Disruption of a Transcriptional Repressor by an Insertion Sequence Element Integration Leads to Activation of a Novel Silent Cellobiose Transporter in Lactococcus lactis MG1363.
Lactococcus lactis subsp. cremoris strains typically carry many dairy niche-specific adaptations. During adaptation to the milk environment these former plant strains have acquired various pseudogenes and insertion sequence elements indicative of ongoing genome decay and frequent transposition events in their genomes. Here we describe the reactivation of a silenced plant sugar utilization cluster in an L. lactis MG1363 derivative lacking the two main cellobiose transporters, PtcBA-CelB and PtcBAC, upon applying selection pressure to utilize cellobiose. A disruption of the transcriptional repressor gene llmg_1239 by an insertion sequence (IS) element allows expression of the otherwise silent novel cellobiose transporter Llmg_1244 and leads to growth of mutant strains on cellobiose. Llmg_1239 was labeled CclR, for cellobiose cluster repressor.IMPORTANCE Insertion sequences (ISs) play an important role in the evolution of lactococci and other bacteria. They facilitate DNA rearrangements and are responsible for creation of new genetic variants with selective advantages under certain environmental conditions. L. lactis MG1363 possesses 71 copies in a total of 11 different types of IS elements. This study describes yet another example of an IS-mediated adaptive evolution. An integration of IS981 or IS905 into a gene coding for a transcriptional repressor led to activation of the repressed gene cluster coding for a plant sugar utilization pathway. The expression of the gene cluster allowed assembly of a novel cellobiose-specific transporter and led to cell growth on cellobiose.


Stable expression of FoxA1 promotes pluripotent P19 embryonal carcinoma cells to be neural stem-like cells.
FoxA1 belongs to the fork head/winged-helix transcription factor family and participates in stimulating neuronal differentiation of pluripotent stem cells at early stages. To explore the biological roles of FoxA1 during this process, the stable expression of a GFP-FoxA1 fusion protein was established in P19 pluripotent embryonal carcinoma cells. Although they still express pluripotency-related transcription factors such as Oct4, Nanog, and Sox2, the generated P19 GFPFoxA1 cells exhibited a decreased activity of alkaline phosphatase and an increased expression of SSEA-3 compared with P19 cells. Elevated levels of nestin expression and prominin-1+ populations were observed in P19 GFPFoxA1 cells, implicating that the stable expression of FoxA1 promoted P19 cells to gain partial characteristics of neural stem cells. Furthermore, the promoter of nestin was confirmed to be bound and activated by FoxA1 directly. The expression of neuron-specific marker tubulin betaIII also existed in P19 GFPFoxA1 cells. P19 GFPFoxA1 cells showed an earlier onset of differentiation during RA-induced neuronal differentiation, evidenced by a more rapid change on the Nanog decrease and the tubulin betaIII increase. Thus, overexpression of FoxA1 alone may promote pluripotent P19 cells to become neural stem-like cells.


Brain abscess caused by Porphyromonas gingivalis and Eubacterium nodatum mimicking acute stroke.
We described a case of a 65-year-old man with a brain abscess caused by Porphyromonas gingivalis and Eubacterium nodatum. The patient presented right central facial nerve palsy, mutism and right hemiparesis at the examination. The patient underwent a left frontal craniotomy with evacuation of the brain abscess. Specimens were collected for microbiological analysis and intravenous treatment was started with levetiracetam, dexamethasone, meropenem (1 g/8 h) and linezolid (600 mg/12 h). After identification of anaerobic bacteria the antibiotic treatment was changed to piperacillin/tazobactam (4 g/0,5 g/8 h), fulfilling 8 weeks of antibiotic with good clinical and radiological evolution.


Advanced carrier squeezing interferometry: a technique to suppress gamma distortion in fringe projection profilometry.
An advanced carrier squeezing interferometry (CSI) technique is proposed to suppress gamma distortion in fringe projection profilometry. CSI combines phase-shifted fringes into a single spatial-temporal fringe and then extracts the phase from its frequency spectrum. Although it has the property of rejecting high-order harmonics, the traditional CSI technique uses an approximate model that generates extra disturbance lobes in the process of phase extraction from the frequency domain. Therefore, the filter window used to extract the phase has to be very narrow, which results in the extra loss of high-frequency information. In this paper, we improve the approximate model by introducing a phase-correction term and encoding it into the projected standard fringes. Then, there are no extra disturbance lobes in the spectrum, and the acceptable filter window to reject high-order harmonics can be much wider. Thus, it is possible to preserve more high-frequency information in the retrieved phase. We performed simulations and experiments to validate the ability of this method to suppress gamma distortion and preserve high-frequency information as compared to the traditional CSI method.


Establishment of Simple Nomograms for Predicting Axillary Lymph Node Involvement in Early Breast Cancer.
Axillary lymph node (ALN) involvement is an important prognostic factor of early invasive breast cancer. The objective of this study was to establish simple nomograms for predicting ALN involvement based on ultrasound (US) characteristics and evaluate the predictive value of US in the detection of ALN involvement. A total of 1328 patients with cT1-2N0 breast cancer by physical exam were retrospectively analyzed. Univariate analysis was used for the comparison of variables, and multivariate analysis was performed by binary logistic regression analysis. The R software was used to establish simple nomograms based on the US characteristics alone. The receiver operating characteristic (ROC) curves of the prediction model and the verification group were drawn, and the area under the curve (AUC) was calculated to evaluate the discrimination of the prediction model. A calibration curve was plotted to assess the nomogram predictions vs the actual observations of the ALN metastasis rate and axillary tumor burden rate. The ALN metastasis rates of the training group and the validation group were 35.1% and 34.1%, respectively. Multivariate analysis showed that molecular subtype, lymphovascular invasion, mass descriptors (size, margin, microcalcification and blood flow signal) and LN descriptors (shape, cortical thickness and long-to-short ratio) were independent impact factors in early breast cancer. The AUC of ALN metastasis rate of prediction model based on US features was 0.802, the AUC of high tumor burden rate was 0.873, and the AUC of external validation group was 0.731 and 0.802, respectively. The calibration curve of the nomogram showed that the nomogram predictions are consistent with the actual metastasis rate and the high tumor burden rate. The results showed that preoperative US had a sensitivity of 59.4% and a specificity of 88.9% for predicting the ALN metastasis rate. The successfully established nomograms based on US characteristics to predict ALN metastasis rate and high axillary tumor burden rate in early breast cancer can achieve individual prediction. Compared with other nomogram predictions, it is more intuitive, and can help clinical decision-making; thus, it should be promoted. However, at this time US features alone are insufficient to replace sentinel lymph node biopsy.


Petrous apicitis: surgical anatomy.
Various surgical approaches to the petrous apex for exposure and drainage of suppurative processes are available to the otologist. The petrous apex may be conveniently divided into anterior and posterior portions by a line in the coronal plane through the internal auditory canal. The approach to the posterior petrous apex follows fistulous tracts in the sinodural angle, the subarcuate fossa, and the infralabyrinthine tract. The anterior petrous apex may be entered by means of a radical mastoidectomy. Fistulous tracts into an infected anterior petrous apex may be found through the hypotympanum, below the cochlea, through a triangle anterior to the cochlea, below the middle fossa dura, and above the carotid artery. In this approach to the petrous tip, one must have a thorough knowledge of the anatomical relationships around the carotid artery and cochlea: the carotid artery lies within 1.69 +/- 0.70 mm of the cochlea anteriorly, and the carotid artery may be exposed within the middle ear.


Manometry with needle cholangiography. Results in 70 patients.
Cholangiomanometry is evaluated in 70 patients using a new technique based on needle cholangiography. In 94% of the patients the results of cholangiomanometry were in agreement with the final operative diagnosis. In two patients out of 20, common duct stones did not cause changes in the biliary pressure. In 14 patients re-operated on for postcholecystectomy pains, the increase in intrabiliary pressure due to a fentanyl dose was significantly higher than that in the control patients. Cholangiomanometry is recommended for selective use to complement needle cholangiography in biliary re-operations and in operations after biliary pancreatitis.


The origin of spontaneous electrical activity at the end-plate zone.
Two types of spontaneous electrical activity are present at the end-plate zone: low-voltage negative potentials that correspond to miniature end-plate potentials, and larger voltage negative-positive potentials. The electrogenic origin of the latter has been uncertain. The origin of these larger potentials was investigated in the rat phrenic nerve diaphragm preparation and in human gastrocnemius muscle just prior to intubation during administration of preoperative anesthesia. In the hemidiaphragm the larger voltage negative-positive potentials were rarely triggered by intracellular or tungsten microelectrodes. The negative-positive potentials, however, were clearly triggered by contact of the concentric needle electrode with muscle hemidiaphragm at the end-plate region. The potentials were abolished by curare. Likewise, the equivalent potentials observed at the human gastrocnemius end-plate zone were blocked by neuromuscular blocking agents. Therefore, these positive-negative discharges represent postsynaptic muscle fiber action potentials and not nerve fiber activity. They were probably presynaptically activated by mechanical irritation of the motor axon terminal and preterminal branches.


Prognostic factors in women with breast cancer: distribution by socioeconomic status and effect on differences in survival.
To quantify and investigate differences in survival from breast cancer between women resident in affluent and deprived areas and define the contribution of underlying factors to this variation. Analysis of two datasets relating to breast cancer patients in Scotland: (1) population-based cancer registry data; (2) a subset of cancer registration records supplemented by abstraction of prognostic variables (stage, node status, tumour size, oestrogen receptor (ER) status, type of surgery, use of radiotherapy and use of adjuvant systemic therapy) from medical records. Scotland. (1) Cancer registration data on 21,751 women aged under 85 years diagnosed with primary breast cancer between 1978 and 1987; (2) national clinical audit data on 2035 women aged under 85 years diagnosed with primary breast cancer during 1987 for whom adequate medical records were available. Survival differences of 10% between affluent and deprived women were observed in both datasets, across all age groups. In the audit dataset, the distribution of ER status varied by deprivation group (65% ER positive in affluent group v 48% ER positive in deprived group; under 65 age group). Women aged under 65 with non-metastatic disease were more likely to have breast conservation than a mastectomy if they were affluent (45%) than deprived (32%); the affluent were more likely to receive endocrine therapy (65%) than the deprived (50%). However, these factors accounted for about 20% of the observed difference in survival between women resident in affluent and deprived areas. Deprived women with breast cancer have poorer outcomes than affluent women. This can only partly be explained by deprived women having more ER negative tumours than affluent women. Further research is required to identify other reasons for poorer outcomes in deprived women, with a view to reducing these survival differences.


