A system for checking radiation therapy calculations for treatment time or monitor setting.
Errors in the calculation of radiation therapy treatment time or monitor setting are likely to occur with regularity unless adequate quality control procedures are utilized. These errors can be greatly reduced if appropriate computer systems are employed with programs which utilize analytical representations of dosimetric quantities. A system wherein dosimetry technologists routinely check treatment calculations using a computer terminal has been in operation in our department for several years and has proved helpful in uncovering calculation errors.


Does HIV status make a difference in the experience of lifetime abuse? Descriptions of lifetime abuse and its context among low-income urban women.
Women living in poor urban communities are doubly disadvantaged with regard to increased risk for two major public health crises in the United States today--HIV/AIDS (human immunodeficiency virus/acquired immunodeficiency syndrome) and violence. This study moves beyond the comparison of rates of lifetime abuse among women to incorporate contextual information of the abusive situation and experiences of HIV-positive women and a sample of sociodemographically similar HIV-negative women. A total of 611 women, 310 of whom were diagnosed as HIV positive, provided interviews integrating quantitative data and qualitative text on their lifetime experience of abuse. Quantitative results yielded few statistically significant differences between the lifetime experiences of violence between HIV-positive women and their HIV-negative counterparts. Of the women, 62% reported intimate partner violence, and 38% reported experiencing nonpartner abuse as an adult. A majority of the abused women reported that their alcohol or drug use or their partner's alcohol or drug use was associated with the abuse experienced. Significant differences were found between HIV-positive women and HIV-negative women in the pattern of abuse experienced as a child, the frequency of abuse as an adult, and the involvement of women's drinking before or during a violent episode. Qualitative excerpts from the interviews were found to differ thematically and were integrated with the quantitative data to provide a more comprehensive understanding of the women's contextual situation in understanding interpersonal violence experienced by both HIV-positive and HIV-negative women.


[Cytogenetics. Science and people].
Some little-known facts are presented about foundation of the Institute of Cytology, Academy of Sciences of the USSR (now of Russia). The advancement of main lines investigation in the field of cytogenetics, carried out at the Institute from its inception up to now, has been traced, with special attention being called to organization of a scientific school of cytogenetics.


Microsurgical Vascular Manipulation in Aneurysm Surgery and Delayed Ischemic Injury.
The role of aggressive surgical manipulation with clot evacuation, arachnoid dissection, and papaverine-guided adventitial dissection of large vessels during ruptured aneurysm surgery in reducing vasospasm is controversial. Here we describe a single-institution experience in aneurysm surgery outcomes with and without aggressive surgery. We performed retrospective analysis of all patients >18 years of age with subarachnoid hemorrhage (SAH) from anterior circulation aneurysms between 2008 and 2013 at the University of New Mexico Hospital. Vasospasm was characterized on days 3 through 14 after SAH based on: (1) angiography, (2) vasospasm requiring angiographic intervention, (3) development of delayed ischemic neurologic deficit (DIND), and (4) radiological appearance of new strokes. Of 159 patients, 114 (71.6%) had "aggressive" and 45 (28.3%) had standard microsurgery. More than 60% of patients presented with a Hunt and Hess score of ≥3 and a Fisher grade (FG) of 4. Compared with standard surgery, there was a statistically significant decrease in the incidence of DIND in patients undergoing aggressive surgery (18.4% vs 37.8%, p=0.01). Moreover, there was a reduction in the number of new strokes by 30% in the aggressive surgery group with moderate or higher degrees of vasospasm (46.0% vs 76.5%, p=0.06). In the same group with FG 4 SAH, however, this difference was more than 50% (30% vs 64.7%, p=0.02). We conclude that aggressive surgical manipulation during aneurysm surgery results in lower incidence of DIND and new strokes. This effect is most pronounced in patients with FG 4 SAH.


Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study.
'Acute-on-chronic liver failure' (ACLF) is characterised in a more advanced stage by liver failure associated with multiple other end-organ failure. The global clinical characteristics of this entity remain, however, ill-defined. To characterise and evaluate the clinicopathological features of patients with ACLF compared with patients with chronic decompensated cirrhosis (CHD) in a prospective, homogeneous cohort of patients with histologically proven alcoholic cirrhosis from 2002 to 2007. In total 250 patients were screened (ACLF (n=70, 28%) and CHD (n=180, 72%)). Alcoholic liver disease was observed in respectively 61/70 (87%) of patients with ACLF and 72/180 (40%) of patients with CHD. After exclusion of 31 patients, 102 patients were studied: 54 with ACLF (median age 51 years; Child-Pugh 12±2; in-hospital mortality 46% (25/54)) and 48 patients with CHD (median age 53 years; Child-Pugh 10±2; in-hospital mortality 10% (5/48)). In the patients with ACLF who survived the hospital stay, the difference in transplant-free survival compared with patients with CHD tended to attenuate with time. At admission the apparent infection of patient groups was comparable but during hospitalisation infection occurred more frequently in patients with ACLF (31/53 (58%)) than in those with CHD (12/47=26%) (p=0.007). Early signs of infection, positive systemic inflammatory response syndrome (SIRS) criteria at admission and ductular bilirubinostasis (p=0.04), were early features that predicted outcome in ACLF. Patients with ACLF have a high short-term mortality but those who survived the acute exacerbation show a long-term outcome comparable to that of patients with CHD. Infection is the most common cause of mortality in these patients. Positive SIRS criteria and ductular bilirubinostasis are early markers of ACLF and might allow more rapid identification of high-risk patients.


