becoming increasingly common within the hospital setting. The use of powered bed movers is believed to result in reduced physical efforts required by health care workers, which may be associated with a decreased risk of occupation related injuries. However, little work has been conducted assessing how powered bed movers impact on levels of physiological strain and muscle activation for the user. The muscular efforts associated with moving hospital beds using three different methods; powered StaminaLift Bed Mover (PBM1), powered Gzunda Bed Mover (PBM2) and manual pushing were measured on six male subjects. Fourteen muscles were assessed moving a weighted hospital bed along a standardized route in an Australian hospital environment. Trunk inclination and upper spine acceleration were also quantified. Powered bed movers exhibited significantly lower muscle activation levels than manual pushing for the majority of muscles. When using the PBM1, users adopted a more upright posture which was maintained while performing different tasks (e.g. turning a corner, entering a lift), while trunk inclination varied considerably for manual pushing and the PBM2. The reduction in lower back muscular activation levels may result in lower incidence of lower back injury.


Structure and chemistry of epitaxial ceria thin films on yttria-stabilized zirconia substrates, studied by high resolution electron microscopy.
We have applied aberration-corrected transmission electron microscopy (TEM) imaging and electron energy loss spectroscopy (EELS) to study the structure and chemistry of epitaxial ceria thin films, grown by pulsed laser deposition onto (001) yttria-stabilized zirconia (YSZ) substrates. There are few observable defects apart from the expected mismatch interfacial dislocations and so the films would be expected to have good potential for applications. Under high electron beam dose rate (above about 6000 e-/Å2s) domains of an ordered structure appear and these are interpreted as being created by oxygen vacancy ordering. The ordered structure does not appear at lower lose rates (ca. 2600 e-/Å2s) and can be removed by imaging under 1 mbar oxygen gas in an environmental TEM. EELS confirms that there is both oxygen deficiency and the associated increase in Ce3+ versus Ce4+ cations in the ordered domains. In situ high resolution TEM recordings show the formation of the ordered domains as well as atomic migration along the ceria thin film (001) surface.


Extent of copper tolerance and consequences for functional stability of the ammonia-oxidizing community in long-term copper-contaminated soils.
Adaptation of soil microbial communities to elevated copper (Cu) concentrations has been well documented. However, effects of long-term Cu exposure on adaptation responses associated with functional stability and structural composition within the nitrifying community are still unknown. Soils were sampled in three field sites (Denmark, Thailand, and Australia) where Cu gradients had been established from 3 to 80 years prior to sampling. In each field site, the potential nitrification rate (PNR) decreased by over 50% with increasing soil Cu, irrespective of a 20 to >200-fold increase in Cu tolerance (at the highest soil Cu) among the nitrifying communities. This increased tolerance was associated with decreasing numbers (15-120-fold) of ammonia-oxidizing bacteria (AOB), except in the oldest contaminated field site, decreasing numbers of ammonia-oxidizing archaea (AOA; 10-130-fold) and differences in the operational taxonomic unit (OTU) composition of the AOB and, to a lesser extent, AOA communities. The sensitivity of nitrifying communities, previously under long-term Cu exposure, to additional stresses was assessed. Nitrification in soils from the three field sites was measured following acidification, pesticide addition, freeze-thaw cycles, and dry-rewetting cycles. Functional stability of the nitrification process was assessed immediately after stress application (resistance) and after an additional three weeks of incubation (resilience). No indications were found that long-term Cu exposure affected the sensitivity to the selected stressors, suggesting that resistance and resilience were unaffected. It was concluded that the nitrifying community changed structurally in all long-term Cu-exposed field sites and that these changes were associated with increased Cu tolerance but not with a loss of functional stability.