Prevention of ischemic stroke: surgery.
The last 15 years have witnessed a resurgence of the role of surgical options for prevention of ischemic stroke. The landmark randomized trials including NASCET and ECST were published and explored the role of carotid endarterectomy in this regard. Patients with high grade stenosis of the internal carotid artery (> or = 70%) with prior TIA or minor non disabling stroke in the same territory were shown to have significant benefit of the procedure compared to best medical treatment. Benefit was comparatively less in patients with moderate grade stenosis of the ICA (50-69%). Surgical treatment of patients with <50% stenosis of the ICA resulted in worse outcomes compared to medical therapy and is consequently not recommended. These studies also standardized the method for measuring the degree of ICA stenosis. The ACAS and ACST studies attempted to resolve the rather vexing issue of surgical treatment of patients with asymptomatic ICA stenosis. The risk benefit ratio in asymptomatic patients is low and depends to a large extent on a low perioperative complication rate. Studies have also attempted to identify the best medical treatment in the perioperative period during CEA. Low dose aspirin has been shown to be beneficial, but the role of statins and betablockers is promising but yet uncertain. Ischemic stroke is a common complication after CABG. In this regard surgeons have differed in their approaches to performing CEA, some preferring to do it during the bypass surgery, while others prefer a two staged procedure. The surgical treatment of complete carotid occlusion by EC-IC bypass surgery has also enjoyed renewed interest and results of the COSS study are awaited keenly. The EC-IC bypass surgical procedure is also beneficial in moya-moya disease.


Atypical late presentation of muscular metastasis of melanoma in the contralateral limb.
A man in his 50s presented to plastic surgery again with a lesion on his left upper arm. He had previously been treated for a malignant melanoma (MM) on his right arm over 5 years earlier. Sentinel lymph node biopsy (SLNB) had been negative, and he had completed the recommended 5 years follow-up period. Imaging was suspicious for an intramuscular soft tissue malignancy within the triceps muscle. After discussion with the regional sarcoma service, a core biopsy was performed. Histopathology suggested a diagnosis of metastatic MM, which was confirmed after surgical excision. This case highlights a rare example of an isolated muscular metastasis of MM, which presented at a distant site, over 5 years from the original treatment. This case highlights the unpredictable nature of MM, reminding clinicians of the need for a low threshold for investigation of soft tissue masses in patients with a history of cutaneous malignancy.


Levonorgestrel-releasing intrauterine system placement for severe uterine cervical stenosis after conization: two case reports.
Several approaches for treating severe uterine cervical stenosis after conization for cervical intraepithelial neoplasia have been reported; yet, the condition can still be difficult to treat successfully. We performed uterine cervical dilation surgery in two patients with severe stenosis, followed by insertion of the levonorgestrel-releasing intrauterine system, which is used for dysmenorrhea or endometriosis-related pain because of its strong progesterone activity. Patient 1 was a 34-year-old Japanese woman who was diagnosed with dysmenorrhea caused by recurrent uterine cervical stenosis and hematometra after laser conization. Patient 2 was a 44-year-old Japanese woman who developed dysmenorrhea and prolonged menstruation caused by uterine cervical stenosis without hematometra. After providing informed consent, they underwent cervical dilation surgery followed by insertion of the levonorgestrel-releasing intrauterine system. After treatment, their symptoms immediately improved, and after removal of their devices, they remained asymptomatic. To the best of our knowledge, this is the first report to confirm the usefulness and easy applicability of the levonorgestrel-releasing intrauterine system for uterine cervical stenosis. Although we had success with the method, this study of two patients is preliminary. Further study with larger numbers of patients is necessary to confirm the usefulness of our technique.


The impact of social communication on perceived HPV vaccine effectiveness in a low-income, minority population.
Perceived vaccine effectiveness is linked to vaccine-uptake. This study aims to determine if hearing about the HPV vaccine from family/friends (social source) or discussing the vaccine with family/friends (social discussion) is associated with perceived HPV vaccine effectiveness among female ethnic-minority, medical-decision-makers of vaccine-eligible girls. Data come from a cross-sectional HPV vaccine telephone-survey administered by the Los Angeles County Office of Women's Health (OWH) hotline operators between January-November 2009. Among survey participants who reported awareness of the HPV vaccine (n=294), two logistic regression models of perceived HPV vaccine effectiveness were conducted; a source of information model with social source as the main predictor, and a discussion model with social discussion as the main predictor. These were adjusted for medical source and medical discussion, and covariates affecting interaction with the health care system. Women who heard about the HPV vaccine from a social source were more likely to perceive the vaccine as effective compared to those who did not report a social source of information (adjusted OR 4.78, 95% CI 1.76-12.98). Medical source of information was also associated with perceived vaccine effectiveness (adjusted OR 2.07, 95% CI 1.06-4.05). Those who reported social discussion, but not those who discussed the vaccine with a medical provider, had increased odds of perceived vaccine effectiveness (adjusted OR 1.98, 95% CI 1.04-3.78). Social source of information and social discussion were associated with perceived HPV vaccine effectiveness; this highlights the value of social communication among low-income minority women, and the need for vaccine-messaging interventions that utilize a social network approach.(Ethn Dis. 2011;21(4):495-501)


Praxis-induced reflex seizures in two Japanese cases with ring chromosome 20 syndrome.
Ring chromosome 20 syndrome is an epileptic and neurodevelopmental encephalopathy that occurs in children, characterised by a triad of refractory frontal lobe seizures, recurrent non-convulsive status epilepticus and frontal lobe-dominant paroxysmal discharges. However, details of other clinical features associated with ring chromosome 20 syndrome remain unknown. Here, we report two patients with ring chromosome 20 syndrome who had praxis-induced reflex seizures. Case 1 was an 11-year-old girl who presented with seizures triggered by specific activities such as mental and written calculations, writing, decision-making, recall, sudden changes in routine or ambient temperature and bathing. During calculations, left frontal lobe-dominant, 3-Hz slow-wave bursts were observed on EEG. Lacosamide effectively suppressed her tonic seizures. Case 2 was a six-year-old boy who presented with seizures triggered by specific activities such as calculations, recall and bathing. During calculations, frontal lobe-dominant, 3-Hz spike and slow-wave bursts were observed on EEG. Although his epilepsy was refractory, gabapentin reduced the frequency of focal seizures. In both cases, the hyperexcitability in the frontal lobe may have spread to the motor cortex and precipitated praxis-induced seizures. Therefore, in addition to the known characteristic triad, praxis-induced reflex seizures may also be a feature of ring chromosome 20 syndrome.


Generation of large-scale vorticity in a homogeneous turbulence with a mean velocity shear.
An effect of a mean velocity shear on a turbulence and on the effective force which is determined by the gradient of the Reynolds stresses is studied. Generation of a mean vorticity in a homogeneous incompressible nonhelical turbulent flow with an imposed mean velocity shear due to an excitation of a large-scale instability is found. The instability is caused by a combined effect of the large-scale shear motions ("skew-induced" deflection of equilibrium mean vorticity) and "Reynolds stress-induced" generation of perturbations of mean vorticity. Spatial characteristics of the instability, such as the minimum size of the growing perturbations and the size of perturbations with the maximum growth rate, are determined. This instability and the dynamics of the mean vorticity are associated with Prandtl's turbulent secondary flows.


Prevalence of occupational exposure to carcinogens among workers of Arabic, Chinese and Vietnamese ancestry in Australia.
Although job-related diseases result in more deaths per year than job-related injuries, most research concerning ethnic minority workers has concerned accidents and injuries rather than disease-causing exposures such as carcinogens. We conducted a telephone-based cross-sectional survey to estimate the prevalence of occupational exposure to carcinogens among a sample of ethnic minority workers in Australia, and compared their exposure prevalence to that of a sample of the general Australian-born working population ('Australian workers'). One-third of the ethnic minority workers were exposed to at least one carcinogen at work. The likelihood of exposure to carcinogens was not significantly different from that of Australian workers, although the likelihood of exposure to individual carcinogens varied by ethnicity. Knowing the prevalence of exposure to carcinogens in the workplace in different ethnic groups will allow better targeted and informed occupational health and safety measures to be implemented where necessary.


On the prevention and analysis of missing data in randomized clinical trials: the state of the art.
We summarize and elaborate on the recently published National Research Council report entitled "The Prevention and Treatment of Missing Data in Clinical Trials." We tailor our discussion to orthopaedic trials. In particular, we discuss the intent-to-treat principle, review study design and prevention ideas to minimize missing data, and present state-of-the-art sensitivity analysis methods for analyzing and reporting the results of studies with missing data.


Performance of a revised cardiac troponin method that minimizes interferences from heterophilic antibodies.
Recent guidelines for use of cardiac troponin to detect cardiac damage and for cardiovascular risk stratification have made increasingly sensitive troponin assays important. Troponin assays continue to be plagued by interferences caused by heterophilic antibodies (HAs). We evaluated the performance of a revised cardiac troponin I (cTnI) assay designed to have increased analytical sensitivity and to minimize the effect of HAs. The revised Dade Behring Dimension cTnI assay was evaluated according to NCCLS EP5-A at five institutions. Plasma samples from 14 309 patients were assayed by the original Dimension cTnI assay. To identify samples that may have interfering HAs, samples with values >1.4 microg/L were reanalyzed on the Dade Behring Stratus CS cTnI assay. Samples with possible interfering antibodies were also analyzed before and after selective absorbance studies on the revised Dade Behring Dimension cTnI assay. The limit of quantification in the revised method was 0.1 microg/L with imprecision (CV) of 11-17% at 0.1 microg/L. Values correlated well with the Stratus CS cTnI method: revised = 1.06(original) + 0.01; r = 0.98, S(y/x) = 0.25 microg/L). Falsely increased results consistent with myocardial infarction by the original Dimension cTnI assay and presumably attributable to HAs were identified in 0.17% of all patients with samples submitted for cTnI analysis. The revised Dimension cTnI assay eliminated the interference in 17 of 25 samples identified and greatly decreased the interference in the other 8. The revised Dimension cTnI method greatly minimizes the effect of interfering HAs. It also exhibits analytical performance characteristics consistent with recent guidelines for use of this assay to detect cardiac damage.