Matching faces for semantic information and names: an event-related brain potentials study.
In face identification, it has been controversial whether or not access to biographical information and to a person's name are mediated by qualitatively different loci. We recorded ERPs while participants saw two successive faces and performed a matching task that either required retrieval of semantic information ("same or different profession?"), or retrieval of the person's name ("same or different number of forename syllables?"). For both tasks, slow ERP activity between the first and the second face was characterized by a prominent right posterior negativity, with the asymmetry being larger for the name than the semantic matching task. ERPs to the second face showed a difference between congruent (matching) and incongruent (mismatching) trials, with more negative ERPs for incongruent trials. In the semantic matching task, these differences were significant between 450 and 550 ms, and resembled an N400, with a maximum negativity over the vertex. In the name matching task, the topography of this congruency effect was qualitatively different from that seen in semantic matching. These findings suggest that different brain substrates mediate the access to semantic and name information.


Reconstruction of protein networks from an atlas of maize seed proteotypes.
A comprehensive knowledge of proteomic states is essential for understanding biological systems. Using mass spectrometry, we mapped an atlas of developing maize seed proteotypes comprising 14,165 proteins and 18,405 phosphopeptides (from 4,511 proteins), quantified across eight tissues. We found that many of the most abundant proteins are not associated with detectable levels of their mRNAs, and we provide evidence for three potential explanations: transport of proteins between tissues; diurnal, out-of-phase accumulation of mRNAs and cognate proteins; and differential lifetimes of mRNAs compared with proteins. Likewise, many of the most abundant mRNAs were not associated with detectable levels of their proteins. Across the entire dataset, protein abundance was poorly correlated with mRNA levels and was largely independent of phosphorylation status. Comparisons between proteotypes revealed the quantitative contribution of specific proteins and phosphorylation events to the spatially and temporally regulated starch and oil biosynthetic pathways. Reconstruction of signaling networks established associations of proteins and phosphoproteins with distinct biological processes acting during seed development. Additionally, a protein kinase substrate network was reconstructed, enabling the identification of 762 potential substrates of specific protein kinases. Finally, examination of 694 transcription factors revealed remarkable constraints on patterns of expression and phosphorylation within transcription factor families. These results provide a resource for understanding seed development in a crop that is the foundation of modern agriculture.


Propranolol in acute myocardial infarction: the MILIS experience.
The results of the propranolol limb of the Multicenter Investigation of the Limitation of Infarct Size are reviewed. A total of 269 patients, who presented with symptoms and electrocardiographic signs suggesting acute myocardial infarction were randomized to acute intravenous and subsequent oral therapy with propranolol (n = 134) or placebo (n = 135). Eligibility for acute beta-blocker therapy was determined on the basis of readily available, noninvasive tests. Therapy was started at an average time of 8.5 hours after onset of symptoms. The full induction dose of intravenous propranolol (0.1 mg/kg) was tolerated by 90% of treated patients, and oral maintenance therapy was being continued in 82% of treated patients on the second hospital day. There was a significant reduction in heart rate throughout maintenance therapy with propranolol, which continued through the tenth hospital day. There was no significant difference in the incidence of congestive heart failure between propranolol- and placebo-treated groups. There was also no significant difference between the 2 groups in infarct size estimated by measurement of serum CK-MB, planimetry of infarct area on technetium pyrophosphate myocardial scintigrams or R-wave measurements in patients with transmural anterior and inferior infarcts. There was no significant difference in mortality between the 2 groups during an average of 36 months' follow-up. Although propranolol can be administered safely to patients with acute myocardial infarction who are selected on the basis of simple clinical criteria, there is no evidence of reduction of infarct size when beta blockade is begun 8.5 hours after the onset of symptoms.