Organization and maintenance of Drosophila telomeres: the roles of terminin and non-terminin proteins.
Drosophila telomeres are elongated by occasional transposition of specialized retroelements rather than telomerase activity, and are assembled independently of the sequence of the DNA termini. Drosophila telomeres are capped by terminin, a complex formed by the HOAP, Moi, Ver and HipHop proteins that localize exclusively at telomeres and protect them from fusion events. Other proteins required to prevent end-to-end fusion include HP 1 Eff/UbcD 1, ATM, the components of the Mrel 1-Rad50-Nbs (MRN) complex, and the Woc transcription factor. The terminin proteins are encoded by fast-evolving genes and are not evolutionarily conserved outside the Drosophila species. In contrast, the non-terminin telomere capping proteins are not fast-evolving, do not localize only at telomeres and are conserved from yeasts to mammals. We propose that following telomerase loss, Drosophila rapidly evolved terminin to bind chromosome ends in a sequence-independent manner, and that non-terminin proteins did not evolve as rapidly as terminin because of the functional constraints imposed by their involvement in diverse cellular processes. This hypothesis suggests that the Drosophila non-terminin proteins might correspond to ancestral telomere-associated proteins with homologues in other organisms including humans.


Does cerebral hypoxia facilitate central fatigue?
What is the topic of this review? This review addresses whether a mismatch between cerebral O2 demand and delivery accelerates the development of central fatigue during endurance-type exercise. What advances does it highlight? The difficulty with studying the importance of cerebral O2 availability for exercise performance is to manipulate cerebral O2 availability independently of muscular O2 availability. The different approaches to overcome this limitation indicate that cerebral oxygenation is not a major limiting factor in normoxia, but may limit performance in submaximal exercise tasks in hypoxia. Central fatigue originates within the central nervous system and is characterized by a decrease in voluntary muscle activation. Reduced systemic O2 availability can facilitate central fatigue by enhancing the afferent input of the chemosensitive nerves that play a pivotal role in development of central fatigue. There is accumulating evidence that, in some situations, inadequate O2 availability to the brain itself promotes central fatigue. This short review presents some of the recent findings supporting a direct effect of inadequate cerebral O2 availability on central fatigue and addresses the persisting limitations.


On learning vector-valued functions.
In this letter, we provide a study of learning in a Hilbert space of vectorvalued functions. We motivate the need for extending learning theory of scalar-valued functions by practical considerations and establish some basic results for learning vector-valued functions that should prove useful in applications. Specifically, we allow an output space Y to be a Hilbert space, and we consider a reproducing kernel Hilbert space of functions whose values lie in Y. In this setting, we derive the form of the minimal norm interpolant to a finite set of data and apply it to study some regularization functionals that are important in learning theory. We consider specific examples of such functionals corresponding to multiple-output regularization networks and support vector machines, for both regression and classification. Finally, we provide classes of operator-valued kernels of the dot product and translation-invariant type.


Glucose control in the UKPDS: what did we learn?
The UK Prospective Diabetes Study (UKPDS) set out to establish whether improved glucose control could alleviate the macrovascular and microvascular complications of diabetes and to compare the relative merits of diet, oral glucose-lowering agents or insulin in achieving this objective. The study broke many of the rules of trial design, not least by constant addition of further interventions and analyses, but this flexibility would, paradoxically, prove to be one of its greatest strengths. The UKPDS taught us that glucose control must be tackled aggressively in Type 2 diabetes. It taught us that treatment must be escalated in parallel with the evolution of pancreatic B-cell failure. It also taught us that glucose control is not enough: the central objective of therapy is to reduce vascular risk by any means available. This commentary looks back along the winding road that led to these conclusions.


Bredemolic acid restores glucose utilization and attenuates oxidative stress in palmitic acid-induced insulin-resistant C2C12 cells.
Objective. Due to insulin resistance and oxidative stress that are associated with type 2 diabetes mellitus (T2DM), T2DM has become a prevalent metabolic disorder that presents various side effects. However, alternative antidiabetic treatment has commonly been used in treating diabetes mellitus in diabetic patients. In our previous studies, bredemolic acid has been reported as an antidiabetic agent that improves glucose uptake, ameliorates insulin resistance, and oxidative stress in the liver, heart, kidney, and skeletal muscle of prediabetic rats. However, these effects have not been validated in vitro. Therefore, this study was aimed to investigate the effects of bredemolic acid on insulin-mediated glucose utilization, lipid peroxidation, and the total antioxidant capacity (TOAC) in palmitic acid-induced insulin-resistant C2C12 skeletal muscle cells in vitro. Methods. Insulin resistance was induced in the skeletal muscle cells after 4 h of exposure to palmitic acid (0.5 mmol/l). Different cell groups were incubated in culture media DMEM supplemented with fetal calf serum (10%), penicillin/streptomycin (1%), and L-glutamine (1%) and then treated with either insulin (4 µg/ml) or bredemolic acid (12.5 mmol/l) or with both. Thereafter, the cells were seeded in 24- or 96-well plates for determination of the cell viability, glucose utilization, glycogen formation, and antioxidant capacity. Results. The results showed that bredemolic acid significantly improved TOAC and promoted glucose utilization via attenuation of lipid peroxidation and increased glycogen formation in the insulin-resistant cells, respectively. Conclusion. This study showed that bredemolic acid restored the insulin resistance through improved glucose utilization, glycogen formation, and TOAC in the skeletal muscle cells.


Dendritic cells: ontogeny.
Dendritic cells (DC) play key rolls in various aspects of immunity. The functions of DC depend on the subsets as well as their location or activation status. Understanding developmental lineages, precursors and inducing factors for various DC subsets would help their clinical application, but despite extensive efforts, the precise ontogeny of various DC, remain unclear and complex. Because of their many functional similarities to macrophages, DC were originally thought to be of myeloid-lineage, an idea supported by many in vitro studies where monocytes or GM-CSF (a key myeloid growth factor) has been extensively used for generating DC. However, there has been considerable evidence which suggests the existence of lymphoid-lineage DC. After the confusion of myeloid-/lymphoid-DC concept regarding DC surface markers, we have now reached a consensus that each DC subset can differentiate through both myeloid- and lymphoid-lineages. The identification of committed populations (such as common myeloid- and lymphoid progenitors) as precursors for every DC subsets and findings from various knockout (KO) mice that have selected lymphoid- or myeloid-lineage deficiency appear to indicate flexibility of DC development rather than their lineage restriction. Why is DC development so flexible unlike other hematopoitic cells? It might be because there is developmental redundancy to maintain such important populations in any occasions, or such developmental flexibility would be advantageous for DC to be able to differentiate from any "available" precursors in situ irrespective of their lineages. This review will cover ontogeny of conventional (CD8 +/- DC) DC, plasmacytoid DC and skin Langerhans cells, and recently-identified many Pre-DC (immediate DC precursor) populations, in addition to monocytes and plasmacytoid DC, will also be discussed.


Proteoglycans affect monomer infiltration in the etch-and-rinse bonding technique.
To identify proteoglycans (PGs) and collagen fibrils (CF) within human dentin by means of a dual immunofluorescent labeling technique and to investigate the monomer infiltration of two etch-and-rinse adhesives to tosyl-phenylalanine chloromethyl-ketone (TPCK)-treated trypsin (TRY)-pretreated dentin. Thirty-micrometer sections of middle coronal dentin were obtained and etched with 37% phosphoric acid gel for 15 s. After preconditioning with or without TRY digestion, the sections were subjected to dual immunofluorescent labeling and observed with a confocal laser scanning microscope (CLSM). Demineralized dentin matrixes treated with or without TRY were observed with field emission scanning electron microscope (FE-SEM). Two etch-and-rinse adhesives, Adper Single Bond 2 (SB) and Prime & Bond NT (PBNT), were applied to the dentin surfaces that were pretreated with or without TRY. The thickness of the hybrid layers was evaluated under confocal micro-Raman spectroscopy and analyzed with a two-way ANOVA. Green and red fluorescence was used to represent the PGs and the CF that were colocalized in the same section with different distributions. PGs were localized in the lumens of the dentin tubules and in peritubular dentin, while the type-I collagen fibrils were localized in intertubular dentin and peritubular dentin. After preconditioning with TRY digestion, the red fluorescence decreased or disappeared, the organic filaments in the lumens of the dentin tubules disappeared, the tubules were enlarged, and the hybrid layer thickness for adhesives bonded to the TRY-pretreated dentin surfaces were significantly increased (p<0.001 for both SB and PBNT). The dual immunofluorescence labeling methodology can be used to study the human dentin matrix without decalcifying the entire dentin fragment. Proteoglycans were localized in the lumens of the dentin tubules and in peritubular dentin, which could depress the infiltration of the adhesive resin monomers. The use of TRY digestion increased the thickness of the hybrid layer created by the tested two-step etch-and-rinse adhesive.


Facet Preserving Technique by En Bloc Flavectomy in Microscopic Posterior Decompression Surgery for Lumbar Spinal Stenosis: Semicircumferential Decompression (SCD).
Posterior decompression surgery which enlarges the spinal canal in cases with lumbar spinal stenosis is the most fundamental technique in spine surgery, but controversy still remains for the exact technique. Because nerve roots run under the ventral side on the superior articular process (SAP), achieving both facet joint preservation and nerve root decompression is problematic. In conventional laminotomies or laminectomies, medial facetectomies are performed to decompress the nerve root, but it is ideal to preserve the facet joints completely for preserving joint stability. We handle this problem with an original decompression technique, called "semicircumferential decompression." The main features of this procedure are an en bloc flavectomy and total preservation of facet joints. The procedure is performed under the microscope with a midline approach. The flavum is detached from the ventral surface of the SAP using a currete without disturbing the SAP. The facet joints are preserved completely. The advantage of an en bloc flavectomy is that we can remove the flavum attachment to the ventral surface of SAP totally without a medial facetectomy. Since 1991, we have performed this technique in more than 5000 cases. In this paper, we will explain the tips, pitfalls, and advantages of this technique.


Functional evaluation of the diaphragm with a noninvasive test.
Cardiac surgery with median sternotomy causes iatrogenic damage to the function of the diaphragm muscle that is both temporary and permanent. Myocardial infarction itself causes diaphragmatic genetic alterations, which lead the muscle to nonphysiological adaptation. The respiratory muscle area plays several roles in maintaining both physical and mental health, as well as in maximizing recovery after a cardiac event. The evaluation of the diaphragm is a fundamental step in the therapeutic process, including the use of instruments such as ultrasound, magnetic resonance imaging (MRI), and computed axial tomography (CT). This article reviews the neurophysiological relationships of the diaphragm muscle and the symptoms of diaphragmatic contractile dysfunction. The authors discuss a scientific basis for the use of a new noninstrumental diaphragmatic test in the hope of stimulating research.