Microvascular architecture of the fetal cotyledons in water buffaloes (Bubalus bubalis) during different stages of pregnancy.
To elucidate the morphological background of physiological differences between bovine and buffalo gestation forty-two placentae ranging from the 3rd to 10th month of pregnancy were used to study the microvascular architecture of the fetal cotyledons in the buffalo. The tissues were prepared for light and scanning electron microscopy by paraformaldehyde fixation and corrosion casting of the fetal cotyledonary vascular system. Histology and vascular casts revealed the buffalo fetal cotyledons to consist of a series of conical villous trees changing from a wide to slender shape during pregnancy, and with a base strictly facing the fetal side. The branches of these trees, intermediate and terminal villi, projected radially from the stem, thus representing a rough type of villous tree. A second type of tree lacked these branches and was therefore termed smooth villus. The rough type was most prevalent, and the intermediate and terminal villi showed capillary complexes arranged in stories by the 4th to 5th month of gestation. The stories became broader and denser with the progress of pregnancy (6th to 7th month of gestation), due to extensive growth of new capillaries and simultaneous development of convolutions causing the vascular ridges of the terminal villi to appear bushy. Near term (9th to 10th month) the capillary system became very dense, particularly at the margin of the vascular ridges, leaving only narrow spaces for the corresponding maternal septal tissue. In detail, at its base the trunk of each villous tree contained a single central stem artery which originated from the allantochorionic arterial system, and 1-3 parallel peripheral stem veins. When approaching the cone tip, these vessels branched into new stem arteries and veins, each giving rise to arterioles and venules according to the principle vascularization of the stem villus first, followed by intermediate and terminal villi. The capillary complex of the terminal villi consisted of arterial capillary limbs, capillary loops with sinusoidal dilatations and anastomoses, and venous capillary limbs. The latter converged into venules of terminal and intermediate villi which joined stem veins leading into allantochorionic veins. In conclusion, the fetal vasculature of the buffalo placentome was greatly increased from early pregnancy to near term. This was denoted by the general development of stem villous trees and an increase in the volume and density of the capillary system of the terminal villi, reflecting the increasing need of materno-fetal substance exchange in the buffalo placenta, particularly near term.


Obesity, proinflammatory mediators, adipose tissue progenitors, and breast cancer.
There is emerging evidence that obesity is associated with an increase in the incidence, severity, and mortality from different types of cancer, including postmenopausal breast cancer. Here, we discuss the role of white adipose tissue (WAT) cells and of related soluble factors in the local and metastatic growth of this neoplastic disease. Moreover, we discuss the recent increase in the use of WAT-derived progenitor cells in breast cancer patients to enhance the quality of breast reconstruction and the related risks. In several murine models, WAT cells and progenitors were found to have cooperative roles in promoting local breast cancer. Moreover, they were found to contribute to adipocytes and pericytes supporting the cancer vasculature, and stimulated the metastatic progression of breast cancer. There are some clinically retrospective data showing a significant increase in the frequency of intraepithelial neoplasia in patients who received a lipofilling procedure for breast reconstruction compared with controls. Preclinical models and clinical studies are urgently needed to investigate how to inhibit the tumor-promoting activity of WAT cells and progenitors. The risks associated with the use of WAT cells for breast reconstructions should be better investigated retrospectively and prospectively.


Recent Advances in Application of Alkoxy Radical in Organic Synthesis.
Alkoxy radicals have been identified as versatile intermediates in synthetic chemistry in the last few decades. Over the last decade, various catalytic processes for the in situ generation of alkoxy radicals have been explored, leading to the development of new synthetic methodologies based on alkoxy radicals. In this review, we provided a comprehensive review of recent developments in the utilization of alkoxy radicals in diverse organic transformations, natural product synthesis, and the late-stage modification of bioactive molecules through the implementation of the photoredox methodology.


Melanin optical properties provide evidence for chemical and structural disorder in vivo.
Melanin is a ubiquitous chromophore of human skin but its in vivo optical properties are relatively unexplored. We present here a detailed study of the optical absorption of melanin present in melanocytic nevi of human subjects with Fitzpatrick skin type III. Using diffuse reflectance spectroscopy, we show that the melanin absorption spectrum exhibits an exponential dependence on wavelength in vivo with a decay constant that follows a normal distribution, characteristic of a random biological variable. This is the first time such direct in vivo quantitative evidence is obtained supporting the recently proposed hypothesis of chemical and structural disorder for melanin. In addition, the ability to measure the melanin optical properties in vivo opens new ways for the study of melanin in its native environment as well as for the non-invasive study and characterization of various skin disorders and diseases.


Mechanisms underlying the protective effect of zinc and selenium against cadmium-induced oxidative stress in zebrafish Danio rerio.
The present study was designed to elucidate the protective effect mechanism of Zinc (Zn) and Selenium (Se) on cadmium (Cd)-induced oxidative stress in zebrafish. For this purpose we investigate the response of oxidative stress markers, metallothionein accumulation and gene expression in liver and ovary of female zebrafish exposed to 0,4 mg/l Cd in water and supplemented with Zn (5 mg kg(-1)) and/or Se (2 mg kg(-1)) for 21 days in their diet. Liver and ovary Cd uptake was evaluated after the exposure period. Cd exposure significantly inhibited the antioxidant enzyme activities termed as catalase (CAT), superoxide dismutase (SOD) and glutathione peroxydase (GPx) and caused a pronounced malondialdehyde (MDA) accumulation in both organs. Co-administration of Zn and Se reversed the Cd-induced toxicity in liver and ovary measured as MDA accumulation. Interestingly, gene expression patterns of Cat, CuZnSod and Gpx were up-regulated when related enzymatic activities were altered. Zebrafish metallothionein transcripts (zMt) significantly decreased in tissues of fish supplemented with Zn and/or Se when compared to Cd-exposed fish. Our data would suggest that Zn and Se protective mechanism against Cd-induced oxidative stress is more depending on the correction of the proteins biological activities rather than on the transcriptional level of related genes.