GPER activates Notch signaling in breast cancer cells and cancer-associated fibroblasts (CAFs).
The G protein-coupled receptor GPR30/GPER has been shown to mediate rapid effects of 17β-estradiol (E2) in diverse types of cancer cells. Here, we provide evidence for a novel crosstalk between GPER and the Notch signaling pathway in breast cancer cells and cancer-associated fibroblasts (CAFs). We show that E2 and the GPER selective ligand G-1 induce both the γ-secretase-dependent activation of Notch-1 and the expression of the Notch target gene Hes-1. These inductions are prevented by knocking down GPER or by using a dominant-negative mutant of the Notch transcriptional co-activator Master-mind like-1 (DN-MAML-1), hence suggesting the involvement of GPER in the Notch-dependent transcription. By performing chromatin-immunoprecipitation experiments and luciferase assays, we also demonstrate that E2 and G-1 induce the recruitment of the intracellular domain of Notch-1 (N1ICD) to the Hes-1 promoter and the transactivation of a Hes-1-reporter gene, respectively. Functionally, the E2 and G-1-induced migration of breast cancer cells and CAFs is abolished in presence of the γ-secretase inhibitor GSI or DN-MAML-1, which both inhibit the Notch signaling pathway. In addition, we demonstrate that E2 and G-1 prevent the expression of VE-Cadherin, while both compounds induce the expression of Snail, a Notch target gene acting as a repressor of cadherins expression. Notably, both GSI and DN-MAML-1 abolish the up-regulation of Snail-1 by E2 and G-1, whereas the use of GSI rescues VE-Cadherin expression. Taken together, our results prove the involvement of the Notch signaling pathway in mediating the effects of estrogenic GPER signaling in breast cancer cells and CAFs.


Maternal child-feeding style during the weaning period: association with infant weight and maternal eating style.
A controlling maternal child-feeding style has been show to have negative consequences for child weight and eating style for children over the age of 12 months. Maternal restriction is associated with increased consumption of food if given free access and child overweight. Pressure to eat conversely is associated with picky eating and a lower child weight. Little research however has considered the influence of maternal feeding style under 1 year, during the period when infants are being introduced to complementary foods. In the current study, 642 mothers with a child aged 6-12 months completed a copy of the Child Feeding Questionnaire (Birch, Fisher, Grimm-Thomas, Markey, Sawyer & Johnson 2001), the Dutch Eating Questionnaire (Van Strien, Frijters, Bergers, & Defares 1986) and reported infant and maternal weight. Differences in maternal feeding style were identifiable during this period and related to infant weight and maternal weight and eating style. Infant weight was positively correlated with maternal use of restriction, monitoring and concern for infant weight. Moreover, mothers high in restraint, external and emotional eating reported higher levels of concern for infant weight, restriction and monitoring and perceived their infants to be larger. The findings suggest that the extent to which controlling feeding practices are used is influenced by infant and maternal personal weight concerns even at this early stage. Potentially, these early behaviours could have long term consequences for child weight and eating style.


Seizure as the manifestation of relapse of multiple sclerosis in a military pilot.
A case of a seizure in an active pilot with multiple sclerosis is presented. A 40-yr-old Canadian Forces pilot experienced a secondary generalized tonic-clonic seizure while taxiing a CC-130 (Hercules) transport after landing. His multiple sclerosis had been in remission since 1997 and he had been returned to restricted flying duties. He was assessed and treated, with no further seizures or adverse sequelae. An MRI showed a new demyelinating lesion in the anterior corpus callosum. His seizure was the only clinical manifestation of his MS relapse. The prevalence of seizures in MS patients, possible causal mechanisms, and the disposition of pilots with MS are discussed.


Organizing pneumonia primed by high-dose chemotherapy and lung irradiation: two pediatric cases.
A 9-year-old and a 17-year-old male patients affected by metastatic Ewing sarcoma developed an organizing pneumonia after high-dose chemotherapy with autologous peripheral blood stem cell transplantation followed by total-lung irradiation. They were successfully treated with high-dose corticosteroid for 6 months slowly tapered, with a significant clinical and radiologic response. Organizing pneumonia is a nonspecific response to various forms of lung injury such as high-dose chemotherapy and radiotherapy. For this reason, even if rare, has to be considered in children affected by lung metastatic Ewing sarcoma with persisting pulmonary symptoms after peripheral blood stem cell transplantation and total-lung irradiation. This report provides a useful description for the evaluation and treatment of pediatric patients with pulmonary infiltrates after chemotherapy and radiotherapy.


The Use of Serum Methadone/Metabolite Ratios to Monitor Changing Perinatal Pharmacokinetics.
Pregnancy profoundly alters drug metabolism, accelerating clearance and confounding medication management, primarily through induction of CYP450 enzymes. Methadone is a CYP450 substrate with altered pharmacokinetics during pregnancy. We report on the use of serum methadone/metabolite ratios (MMRs) to monitor changes in methadone metabolism through the perinatal period and to objectively guide methadone dosing. Previous research found average MMRs in nonpregnant populations of between 11.3 and 12.7. Serum methadone and its major metabolite 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine concentrations were analyzed in 67 samples from 23 pregnant patients treated for opioid use disorder, and their calculated ratio was used to document changes in methadone clearance across trimesters and postpartum. Lower ratios indicate increased clearance. The average MMR during pregnancy was 6.1. Ratios declined significantly from trimester 1 to trimester 3 (P = 0.007), and then rose significantly from trimester 3 to postpartum (P = 0.001). The per cent of ratios that were 4 or less, indicating ultrarapid metabolism, increased from 8% to 30% to 38% across trimesters, and decreased to 5% postpartum. Forty-four per cent of individual patients had at least 1 prepartum ratio of 4 or less. This study documents significant metabolic changes occurring perinatally, which indicate the need for both changes in methadone dose and dose frequency to maintain maternal/fetal stability, and also dose reductions as hypermetabolism reverses postpartum. MMRs provide an objective tool to more efficiently improve the safety and efficacy of methadone dosing perinatally.


Indole-based hydrazide-hydrazones and 4-thiazolidinones: synthesis and evaluation as antitubercular and anticancer agents.
A new series of indolylhydrazones (6) and indole-based 4-thiazolidinones (7, 8) have been designed, synthesized and screened for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. 4-Thiazolidinone derivatives 7g-7j, 8g, 8h and 8j displayed notable antituberculosis (anti-TB) activity showing 99% inhibition at MIC values ranging from 6.25 to 25.0 µg/ml. Compounds 7g, 7h, 7i, 8h and 8j demonstrated anti-TB activity at concentrations 10-fold lower than those cytotoxic for the mammalian cell lines. The indolylhydrazone derivative 6b has also been evaluated for antiproliferative activity against human cancer cell lines at the National Cancer Institute (USA). Compound 6b showed an interesting anticancer profile against different human tumor-derived cell lines at sub-micromolar concentrations with obvious selectivity toward colon cancer cell line COLO 205.


[Characteristics of the immune response to staphylococcal anatoxin in healthy persons].
The immunization of young healthy males with adsorbed staphylococcal toxoid revealed the existence of two main types of postimmunization humoral response. One of them was characterized by an early (on days 7-14 after immunization) rise in the titer of antibodies with the subsequent gradual decrease of their content, while the number of circulating T-suppressors remained unchanged. The characteristic feature of the other type was a slow rise in the level of antitoxins by day 21 after immunization with the subsequent drop of their titers, preceded by a considerable increase in the number of circulating T-suppressors. The maximum antibody titer was definitely higher in the first type of response than in the second type (14.8 +/- 1.41 and 9.0 +/- 1.53 I. U./ml respectively). A single plasmapheresis procedure on day 21 after immunization produced no essential effect on the dynamics of the characteristics of cell-mediated and humoral immunity.


Tone audiometry control of children treated for meningitis with large intravenous doses of ampicillin.
Thirty-seven children treated for bacterial meningitis with ampicillin in high doses were followed up with audiometric control. Defects were recorded in 6 cases. Two of these were ascribed to chronic otosalpingitis. In 4 patients with sensorineural hearing loss, 3 were unilateral, and in only one case was the damage bilateral. Even here there was a previous history of hearing loss. A suggested ototoxicity of ampicillin could not be confirmed.


Expression islands clustered on the symbiosis island of the Mesorhizobium loti genome.
Rhizobia are symbiotic nitrogen-fixing soil bacteria that are associated with host legumes. The establishment of rhizobial symbiosis requires signal exchanges between partners in microaerobic environments that result in mutualism for the two partners. We developed a macroarray for Mesorhizobium loti MAFF303099, a microsymbiont of the model legume Lotus japonicus, and monitored the transcriptional dynamics of the bacterium during symbiosis, microaerobiosis, and starvation. Global transcriptional profiling demonstrated that the clusters of genes within the symbiosis island (611 kb), a transmissible region distinct from other chromosomal regions, are collectively expressed during symbiosis, whereas genes outside the island are downregulated. This finding implies that the huge symbiosis island functions as clustered expression islands to support symbiotic nitrogen fixation. Interestingly, most transposase genes on the symbiosis island were highly upregulated in bacteroids, as were nif, fix, fdx, and rpoN. The genome region containing the fixNOPQ genes outside the symbiosis island was markedly upregulated as another expression island under both microaerobic and symbiotic conditions. The symbiosis profiling data suggested that there was activation of amino acid metabolism, as well as nif-fix gene expression. In contrast, genes for cell wall synthesis, cell division, DNA replication, and flagella were strongly repressed in differentiated bacteroids. A highly upregulated gene in bacteroids, mlr5932 (encoding 1-aminocyclopropane-1-carboxylate deaminase), was disrupted and was confirmed to be involved in nodulation enhancement, indicating that disruption of highly expressed genes is a useful strategy for exploring novel gene functions in symbiosis.


Spectrum of pathogens of in-patient children and youths with community acquired pneumonia: a 3 year survey of a community hospital in Vienna, Austria.
No actual data are available on the epidemiology and morbidity of community acquired pneumonia (CAP) in youths and children in Vienna, Austria. The objective was to determine the epidemiology of CAP and morbidity of children hospitalized due to CAP in a tertiary care facility. During three winter seasons youths and children hospitalized due to CAP were enrolled. Testing for viral and bacterial pathogens of pneumonia was performed in a routine clinical setting. Blood cultures were performed; respiratory viruses, Mycoplasma pneumoniae and Chlamydia pneumoniae were searched for by an established Real Time polymerase chain reaction (PCR) panel. Clinical signs and indices of inflammation were documented. Out of 279 children and youths with CAP a causative agent could be detected in 190 (68 %). Viruses and bacteria were diagnosed in 107 (57 %) and 58 patients (30 %), respectively. Co-infection was found in 20 patients (10 %), Mycoplasma pneumoniae or Clamydia pneumoniae in 16 cases (8 %). In seven patients blood cultures were positive. C-reactive protein (CRP) was significantly higher in children with positive Streptococcus pneumoniae antigen (SPAG) than with viral infection and/or co-infection. Clinical parameters showed no statistically significant differences. C. pneumoniae and M. pneumoniae were only diagnosed in children and youths with 5 years and older. Testing for pathogens in CAP in clinical routine achieves a high recovery rate. Blood cultures are rarely helpful, but the molecular testing for viruses seemed to be helpful to establish the diagnosis.


Connectivity matters - ultrafast isomerization dynamics of bisazobenzene photoswitches.
We have investigated the ultrafast dynamics of o-, m- and p-bisazobenzenes, which represent elementary building blocks for photoswitchable multiazobenzene nanostructures. The connectivity pattern within bisazobenzenes and the ensuing complex interactions between the individual azobenzene units determines the ultrafast dynamics of these compounds and their photochemical properties. While retaining a relatively high E → Z isomerization quantum yield, o-bisazobenzene exhibits a very high thermal relaxation rate (half-life of 1.6 ms). Our theoretical calculations reveal that the geometry allows intramolecular excitonic interaction between the azobenzene units, which is reflected in the femtosecond transient absorption data via the simultaneous bleaching of the two excitonic bands. In contrast, the properties of m-bisazobenzene are very similar to the monomeric azobenzene, with the two units acting nearly independently from each other. The highest degree of π conjugation extending over the two azobenzene units was observed for p-bisazobenzene, which results in strong planarity of the molecule, reduced excited state lifetime and relatively low isomerization quantum yield. Multiphotochromic systems bridge the gap between molecular photoswitches and macroscopic function and thus, understanding the properties of bisazobenzenes opens the way to the design and development of new structures with extensive and versatile applications.


Induction of the nuclear receptor PPAR-γ by the cytokine GM-CSF is critical for the differentiation of fetal monocytes into alveolar macrophages.
Tissue-resident macrophages constitute heterogeneous populations with unique functions and distinct gene-expression signatures. While it has been established that they originate mostly from embryonic progenitor cells, the signals that induce a characteristic tissue-specific differentiation program remain unknown. We found that the nuclear receptor PPAR-γ determined the perinatal differentiation and identity of alveolar macrophages (AMs). In contrast, PPAR-γ was dispensable for the development of macrophages located in the peritoneum, liver, brain, heart, kidneys, intestine and fat. Transcriptome analysis of the precursors of AMs from newborn mice showed that PPAR-γ conferred a unique signature, including several transcription factors and genes associated with the differentiation and function of AMs. Expression of PPAR-γ in fetal lung monocytes was dependent on the cytokine GM-CSF. Therefore, GM-CSF has a lung-specific role in the perinatal development of AMs through the induction of PPAR-γ in fetal monocytes.


Ten years' evaluation of diet, anthropometry, and physical exercise adherence after islet allotransplantation.
Allogeneic islet transplantation (IT) provokes changes in metabolic responses and nutritional behaviors. The durability of these changes needs to be described as well as their impact on the recipients' lifestyle. The goal of this study was to investigate how islet transplantation influenced diet, exercise habits, and body composition during 10 years after IT. A retrospective study performed in 33 (14 males, 19 females) IT recipients used dietary, physical activity open- ended questionnaire and anthropometric measurements. Data were collected before transplantation, every 3 months up to the 18th and every 6 months thereafter. Data were grouped by gender and eras: pre-IT; 0-3 years; 4-6 years, and 7-10 years after IT. Reduction in body mass index (BMI) from pre-IT to 0-3 years was noted: 23.68 ± 2,18 kg/m(2) to 22.07 ± 2.94 kg/m(2) (P < .05). Increased values were observed from 0-3 years to 4-6 years in: waist circumference (WC) (76.68 ± 7.22 to 79.44 ± 7.58 cm), BMI (23,68 ± 2,18 to 22,75 ± 3,11 kg/m(2)) and weight (64.69 ± 11.98 to 67.43 ± 14 kg): (P < .03). WC increased continuously up to 7-10 years (86.33 ± 9.45 cm; P < .05). There was an average of 5.3 ± 5.6 h/wk of exercise during follow-up. From pre-IT to 0-3 years there was a 19% reduction in protein consumption (P < .05) and a 39% increase in calories from saturated fats (P < .05). A trend to reduce carbohydrates intake noted from pre-IT to 0-3 years was progressively inverted from then throughout 7-10 years (not significant). IT was associated with a significantly decreased BMI early on that it was not sustained. The subsequent weight gain and WC increase could be the result of chronic immunosuppressive therapy and/or voluntary change in eating habits. The increased consumption of carbohydrates could be related to an adaptation of a lifestyle or/and reintroduction of insulin after graft dysfunction. Active lifestyle might be result of the intensive clinical care after IT, concomitant awareness of the importance of routine physical exercise on blood glucose control, and diabetes management. Continuous follow-up of IT recipients is needed to better understand these changes and for comparison with subjects with type 1 diabetes mellitus.


Apoptosis of stomach cancer cell SGC-7901 and regulation of Akt signaling way induced by bovine lactoferrin.
Lactoferrin, a protein from bovine milk belonging to the transferring family proteins, contains 2 bound Fe(+3) ions. Recent research has revealed that lactoferrin exhibits not only antimicrobial activity by its high affinity for Fe(+3) but also remarkable anticancer capacity in cancer cell lines. Meanwhile, increasing evidence suggests that aberrant activation of Akt is involved in both normal cells and human cancers and that inhibition of Akt signaling pathway might be a promising strategy for cancer treatment. In the present study, we investigated the effect of the antitumor induced by exposing stomach cancer cell SGC-7901 to lactoferrin for 24 and 48 h. The cell viability was assessed by 3-(4,5)-dimethylthiahiazo(-z-yl)-3,5-di-phenytetrazoliumromide (MTT) assay and apoptosis was quantified by propidium iodide uptake and Annexin V-fluorescein isothiocyanate fluorescent probe label through flow cytometry. Our investigation indicates that inhibitory ratio of 50 microM lactoferrin for proliferation of stomach cancer cell SGC-7901 is much higher than 12.5 and 25 microM, and for the extended treatment time, the concentration of 50 microM has more efficiency than 100 microM lactoferrin. To elucidate a mechanism involved in its antitumor effect, we studied the Akt cell signaling pathway of SGC-7901 while treated by 50 microM of lactoferrin after 0, 24, and 48 h, particularly Akt phosphorylation of 2 individual residues, Ser473 and Thr308, Akt/glycogen synthase kinase-3beta, forkhead in human rhabdomyosarcoma, and nuclear factor-kappaB proteins, respectively, activated by Western blot. The expressions of Akt, phosphorylated Akt Ser473, phosphorylated Akt Thr308, phosphorylated nuclear factor-kappa b p65 Ser536, and Bcl-2 significantly decreased; however, the expressions of phosphorylated glycogen synthase kinase-3beta Ser9, phosphorylated forkhead in human rhabdomyosarcoma Ser256, and phosphorylated caspase-9 Ser196 increased in response to lactoferrin treatment in SGC-7901. These results suggest that lactoferrin inhibits Akt activation and modulates its downstream proteins phosphorylation in apoptosis of SGC-7901 human stomach cancer cells.


Pin1 promotes histone H1 dephosphorylation and stabilizes its binding to chromatin.
Histone H1 plays a crucial role in stabilizing higher order chromatin structure. Transcriptional activation, DNA replication, and chromosome condensation all require changes in chromatin structure and are correlated with the phosphorylation of histone H1. In this study, we describe a novel interaction between Pin1, a phosphorylation-specific prolyl isomerase, and phosphorylated histone H1. A sub-stoichiometric amount of Pin1 stimulated the dephosphorylation of H1 in vitro and modulated the structure of the C-terminal domain of H1 in a phosphorylation-dependent manner. Depletion of Pin1 destabilized H1 binding to chromatin only when Pin1 binding sites on H1 were present. Pin1 recruitment and localized histone H1 phosphorylation were associated with transcriptional activation independent of RNA polymerase II. We thus identify a novel form of histone H1 regulation through phosphorylation-dependent proline isomerization, which has consequences on overall H1 phosphorylation levels and the stability of H1 binding to chromatin.


Management of Self-Injurious Behavior, Aggression, and Psychogenic Non-Epileptic Seizures in Patients With Tuberous Sclerosis: A Case Report With a Review of Literature.
Tuberous sclerosis complex (TSC) is a neurocutaneous disorder that affects multiple systems. TSC encompasses neurobehavioral abnormalities that are considered less sensitive and specific to the disease. Autism spectrum disorder, attention deficit disorder, anxiety, mood disorders, and self-injurious behavior (SIB) are neurobehavioral manifestations associated with tuberous sclerosis. Among them, SIB is poorly described and studied. We present a case report and a brief review of the literature, which offers us insight into the pathological mechanism that explains associated SIB in TSC patients and provides a possible multidisciplinary approach to handle this complicated association. The case details a 21-year-old female with tuberous sclerosis who went to the emergency department and then transfer to the psychiatric floor due to aggressive behavior and SIB. The patient had a history of infantile spasm in childhood and generalized tonic-clonic seizures (GTCS); the last episode was four years ago at the age of 17. During the hospital admission, the patient developed an apparent tonic-clonic seizure. Nevertheless, the electroencephalogram (EEG) shows no epileptiform pattern and because of the clinical presentation, it was concluded she had psychogenic nonepileptic seizures (PNES). The patient's CT scan showed a stable appearance of multiple calcified subependymal nodules and left frontal hypodensity. Mini-mental examination (MMSE) revealed mild cognitive impairment. Patients with TSC/SIB have higher frequencies of mental retardation, TSC2 mutations, history of infantile spasms, spike focus in the left frontal lobe. Also, TSC/SIB patients have a higher frequency of tubers in quadrants other than the left posterior neuroanatomical region in left occipital, parietal, and posterior temporal lobes. Our patient had four out of five of the risks factor for developing TSC/SIB. Almost all patients with tuberous sclerosis are expected to develop seizures. Nevertheless, our patient was seizure-free for two years and managed prophylactically with antiepileptic medication. PNES can also occur in patients with tuberous sclerosis. It is essential to be attentive to differentiate PNES from actual seizures due to their history of the high frequency of seizures in TSC. Given the multiple systems involved in the symptomatology of TSC, including the SIB and neurological concerns, multidisciplinary treatment strategies must be implemented. Treatment of TSC with SIB should include antiepileptic drugs covering seizures and managing the SIB's mood component. A neuroleptic could be added for patients who are difficult to manage.