The effect of implementing cognitive load theory-based design principles in virtual reality simulation training of surgical skills: a randomized controlled trial.
Cognitive overload can inhibit learning, and cognitive load theory-based instructional design principles can be used to optimize learning situations. This study aims to investigate the effect of implementing cognitive load theory-based design principles in virtual reality simulation training of mastoidectomy. Eighteen novice medical students received 1 h of self-directed virtual reality simulation training of the mastoidectomy procedure randomized for standard instructions (control) or cognitive load theory-based instructions with a worked example followed by a problem completion exercise (intervention). Participants then completed two post-training virtual procedures for assessment and comparison. Cognitive load during the post-training procedures was estimated by reaction time testing on an integrated secondary task. Final-product analysis by two blinded expert raters was used to assess the virtual mastoidectomy performances. Participants in the intervention group had a significantly increased cognitive load during the post-training procedures compared with the control group (52 vs. 41 %, p = 0.02). This was also reflected in the final-product performance: the intervention group had a significantly lower final-product score than the control group (13.0 vs. 15.4, p < 0.005). Initial instruction using worked examples followed by a problem completion exercise did not reduce the cognitive load or improve the performance of the following procedures in novices. Increased cognitive load when part tasks needed to be integrated in the post-training procedures could be a possible explanation for this. Other instructional designs and methods are needed to lower the cognitive load and improve the performance in virtual reality surgical simulation training of novices.


Green tea drinking and multigenetic index on the risk of stomach cancer in a Chinese population.
The purpose of our study was to examine the roles of green tea drinking, other risk and protective factors, and polymorphism of susceptibility genes such as GSTM1, GSTT1, GSTP1, and p53 codon 72 and their possible joint effects on the risk of stomach cancer. A population-based case-control study was conducted in Taixing, China, including 206 newly diagnosed cases with stomach cancer and 415 healthy control subjects. Epidemiological data were collected by in-person interviews using a standard questionnaire. Polymorphisms of susceptibility genes were assayed by PCR-RFLP techniques. A multigenetic index was created by summing up the number of risk genotypes. The data were analyzed using the logistic regression model. A reverse association between green tea drinking and risk of stomach cancer was observed with an adjusted odds ratio (OR) of 0.59 (95% confidence interval [CI] = 0.34-1.01). Dose-response relationship was shown (p-trend < 0.05). A higher score on the multigenetic index was associated with increased risk of stomach cancer with an adjusted OR of 2.21 (95% CI = 1.02-4.79) for those with at least 3 risk genotypes compared to those with <2 risk genotypes. Green tea drinking was suggested to have more than multiplicative interactions with alcohol consumption with an adjusted OR for interaction of 4.57 (95% CI = 1.62-12.89), and with higher multigenetic index with adjusted OR for interaction of 2.31 (95% CI = 0.88-6.03). The protective effect of green tea drinking was observed on the risk of stomach cancer and the possible effect modification by susceptibility genes was suggested.


An integrated platform approach enables discovery of potent, selective and ligand-competitive cyclic peptides targeting the GIP receptor.
In any drug discovery effort, the identification of hits for further optimisation is of crucial importance. For peptide therapeutics, display technologies such as mRNA display have emerged as powerful methodologies to identify these desired de novo hit ligands against targets of interest. The diverse peptide libraries are genetically encoded in these technologies, allowing for next-generation sequencing to be used to efficiently identify the binding ligands. Despite the vast datasets that can be generated, current downstream methodologies, however, are limited by low throughput validation processes, including hit prioritisation, peptide synthesis, biochemical and biophysical assays. In this work we report a highly efficient strategy that combines bioinformatic analysis with state-of-the-art high throughput peptide synthesis to identify nanomolar cyclic peptide (CP) ligands of the human glucose-dependent insulinotropic peptide receptor (hGIP-R). Furthermore, our workflow is able to discriminate between functional and remote binding non-functional ligands. Efficient structure-activity relationship analysis (SAR) combined with advanced in silico structural studies allow deduction of a thorough and holistic binding model which informs further chemical optimisation, including efficient half-life extension. We report the identification and design of the first de novo, GIP-competitive, incretin receptor family-selective CPs, which exhibit an in vivo half-life up to 10.7 h in rats. The workflow should be generally applicable to any selection target, improving and accelerating hit identification, validation, characterisation, and prioritisation for therapeutic development.