Soil organic carbon and total nitrogen as affected by land use types in karst and non-karst areas of northwest Guangxi, China.
Human migration from the karst area to the non-karst area is an important approach for the restoration of degraded karst ecosystems. However, the effects of human-induced land-use change on soil properties are still unclear. The objective of this study was to investigate the effects of land use and parent material on soil organic carbon (SOC) and total nitrogen (TN) at a depth of 0-15 cm in karst and non-karst areas in southwest China. In the karst area, SOC and TN under different land uses decreased significantly in the order of secondary forestland > scrubland and abandoned farmland > farmland, commercial forestland and forage grassland. In the non-karst area, SOC and TN were the highest in scrubland and grassland, and were significantly higher than those in farmland and commercial forestland. Because of differences in parent material, SOC and TN were significantly higher in the karst area than those in the non-karst area. Abandoned farmland had the potential to increase SOC and TN significantly but land reclamation and cultivation had the opposite effect. SOC and TN were higher but cultivation-induced losses occurred more rapidly in calcareous soils than in red soils, indicating that more attention is needed for soil productivity and land use management in the karst area.


A quantitative risk assessment of West Nile virus introduction into Barbados.
To present a quantitative risk assessment of West Nile (WNV) virus introduction into Barbados, West Indies. Three possible modes were considered: a) WNV infected mosquitoes via air transport, by city of departure, b) WNV infected mosquitoes via marine transport and c) viraemic migratory, birds. We estimated the number of WNV infected migratory birds as the product of the proportion of migratory birds infected and the number of migratory birds entering Barbados in three taxonomic groups. We further estimated the number of days these birds would be infectious as: [formula: see text]. We then estimated the number (#) of infectious mosquito-days for mosquitoes entering Barbados via air transport as: # infected mosquitoes = (total flights per week/city) x (duration of WNV season) x (number of Culex mosquitoes aboard each flight) x (Culex mosquito WNV infection prevalence) x (vector competence index) x (days infectious). The number of infected mosquitoes entering Barbados via marine transport was estimated using a similar expression as for air transport, except that the number of airplanes and mosquitoes/airplane were substituted with the # of sea containers during a 22-week mosquito season and # of mosquitoes/container. Migratory birds (approximately 69-101 infected birds/year) were associated with the highest introductory risk followed by mode (a) (approximately 2 infected mosquitoes/year) and mode (b) (0. 004 infected mosquitoes/year). Migratory birds and mosquitoes via air are imminent threats for virus introduction. Impending co-circulation of West Nile virus and four strains of dengue virus may present new challenges for public health.


Chemiosmotic systems in bioenergetics: H(+)-cycles and Na(+)-cycles.
The development of membrane bioenergetic studies during the last 25 years has clearly demonstrated the validity of the Mitchellian chemiosmotic H+ cycle concept. The circulation of H+ ions was shown to couple respiration-dependent or light-dependent energy-releasing reactions to ATP formation and performance of other types of membrane-linked work in mitochondria, chloroplasts, some bacteria, tonoplasts, secretory granules and plant and fungal outer cell membranes. A concrete version of the direct chemiosmotic mechanism, in which H+ potential formation is a simple consequence of the chemistry of the energy-releasing reaction, is already proved for the photosynthetic reaction centre complexes. Recent progress in the studies on chemiosmotic systems has made it possible to extend the coupling-ion principle to an ion other than H+. It was found that, in certain bacteria, as well as in the outer membrane of the animal cell, Na+ effectively substitutes for H+ as the coupling ion (the chemiosmotic Na+ cycle). A precedent is set when the Na+ cycle appears to be the only mechanism of energy production in the bacterial cell. In the more typical case, however, the H+ and Na+ cycles coexist in one and the same membrane (bacteria) or in two different membranes of one and the same cell (animals). The sets of delta mu H+ and delta mu Na+ generators as well as delta mu H+ and delta mu Na+ consumers found in different types of biomembranes, are listed and discussed.


Angiotensin-converting enzyme inhibitor enhances liver regeneration following partial hepatectomy: involvement of bradykinin B2 and angiotensin AT1 receptors.
Angiotensin-converting enzyme (ACE) inhibitor enhances the liver regeneration in rats after partial hepatectomy (PH), though the precise mechanisms are unknown. To determine the roles of bradykinin and angiotensin II in the ACE inhibitor-induced enhancement of liver regeneration, we investigated effects of lisinopril (ACE inhibitor), candesartan and losartan (angiotensin II type 1 (AT1) receptor antagonists) and icatibant (bradykinin B2 receptor antagonist) on the hepatic regenerative response to 70% PH in the rat. The liver regeneration was evaluated by measuring the frequency of 5-bromo-2'-deoxyuridine (BrdU) incorporation into hepatocyte nuclei 48 h after PH. We found that administration of candesartan or losartan, as well as lisinopril, enhanced BrdU incorporation after PH, and the lisinopril-induced enhancement was inhibited in part (40%) by icatibant. PH induced the expression of hepatocyte growth factor (HGF) mRNA in remnant liver, and this PH-induced up-regulation of HGF mRNA was further enhanced not only by lisinopril but also by candesartan and losartan. Administration of icatibant inhibited up to 40% of the lisinopril-induced up-regulation of HGF mRNA. These results suggest that the blockade of the renin-angiotensin system by either ACE inhibitor or AT1 receptor antagonist enhances the hepatic regenerative response to PH, probably through an augmentation of hepatic HGF production. In addition to this mechanism, the activation of B2 receptors may also be involved in the ACE inhibitor-induced enhancement of hepatic regenerative response.


Association between normal or mildly reduced kidney function, cardiovascular risk and biomarkers for atherosclerosis: results from the ENCORE trial.
Moderate-to-severe kidney dysfunction is associated with atherosclerotic cardiovascular disease (ASCVD). Gradations of normal or mildly reduced kidney function may also associate with ASCVD risk. We conducted a secondary analysis using baseline data from the Exercise and Nutritional Interventions for Cardiovascular Health (ENCORE) trial. Participants were sedentary, overweight and obese adults with unmedicated pre-hypertension or Stage I hypertension and an estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2. The Pooled Cohorts Equations were used to estimate a 10-year risk for first ASCVD event. Carotid artery intima-media thickness (IMT) and brachial artery flow-mediated dilation (FMD) were measured to assess subclinical atherosclerosis and vascular endothelial function, respectively. Using linear regression, we examined the association between eGFR and ASCVD risk, IMT and FMD. Participants (N = 139) were predominantly women (65%), white (60%), with a mean age of 52.0 ± 9.6 years and mean eGFR of 89.1 ± 15.0 mL/min/1.73 m2. Lower eGFR of 15 mL/min/1.73 m2 was associated with higher ASCVD risk [b = -2.7% (95% confidence interval: -3.7, -1.8%), P < 0.001], higher IMT [b = 0.05 mm (0.03, 0.08 mm), P < 0.001] and lower FMD [b = -0.87% (-1.64, -0.11%), P = 0.026]. Compared with eGFR ≥90 mL/min/1.73 m2, those with eGFR 60-89 mL/min/1.73 m2 had higher mean ASCVD risk (7.6% versus 2.7%; P < 0.001), greater mean IMT (0.74 mm versus 0.66 mm; P < 0.001) and lower mean FMD (2.0% versus 3.7%; P = 0.026). After controlling for CVD risk factors, the association between eGFR and IMT remained significant (P < 0.001), and eGFR and FMD trended toward significance (P = 0.08). Among overweight and obese adults with unmedicated high blood pressure and eGFR ≥60 mL/min/1.73 m2, lower eGFR is associated with a greater 10-year risk for first ASCVD event, higher IMT and relatively impaired FMD.


Efficacy of a local anesthetic pain pump in abdominoplasty.
Recently, pain infusion pumps for postoperative pain control have gained popularity in many surgical specialties. This investigation was designed to evaluate the efficacy of a local anesthetic pain infusion pump in management of postoperative pain in abdominoplasty patients. A retrospective study of 38 abdominoplasty patients with local anesthetic pain pumps and 35 abdominoplasty patients without pain pumps was performed. Pain pumps were loaded with 0.25% or 0.5% bupivacaine and infused at a constant rate of 4 ml/hour. All patients were admitted postoperatively and started on a narcotic patient-controlled analgesia. Postoperative patient-controlled analgesia narcotic use and pain scores were recorded every 2 hours by the nursing staff. For the first 24 hours of postoperative hospital stay, pain medication, pain scores, and antiemetic use were determined from the patients' charts. Hospital stay was also reviewed. In the pain pump group, there was a small but not statistically significant reduction in pain medication use (2.65 versus 3.04 pain units) (p = 0.34). Interestingly, pain scores were higher in the pain pump group but not significantly (2.73 versus 2.31) (p = 0.17). There was no statistically significant difference in the use of antiemetics (0.8 versus 0.6) (p = 0.60). Hospital length of stay averaged 2.2 days in the pain pump group and 2.5 days in the group without pain pumps (p = 0.09). The postoperative use of pain pumps in abdominoplasty patients does not significantly improve pain management. Further investigation into this application of the pain pump is necessary before recommending their routine use in abdominoplasty patients.


Gene expression profile analysis of tobacco leaf trichomes.
Leaf trichomes of Nicotiana tabacum are distinguished by their large size, high density, and superior secretion ability. They contribute to plant defense response against biotic and abiotic stress, and also influence leaf aroma and smoke flavor. However, there is limited genomic information about trichomes of this non-model plant species. We have characterized Nicotiana tabacum leaf trichome gene expression using two approaches. In the first, a trichome cDNA library was randomly sequenced, and 2831 unique genes were obtained. The most highly abundant transcript was ribulose bisphosphate carboxylase (RuBisCO). Among the related sequences, most encoded enzymes involved in primary metabolism. Secondary metabolism related genes, such as isoprenoid and flavonoid biosynthesis-related, were also identified. In the second approach, a cDNA microarray prepared from these 2831 clones was used to compare gene expression levels in trichome and leaf. There were 438 differentially expressed genes between trichome and leaves-minus-trichomes. Of these, 207 highly expressed genes in tobacco trichomes were enriched in second metabolic processes, defense responses, and the metabolism regulation categories. The expression of selected unigenes was confirmed by semi-quantitative RT-PCR analysis, some of which were specifically expressed in trichomes. The expression feature of leaf trichomes in Nicotiana tabacum indicates their metabolic activity and potential importance in stress resistance. Sequences predominantly expressed in trichomes will facilitate gene-mining and metabolism control of plant trichome.