Independent ambulators with high sacral myelomeningocele: the relation between walking kinematics and energy consumption.
The aims of this study were to determine the relation between gait kinematics (center of mass excursions) and measures of oxygen consumption and oxygen cost. Fourteen independent ambulating children with myelomeningocele (nine females, five males; mean age 8 years 7 months) and thirteen children with no history of neuromuscular disorder were evaluated. At their comfortable walking speed all patients exhibited oxygen cost and oxygen consumption values that exceeded the normal level by more than 1 SD. Pelvic obliquity demonstrated the strongest relation with oxygen cost which suggests that ultimately hip abductor strength may play a key role in energy demands during gait. Despite the exaggerated pelvic kinematics, vertical and horizontal center of mass excursions of the trunk and whole-body during the gait cycle were not significantly greater than normal (p>0.05). Decreased self-selected walking velocity at which many of these children consider comfortable and stable may be predicated on an optimal center of mass movement that approximates the magnitude observed in normal gait. The slower walking velocity decreases walking efficiency. Conversely, the increased center of mass movement that would accompany a faster gait would probably impose intolerable oxygen consumption levels. Strengthening programs that focus on the gluteus medius and maximus to decrease compensatory trunk and pelvic motions, allowing the patients to adopt a faster gait without exacerbating kinematic and center of mass motions and which enabled more efficient walking hold promise for these patients.


Conventional analysis of trial-by-trial adaptation is biased: Empirical and theoretical support using a Bayesian estimator.
Research on human motor adaptation has often focused on how people adapt to self-generated or externally-influenced errors. Trial-by-trial adaptation is a person's response to self-generated errors. Externally-influenced errors applied as catch-trial perturbations are used to calculate a person's perturbation adaptation rate. Although these adaptation rates are sometimes compared to one another, we show through simulation and empirical data that the two metrics are distinct. We demonstrate that the trial-by-trial adaptation rate, often calculated as a coefficient in a linear regression, is biased under typical conditions. We tested 12 able-bodied subjects moving a cursor on a screen using a computer mouse. Statistically different adaptation rates arise when sub-sets of trials from different phases of learning are analyzed from within a sequence of movement results. We propose a new approach to identify when a person's learning has stabilized in order to identify steady-state movement trials from which to calculate a more reliable trial-by-trial adaptation rate. Using a Bayesian model of human movement, we show that this analysis approach is more consistent and provides a more confident estimate than alternative approaches. Constraining analyses to steady-state conditions will allow researchers to better decouple the multiple concurrent learning processes that occur while a person makes goal-directed movements. Streamlining this analysis may help broaden the impact of motor adaptation studies, perhaps even enhancing their clinical usefulness.


Grade B pancreatic fistulas do not affect survival after pancreatectomy for pancreatic cancer: A multicenter observational study.
Several studies have demonstrated that postoperative complications after pancreatectomy for pancreatic cancer adversely affect survival. The impact on survival of a pancreatic fistula according to the classification of the International Study Group for Pancreatic Surgery has not been fully evaluated. The aim of this multicenter, observational study was to evaluate the impact of pancreatic fistula on pancreatic cancer patients who had undergone pancreatectomy. Between 2001 and 2012, 1,397 patients who underwent pancreatectomy for pancreatic cancer at 7 high-volume centers in Japan were reviewed retrospectively. The impact of pancreatic fistula on survival was evaluated by univariate and multivariate analysis. Pancreatic fistula occurred in 327 of 1,397 patients (23.4%) and was classified based on the International Study Group for Pancreatic Surgery as follows: grade A in 9.9%, grade B in 10.6%, and grade C in 2.9% of the patients. Median survival time in no fistula/grade A, grade B, and grade C were 23.6, 26.0, and 9.0 months, respectively. There was no significant difference in overall survival between patients with no fistula/grade A and those with grade B (P = .403); in contrast, overall survival in patients with grade C was worse than in patients without grade C (P < .001). The multivariate Cox proportional hazard analysis demonstrated that grade C pancreatic fistula was an independent prognostic factor (hazard ratio 1.59; 95% confidence interval, 1.03-2.45; P = .035). Grade B pancreatic fistula after pancreatectomy does not adversely affect long-term survival, but a grade C pancreatic fistula has a negative impact on long-term survival of patients with pancreatic cancer.


[Therapeutic readthrough strategy for suppression of nonsense mutations in duchenne muscular dystrophy].
Effective treatment for Duchenne muscular dystrophy (DMD) is currently unavailable. Readthrough of disease-causing premature termination codons might alleviate the symptoms of genetic diseases caused by nonsense mutations. Several ribosome-binding compounds, including selective antibiotics and synthetic novel small molecules, induce translational readthrough, restoring full-length functional proteins. Here in this innovative therapeutic strategy has been summarized with a focus on DMD. We have previously reported that negamycin restored dystrophin expression with less toxicity than gentamicin in mdx mice. To explore more potent readthrough inducers, we established the transgenic mouse called READ (readthrough evaluation and assessment by dural receptor) for readthrough-specific detection. Using READ mice, we discovered drug candidates, including sterically negamycin-like small molecules and aminoglycoside derivatives. The newly developed small molecules induced dose-dependent readthrough with greater potency than ataluren in vitro and promoted the expression of dystrophin and reduction in serum creatine kinase activity in mdx mice. Moreover, the aminoglycoside derivative restored both dystrophin protein and contractile function of mdx skeletal muscles with appreciably higher readthrough activity and lower toxicity than that of gentamicin. Furthermore, we confirmed the efficacy of a thioglycolate-based depilatory agent to enhance the topical delivery of skin-impermeable drugs, including aminoglycosides. These promising new chemotherapeutic agents with beneficial effects on readthrough action, lower toxicity, and transdermal delivery may have significant value in treating or preventing genetic diseases caused by nonsense mutations.


A pan-cancer analysis of TNFAIP8L1 in human tumors.
TNFAIP8L1, as a recently identified member in TNFAIP8 family, plays an important role in tumorigenesis. However, a pan-cancer analysis of TNFAIP8L1 in human tumors has not been conducted until now. The main purpose of study is to investigate TNFAIP8L1 during 33 different types of human tumors by using TCGA and GTEx. The pan-cancer analysis showed that TNFAIP8L1 was significantly over-expressed in 15 cancers and low-expressed in 9 cancers. There were distinct relations between TNFAIP8L1 expression and prognosis of patients with cancer. Furthermore, we also found that DNA methylation and RNA modification of TNFAIP8L1 were associated with many cancers. And then, we detected that TNFAIP8L1 level was positively associated with cancer-associated fibroblasts (CAFs) in many tumors. And, we obtained that TNFAIP8L1 expression was related with most of immune inhibitory and stimulatory genes in multiple types of tumors. We also found TNFAIP8L1 expression was correlated with most of chemokine, receptor, MHC, immunoinhibitor and immunostimulator gens in most of cancers. Moreover, we detected TNFAIP8L1 expression was associated with TMB and MSI in several tumors. Finally, TNFAIP8L1 gene had a significant positive association with 5 genes including BCL6B, DLL4, PCDH12, COL4A1 and DLL4 in the majority of tumors. GO enrichment and KEGG pathway analyses showed that TNFAIP8L1 in thepathogenesis of cancer may be related to "purine nucleoside binding," "purine ribonucleoside binding," "ECM-receptor interaction," etc. Our first pan-cancer study may provide a deep comprehending of TNFAIP8L1 in tumoeigenesis from different tumors.


[The complement-activating action of modern x-ray contrast agents].
The study conducted proved that triombrast (dose dependently) > hexabrics > Ultravist > or = melitrast = omnipac in a concentration interval of 0.03-30.0 mg iodine/ml in vitro and in a dose interval of 0.5-2.0 g iodine/kg in vivo activate the complement system (CS) according to the alternative way in the blood of "sensitive" rats. The degree of CS activation by radiopaque agents (ROA) is significantly determined mathematically by their viscosity and relation of the number of iodine atoms to the number of ions or dissolved particles, and by their hydrophilic (for nonion CS) and osmotic (for ion monomeric CS) properties.


Radical model of arsenic(III) toxicity: theoretical and EPR spin trapping studies.
Arsenic is one of the most environmentally significant pollutants and a great global health concern. Although a growing body of evidence suggests that reactive oxygen species (ROS) mediate the mechanism of arsenic toxicity, the exact mechanism remains elusive. In this study, we examine the capacity of trivalent arsenic species arsenous acid (iAs(III)), monomethylarsonous acid (MMA(III)), and dimethylarsinous acid (DMA(III)) to generate ROS through a theoretical analysis of their structures, redox properties, and their reactivities to various ROS using a density functional theory (DFT) approach at the B3LYP/6-31+G**//B3LYP/6-31G* level of theory and by employing electron paramagnetic resonance (EPR) spin trapping studies using 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) as a spin trap. Results show that the oxidized forms (As(IV)) are structurally more stable compared to the reduced forms (As(II)) that impart elongated As-O bonds leading to the formation of As(III) and hydroxide anion. Enthalpies of one-electron reduction and oxidation indicate that increasing the degree of methylation makes it harder for As(III) to be reduced but easier to be oxidized. The order of increasing favorability for arsenical activation by ROS is O2 < O2(•-) < HO(•), and the oxidation of DMA(III) to DMA(V) is highly exoergic in multiple redox pathways with concomitant generation of radicals. This is followed by MMA(III) and by iAs(III) being the least favorable. Spin trapping studies showed a higher propensity for methylated arsenicals to generate radicals than iAs(III) upon treatment with H2O2. However, in the presence of Fe(II,III), all showed radical generation where MMA(III) gave predominantly C-centered adducts, while acidified iAs (III) and DMA(III) gave primarily HO-adducts, and their formation was affected in the presence of SOD suggesting a As(III)-OO/OOH radical intermediate. Therefore, our results suggest a basis for the increased redox activity of methylated arsenicals that can be applied to the observed trends in arsenic methylation and toxicity in biological systems.