Oral health status of chinese paediatric and adolescent oncology patients with chemotherapy in Hong Kong: a pilot study.
To study the oral health status of Chinese children and adolescents undergoing chemotherapy in Hong Kong. All Chinese children and adolescent oncology patients aged 18 or below attending the Children's Centre for Cancer and Blood Disease at a hospital for chemotherapy were invited and parental consent was sought before they were accepted into the study. The study comprised of 1) a parental questionnaire, 2) the collection of medical history and 3) a clinical examination for tooth decay (caries) and mucosal status. A total of 69 patients were invited, and they all participated in this study. Their mean age was 9.2±5.0 and 44 (64%) were males. Twenty-six patients (38%) had no caries experience (DMFT and/or dmft = 0). Higher caries experience was detected in participants that were not born in Hong Kong, had completed active chemotherapy, participated in school dental care service and whose parents had low educational levels. There were 41 patients with active chemotherapy, 24 of whom were diagnosed with acute leukaemia, 5 with haematological malignancies other than leukaemia and 11 with solid tumours. Antimetabolites, cytotoxic antibiotics, alkylating agents and plant alkaloids were administered in 49%, 32%, 24% and 22% of them, respectively. Twenty-six (63%) patients showed no mucosal complications. The most common oral complication was oral mucositis (24%) followed by petechiae (10%). About two-thirds of paediatric and adolescent cancer patients had caries experience, which was more common among those who had completed chemotherapy. Oral mucositis followed by petechiae were the two most common complications of receiving chemotherapy.


Could Cratylia argentea replace Tifton 85 hay on growing and finishing lamb diets in tropical areas?
Legumes shrubs such as Cratylia argentea have an ability to thrive in environments with low water availability and poor soil. On the other hand, forage grasses such as Tifton 85 have a greater demand for inputs to be productive. The objective of this study was to evaluate the performance of growing and finishing Lacaune lambs fed Cratylia argentea hay as an alternative to Tifton 85 (Cynodon spp). Twenty-four Lacaune lambs aged between five and six months (average body weight [BW] 21.50 ± 3.38 kg) were arranged in a split-plot randomized block design. The plots consisted of different Cratylia to Tifton 85 hay proportions (0, 20%, 40%, or 100%, dry matter [DM] basis) as a roughage replacement in the total diet. The subplots represented two evaluation times, entitled "initial period" and "final period", which consisted of the early seven days of total feces and urine collection, and the last seven days of the experiment, respectively. The lambs were blocked by weight with six replicates per treatment. The results show that the level of Tifton 85 replacement for Cratylia hay in the roughage portion of the lamb diet did not influence (P > 0.05) weight gain (WG), dry matter intake or dry matter digestibility; feed conversion, feed efficiency; and the evaluated nitrogen balance variables. The digestibility coefficient of neutral detergent fiber decreased linearly as Tifton 85 replacement for Cratylia level was increased, which probably happened due to the presence of highly lignified material within the Cratylia hay. However, the alternative legume maintained animal performance of Tifton 85. In conclusion, Cratylia hay can be recommended as a potential substitute for Tifton 85 hay, which requires greater inputs for the production. Cratylia may be considered a feeding strategy for livestock production, especially for smallholder livestock systems and regions with unfavorable soil and climate.


Thoracolaparoscopic-Assisted Esophagectomy for Corrosive-Induced Esophageal Stricture.
Corrosive-induced stricture of the digestive tract is a dreaded complication following corrosive ingestion. When surgical reconstruction is needed, esophagectomy helps to avoid the long-term complications related to leaving behind the scarred native esophagus. We tried to ascertain the feasibility and safety of a thoracolaparoscopic-assisted esophagectomy in such a setting. A 32-year-old male presented with corrosive-induced esophageal stricture that lead to progressive dysphagia not amenable for endoscopic dilatation. Thoracoscopic approach was used for mobilization of the scarred esophagus under vision. Laparoscopic approach was used in mobilizing the stomach and creating a conduit. Esophagogastric anastomosis was performed in the neck. The patient had an uneventful recovery postoperatively and was discharged after six days on a semisolid diet. Thoracolaparoscopic-assisted esophagectomy can be safely performed for corrosive strictures of the esophagus. Besides improving the ease of performing the procedure, it also helps mitigate the morbidity associated with conventional open surgery in such cases.


Cloning and expression of Mycobacterium bovis BCG DNA in "Streptomyces lividans".
The ability of "Streptomyces lividans" to use the expression signals of genes from Mycobacterium bovis BCG was tested in vivo by using gene fusions. Random DNA fragments from M. bovis BCG were inserted into promoter-probe plasmids in Escherichia coli and in "S. lividans." Comparison with promoter activity detected with random DNA fragments from the respective hosts suggested that "S. lividans" efficiently utilizes a high proportion of mycobacterial promoters, whereas a smaller fraction are expressed, and expressed more weakly, in E. coli. M. bovis BCG DNA fragments were also inserted into the specially constructed translational fusion vector (pIJ688) in "S. lividans." pIJ688 contains the kanamycin phosphotransferase gene (neo) from transposon Tn5, truncated at its amino terminus, as the indicator. The results suggested that "S. lividans" uses M. bovis BCG translational signals almost as efficiently as its own signals. Moreover, several hybrid proteins with an M. bovis BCG-derived amino terminus seemed to be reasonably stable in "S. lividans." These experiments indicate that "S. lividans" may be a suitable host for the expression of Mycobacterium leprae and Mycobacterium tuberculosis genes from their own signals. This is a precondition for the expression of entire biosynthetic pathways, which could be valuable in the production of diagnostic and therapeutic agents. The vectors may also have wider applications for the analysis of gene expression in Streptomyces.


TIMP-1 promotes VEGF-induced neovascularization in the retina.
Proteolysis of vascular basement membranes and surrounding extracellular matrix is a critical early step in neovascularization. It requires alteration of the balance between matrix metalloproteinases (MMPs) and proteins that bind to and inactivate MMPs, tissue inhibitors of metalloproteinases (TIMPs). TIMP-1 has been demonstrated to inhibit neovascularization in chick chorioallantoic membranes. However, TIMP-1 has also been shown to either promote or inhibit cell proliferation and migration in different settings. To determine whether genetic alteration of the MMP/TIMP-1 ratio would alter retinal neovascularization, we crossed mice that express vascular endothelial growth factor (VEGF) in photoreceptors with TIMP-1-deficient mice or mice that overexpress TIMP-1. Compared to VEGF transgene-positive/TIMP-1-sufficient mice, VEGF transgene-positive/TIMP-1-deficient mice showed smaller neovascular lesions. There was also no difference between the two groups of mice in the appearance of the neovascularization by light or electron microscopy. Compound VEGF/TIMP-1 transgenic mice had increased expression of both VEGF and TIMP-1 in the retina, and had more neovascularization than mice that had increased expression of VEGF alone. These gain- and loss-of-function data suggest that alteration of the TIMP-1/MMP ratio modulates retinal neovascularization in a complex manner and not simply by altering the proteolytic activity and thereby invasiveness of endothelial cells.


The rationality of informal argumentation: a Bayesian approach to reasoning fallacies.
Classical informal reasoning "fallacies," for example, begging the question or arguing from ignorance, while ubiquitous in everyday argumentation, have been subject to little systematic investigation in cognitive psychology. In this article it is argued that these "fallacies" provide a rich taxonomy of argument forms that can be differentially strong, dependent on their content. A Bayesian theory of content-dependent argument strength is presented. Possible psychological mechanisms are identified. Experiments are presented investigating whether people's judgments of the strength of 3 fallacies--the argumentum ad ignorantiam, the circular argument or petitio principii, and the slippery slope argument--are affected by the factors a Bayesian account predicts. This research suggests that Bayesian accounts of reasoning can be extended to the more general human activity of argumentation.


Patient and hospital delays in acute ischaemic stroke in a Dublin teaching hospital.
A limiting factor for thrombolysis in ischaemic stroke is delayed presentation to hospital. Prolonged A&E stay and delayed rehabilitation affects care. We evaluated the delay in presentation, A&E stay and rehabilitation delivery in 117 consecutive stroke patients. The mean presentation delay was 16.0 +/- 23.7 hours. A prior history of TIA or stroke, a reduced Glascow Coma Scale and larger strokes were associated with shorter delays to presentation. Longer delays occurred in patients living alone. The mean time spent in A&E was 11 hours, those with larger strokes spent shorter time. There were significant delays in referral to, and assessment by certain rehabilitation disciplines. Delayed presentation in stroke is a barrier to thrombolysis. Increasing public awareness may reduce this delay. In addition, prolonged A&E stay and delayed rehabilitation may adversely affect management, outcome and duration of hospital stay. Further study is required to investigate the reasons and possible solutions for such deficiencies.


Open issues in transcatheter aortic valve implantation. Part 1: patient selection and treatment strategy for transcatheter aortic valve implantation.
An exponential increase in the use of transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis has been witnessed over the recent years. The current article reviews different areas of uncertainty related to patient selection. The use and limitations of risk scores are addressed, followed by an extensive discussion on the value of three-dimensional imaging for prosthesis sizing and the assessment of complex valve anatomy such as degenerated bicuspid valves. The uncertainty about valvular stenosis severity in patients with a mismatch between the transvalvular gradient and the aortic valve area, and how integrated use of echocardiography and computed tomographic imaging may help, is also addressed. Finally, patients referred for TAVI may have concomitant mitral regurgitation and/or coronary artery disease and the management of these patients is discussed.


Evaluation of gross and microscopic hematuria.
In summary, hematuria, either gross or microscopic and with or without any accompanying symptoms, should always alert the clinician to the possibility of serious urologic disease and should virtually always trigger a thorough urologic investigation. This can be done by immediate referral to the urologist, or it can be done by the primary care physician initiating the diagnostic work-up in children by obtaining studies for acute poststreptococcal glomerulonephritis and in adults by obtaining excretory urograms with physiologic voiding films and also by urine cytologic studies and urine cultures. Appropriate referral to a urologist can then be made for additional studies that might be indicated, such as cystoscopy and cystourethroscopy and for meticulous follow-up of any abnormal findings. The physician who delays or defers a careful investigation into the cause of a given patient's hematuria (gross or microscopic) does the patient a disservice at best and, at worst, may inadvertently permit a significant disease process to become more extensive.