Discrete Survival Time Constructions for Studying Marital Formation and Dissolution in Rural South Africa.
Introduction: Marriage formation and dissolution are important life-course events which impact psychological well-being and health of adults and children experiencing the events. Family studies have usually concentrated on analyzing single transitions including Never Married to Married and Married to Divorced. This does not allow understanding and interrogation of dynamics of these life changing events and their effects on individuals and their families. The objective of this study was to assess determinants associated with transitions between and within marital states in South Africa. Methods: The population-based data available for this study consists of over 55, 000 subjects representing over 340, 000 person-years exposure from the Africa Health Research Institute (AHRI) in rural KwaZulu-Natal, South Africa. It was collected from 1 January 2004 to 31 December 2016. Multilevel multinomial, binary and competing risks regression models were used to model marital state occupation, transitions between marital states as well as investigate determinants of marital dissolution, respectively. Results: Between the years 2006 and 2007, a subject was more likely to be married than never married when compared to years 2004 - 2005. After 2007, subjects were less likely to be married than never married and the trend reduced over the years up to 2016 [with OR=0.86, CI=(0.78; 0.94), OR=0.71, CI=(0.64; 0.78), OR=0.60, CI=(0.54; 0.67), OR=0.50, CI=(0.44; 0.56), and OR = 0.43, CI = (0.38; 0.48)] for periods 2008 - 2009, 2010 - 2011, 2012 - 2013, 2014 - 2015, and 2016, respectively. In 2008 - 2009, subjects were more likely to experience a marital dissolution than in the period 2004 - 2005 and the trend slightly reduces from 2010 until 2013 [OR=24.49, CI=(5.53; 108.37)]. Raising age at first sexual debut was found to be inversely associated with a marital dissolution [OR = 0.97;CI = (0.95; 0.99)]. Highly educated subjects were more likely to stay in one marital state than those who never went to school [OR=6.43, CI=(4.89; 8.47), OR=18.86, CI=(1.14; 53.31), and OR=2.96, CI=(1.96; 4.46) for being married, separated and widowed, respectively, among subjects with tertiary education]. As the age at first marriage increased, subjects became less likely to experience a marital separation [OR = 0.06, CI = (0.00; 1.11), OR = 0.05, CI = (0.00; 0.91), and OR = 0.04, CI = (0.00; 0.76) for subjects who entered a first marriage at ages 18 - 22, 23 - 29, and 30 - 40, respectively]. Conclusion: The study found that marrying at later ages is associated with a lower rate of marital dissolution while more educated subjects tend to stay longer in one marital state. Sexual debut at later ages was associated with a lower likelihood of experiencing a marital dissolution. There could, however, be some factors that are not accounted for in the model that may lead to heterogeneity in these dynamics in our model specification which are captured by the random effects in the model. Nonetheless, we may postulate that existing programs that encourage delay in onset of sexual activity for HIV risk reduction for example, may also have a positive impact on lowering rates of marital dissolution, thus ultimately improving psychological and physical health.


[Features of coarse calico damage by hollow-point bullets of ammunitions to a 12-gauge fire smoothbore weapon (12×70) under the conditions of remote shooting distance].
The article presents the experimental study results of damaged clothes imitators' (coarse calico) features in consequence of shot by ammunitions with hollow-point bullet from a 12-gauge fire smoothbore weapon (12×70). The generation mechanism of coarse calico damage during wound of underlying biological human body's imitator by bullet and the factors influencing on mentioned process have been clarified using high-speed video recording.


Role of CrkII in Fcgamma receptor-mediated phagocytosis.
Phagocytosis of IgG-opsonized pathogens by Fcgamma receptors requires extensive remodeling of the actin cytoskeleton, a process regulated by the small GTPase Rac. Vav was thought to be the guanine nucleotide exchange factor responsible for the activation of Rac, but recent evidence indicates that Fcgamma receptor-mediated phagocytosis is unaffected in macrophages lacking all three isoforms of Vav. We therefore tested whether another GEF, DOCK180, participates in Fcgamma receptor-initiated phagocytosis. DOCK180 associates with the adaptor protein Crk, which mediates recruitment of the GEF to sites of tyrosine phosphorylation. CrkII and DOCK180 were found to accumulate at the phagocytic cup. Knockdown of Crk or DOCK180 in murine macrophages using small interfering RNA inhibited phagocytosis of IgG-opsonized particles. Moreover, transfection of dominant negative CrkII prevented both recruitment of DOCK180 and the activation of Rac at the phagocytic cup. This is the first report of a role for either Crk or DOCK180 in Fcgamma receptor-mediated phagocytosis. The Crk-DOCK180 complex is involved in the clearance of apoptotic cells, which unlike the ingestion of IgG-opsonized particles, is an anti-inflammatory process. The finding that CrkII-DOCK180 is also responsible, at least in part, for the effects of Fcgamma receptors implies that additional, parallel pathways must account for the associated pro-inflammatory effect.