Synthesis and characterisation of silver nanoparticles using leaf extract of Artemisia afra and their in vitro antimicrobial and antioxidant activities.
In this study, the conversion of silver ions into ∼30.74 nm sized silver nanoparticles (AgNPs) was achieved in 30 min at a reaction temperature of 80-90°C in aqueous leaf extract of Artemisia afra. The synthesised AgNPs showed surface plasmon resonance in the range of 423-438 nm. Spherical and face-centred cubic nanoparticles were confirmed by transmission electron microscope (TEM) and X-ray diffraction (XRD) analysis, respectively. Fourier transform infra-red (FTIR) results indicated that the obtained nanoparticles were stabilised and capped through the carbonyl and carboxylate ion groups possibly from flavonoids, terpenoids, phenolics and esters content of the extracts. In addition, the AgNPs were assessed for their biological potentials against some microbes and, also, their free radical scavenging ability was established. The AgNPs exhibited interesting antimicrobial and antioxidant properties better than the aqueous extract of A. afra.


Radiographic and clinical outcomes in one- and two-level transforaminal lumbar interbody fusions: a comparison of bullet versus banana cages.
The aim of this study was to determine whether cage morphology influences clinical and radiographic outcomes following short-segment transforaminal lumbar interbody fusion (TLIF) procedures. The authors retrospectively reviewed one- and two-level TLIFs at a single tertiary care center between August 2012 and November 2019 with a minimum 1-year radiographic and clinical follow-up. Two cohorts were compared based on interbody cage morphology: steerable "banana" cage or straight "bullet" cage. Patient-reported outcome measures (PROMs), radiographs, and complications were analyzed. A total of 135 patients with 177 interbody levels were identified; 45 patients had 52 straight cages and 90 patients had 125 steerable cages. Segmental lordosis increased with steerable cages, while it decreased with straight cages (+3.8 ± 4.6 vs -1.9 ± 4.3, p < 0.001). Conversely, the mean segmental lordosis of adjacent lumbar levels decreased in the former group, while it increased in the latter group (-0.52 ± 1.9 vs +0.52 ± 2.1, p = 0.004). This reciprocal relationship results in global sagittal parameters, including pelvic incidence minus lumbar lordosis and lumbar distribution index, which did not change after surgery with either cage morphology. Multivariate analysis confirmed that steerable cage morphology, anterior cage positioning, and less preoperative index-level segmental lordosis were associated with greater improvement in index-level segmental lordosis. PROMs were improved after surgery with both cage types, and the degree of improvement did not differ between cohorts (p > 0.05). Perioperative and radiographic complications were similar between cohorts (p > 0.05). Overall reoperation rates, as well as reoperation rates for adjacent-segment disease within 2 years of surgery, were not significantly different between cohorts. Steerable cages are more likely to lie within the anterior disc space, thus increasing index-level segmental lordosis, which is accompanied by a reciprocal change in segmental alignment at the adjacent lumbar levels. The converse relationship occurs for straight cages, with a kyphotic change at the index levels and reciprocal lordosis occurring at adjacent levels.


Novel serotonin type 3 receptor partial agonists for the potential treatment of irritable bowel syndrome.
Serotonin type 3 (5-HT(3)) receptor partial agonists are being targeted as potential new drugs for the treatment of irritable bowel syndrome (IBS). Two new chemical series bearing indazole and indole cores have exhibited nanomolar binding affinity for the h5-HT(3)A receptor. A range of partial agonist activities in HEK cells heterologously expressing the h5-HT(3)A receptor were measured for the indazole series. Excellent 5-HT(3) receptor selectivity, favorable in vitro metabolic stability and CYP inhibition properties, and good oral in vivo potency in the murine von Bezold-Jarisch reflex model is exemplified thereby indicating the series to have potential utility as improved IBS agents.


Non-collinear high harmonic generation: a promising outcoupling method for cavity-assisted XUV generation.
We present first experimental results of our investigation of non-collinear high harmonic generation (NCHHG) with a chirped pulse amplification system. Collimated high harmonic radiation of higher than 9th order is observed along the bisector of two fundamental beams crossing in a xenon gas target. The obtained results show that cavity-assisted non-collinear high harmonic generation is a promising candidate for efficient generation and outcoupling of extreme ultraviolet (XUV) radiation.


10(-10) temporal contrast for femtosecond ultraintense lasers by cross-polarized wave generation.
We take advantage of nonlinear properties associated with chi(3) tensor elements in BaF2 cubic crystal to improve the temporal contrast of femtosecond laser pulses. The technique presented is based on cross-polarized wave (XPW) generation. We have obtained a transmission efficiency of 10% and 10(-10) contrast with an input pulse in the millijoule range. This filter does not affect the spectral shape or the phase of the cleaned pulse. It also acts as an efficient spatial filter. In this method the contrast enhancement is limited only by the extinction ratio of the polarization discrimination device.


The wire anchor loop traction (WALT) maneuver.
Crossing the neck of large complex intracranial aneurysms for the purposes of stent deployment can be challenging using standard over the wire techniques. We describe a novel yet simple technique for straightening out the loop formed within a large intracranial aneurysm, which is often required in order to cross the aneurysm neck into the distal branch. Both the microcatheter and microwire are initially introduced into the distal vasculature, followed by withdrawal of the microwire to a point parallel to the distal exiting branch. The microcatheter and microwire are then gently withdrawn and a series of maneuvers to gradually reduce the loop is performed, obviating the need for distal purchase in the form of a stent, balloon, or coil, which have previously been described to maintain distal purchase.


Limitations in estimating gluconeogenesis and Cori cycling from mass isotopomer distributions using [U-13C6]glucose.
Tayek and Katz proposed calculating gluconeogenesis's contributions to glucose production and Cori cycling from mass isotopomer distributions in blood glucose and lactate during [U-13C6]glucose infusion [Tayek, J. A., and J. Katz. Am. J. Physiol. 272 (Endocrinol. Metab. 35): E476-E484, 1997]. However, isotopic exchange was not adequately differentiated from dilution, nor was condensation of labeled with unlabeled triose phosphates properly equated. We introduce and apply corrected equations to data from subjects fasted for 12 and 60 h. Impossibly low contributions of gluconeogenesis to glucose production at 60 h are obtained (23-41%). Distributions in overnight-fasted normal subjects calculate to only approximately 18%. Cori cycling estimates are approximately 10-15% after overnight fasting and 20% after 60 h of fasting. There are several possible reasons for the underestimates. The contribution of gluconeogenesis is underestimated because glucose production from glycerol and amino acids not metabolized via pyruvate is ascribed to glycogenolysis. Labeled oxaloacetate and alpha-ketoglutarate can exchange during equilibrium with circulating unlabeled aspartate, glutamate, and glutamine. Also, the assumption that isotopomer distributions in arterial lactate and hepatic pyruvate are the same may not be fulfilled.


The early progenitors of mouse dendritic cells and plasmacytoid predendritic cells are within the bone marrow hemopoietic precursors expressing Flt3.
Flt3 ligand (Flt3L) is a growth factor for hemopoietic progenitors and can promote the expansion of both conventional dendritic cells (DCs) and plasmacytoid predendritic cells (p-preDCs). The cells responding to Flt3L treatment and the precursors for the DCs and p-preDCs had not been fully characterized. We examined different mouse bone marrow (BM) hemopoietic precursor populations for the surface expression of Flt3 and tested them for early DC and p-preDC precursor activity. Most DC precursor activity, other than that given by multipotent hemopoietic stem cells, was within the downstream precursors expressing Flt3. The majority of mouse BM common lymphoid precursors expressed high levels of Flt3 and these were the most efficient precursors of both DCs and p-preDCs. In contrast, only a small proportion of the common myeloid precursors (CMPs) expressed Flt3, but the precursor activity for both DCs and p-preDCs was within this minor Flt3+ CMP fraction. The granulocyte and macrophage precursors and pro-B cells did not express Flt3 and had no DC or p-preDC precursor activity. These findings demonstrate that the early precursors for all DC subtypes are within the BM Flt3+ precursor populations, regardless of their lymphoid or myeloid lineage orientation.


Staphylococcus aureus Infects Osteoclasts and Replicates Intracellularly.
Osteomyelitis (OM), or inflammation of bone tissue, occurs most frequently as a result of bacterial infection and severely perturbs bone structure. OM is predominantly caused by Staphylococcus aureus, and even with proper treatment, OM has a high rate of recurrence and chronicity. While S. aureus has been shown to infect osteoblasts, it remains unclear whether osteoclasts (OCs) are also a target of intracellular infection. Here, we demonstrate the ability of S. aureus to intracellularly infect and divide within OCs. OCs were differentiated from bone marrow macrophages (BMMs) by exposure to receptor activator of nuclear factor kappa-B ligand (RANKL). By utilizing an intracellular survival assay and flow cytometry, we found that at 18 h postinfection the intracellular burden of S. aureus increased dramatically in cells with at least 2 days of RANKL exposure, while the bacterial burden decreased in BMMs. To further explore the signals downstream of RANKL, we manipulated factors controlling OC differentiation, NFATc1 and alternative NF-κB, and found that intracellular bacterial growth correlates with NFATc1 levels in RANKL-treated cells. Confocal and time-lapse microscopy in mature OCs showed a range of intracellular infection that correlated inversely with S. aureus-phagolysosome colocalization. The propensity of OCs to become infected, paired with their diminished bactericidal capacity compared to BMMs, could promote OM progression by allowing S. aureus to evade initial immune regulation and proliferate at the periphery of lesions where OCs are most abundant.IMPORTANCE The inflammation of bone tissue is called osteomyelitis, and most cases are caused by an infection with the bacterium Staphylococcus aureus To date, the bone-building cells, osteoblasts, have been implicated in the progression of these infections, but not much is known about how the bone-resorbing cells, osteoclasts, participate. In this study, we show that S. aureus can infect osteoclasts and proliferate inside these cells, whereas bone-residing macrophages, immune cells related to osteoclasts, destroy the bacteria. These findings elucidate a unique role for osteoclasts to harbor bacteria during infection, providing a possible mechanism by which bacteria could evade destruction by the immune system.