Exhaustively Characterizing a Patient Cohort by Prevalence of EMR Facts: a Generalized, Vendor-Agnostic Method for Quality Control and Research.
We present a method for rapidly ranking all distinct facts in an electronic medical record (EMR) system by howover-represented or under-represented they are in a patient cohort of interest relative to some larger referencepopulation of patients in the same EMR. We have implemented this method as a plugin for i2b2, the open sourcedata warehouse platform widely used in research health informatics. Our method is highly flexible in terms of whatmedical terminologies it supports and is vendor-independent thanks to leveraging the i2b2 star schema rather thanany one specific EMR. It can be applied to a wide range of informatics problems including finding healthdisparities, searching for variables to include in a risk calculator or computable phenotype, detection ofcomorbidities, discovery of adverse drug reactions. The case study we present here uses this software to findunlabeled flowsheets for patients suffering from amyotrophic lateral sclerosis.


Vasculotide, an Angiopoietin-1 mimetic, reduces acute skin ionizing radiation damage in a preclinical mouse model.
Most cancer patients are treated with radiotherapy, but the treatment can also damage the surrounding normal tissue. Acute skin damage from cancer radiotherapy diminishes patients' quality of life, yet effective biological interventions for this damage are lacking. Protecting microvascular endothelial cells from irradiation-induced perturbations is emerging as a targeted damage-reduction strategy. Since Angiopoetin-1 signaling through the Tie2 receptor on endothelial cells opposes microvascular perturbations in other disease contexts, we used a preclinical Angiopoietin-1 mimic called Vasculotide to investigate its effect on skin radiation toxicity using a preclinical model. Athymic mice were treated intraperitoneally with saline or Vasculotide and their flank skin was irradiated with a single large dose of ionizing radiation. Acute cutaneous damage and wound healing were evaluated by clinical skin grading, histology and immunostaining. Diffuse reflectance optical spectroscopy, myeloperoxidase-dependent bioluminescence imaging of neutrophils and a serum cytokine array were used to assess inflammation. Microvascular endothelial cell response to radiation was tested with in vitro clonogenic and Matrigel tubule formation assays. Tumour xenograft growth delay experiments were also performed. Appreciable differences between treatment groups were assessed mainly using parametric and non-parametric statistical tests comparing areas under curves, followed by post-hoc comparisons. In vivo, different schedules of Vasculotide treatment reduced the size of the irradiation-induced wound. Although skin damage scores remained similar on individual days, Vasculotide administered post irradiation resulted in less skin damage overall. Vasculotide alleviated irradiation-induced inflammation in the form of reduced levels of oxygenated hemoglobin, myeloperoxidase bioluminescence and chemokine MIP-2. Surprisingly, Vasculotide-treated animals also had higher microvascular endothelial cell density in wound granulation tissue. In vitro, Vasculotide enhanced the survival and function of irradiated endothelial cells. Vasculotide administration reduces acute skin radiation damage in mice, and may do so by affecting several biological processes. This radiation protection approach may have clinical impact for cancer radiotherapy patients by reducing the severity of their acute skin radiation damage.


Adaptation of mineral trioxide aggregate to dentine walls compared with other root-end filling materials: A systematic review.
This systematic review analysed the literature comparing marginal adaptation of mineral trioxide aggregate (MTA) with other filling materials in root-end cavities. The PubMed, Ovid, Web of Science, SCOPUS, and Cochrane library databases were searched using appropriate keywords related to root-end filling materials and adaptation. Of 38 articles assessed, 20 met the inclusion criteria. No in vivo study was identified. In 10 studies, MTA gave the best marginal adaptation results, but no significant differences were found between MTA and any of the tested filling materials in seven studies. There was great variability in the study designs including analysed surface, unit of gap measurement and magnification amount during analysis. On the basis of available evidence, MTA presented good marginal adaptation to dentine walls. This review identified the need for the development of standardised methods to evaluate the adaptation property of root-end filling materials in ex vivo studies as well as in clinical studies evaluating outcome.


Early psychosis and aggression: predictors and prevalence of violent behaviour amongst individuals with early onset psychosis.
Studies in the area of psychosis and violence to date suggest that those who suffer from psychosis are at higher risk for perpetration of such aggressive behaviours. In fact, it has been suggested that variables such as substance use and personality may mediate this relationship. Other variables, such as childhood physical abuse, might also be implicated in the etiology. In the current study, a sample of one hundred and eighteen participants with a primary diagnosis of psychosis were interviewed and prevalence rates for aggressive experiences were as follows: history of trouble with the law (45%), history of emotional abuse (9.6%), physical abuse (38.8%), and sexual abuse (60.2%). With regard to perpetration, 69.6% reported verbal or physical aggression (69.6%), and further, 61% reported problems with substances. Logistic regression procedures were used with a number of the variables under study and relationships were evidenced between psychopathy scores, history of abuse, and regular drug use. History of child abuse was related to violence history, with those who were victims of child abuse being more likely to be violent in later life. In addition higher scores on the psychopathy measure were linked with violence history. This study was a first step towards identifying persons suffering from a mental illness who may be at risk for violence by identifying who, among first episode clients, may be more likely to perpetrate violent behaviours. Targeted interventions and strategies may be further refined so that individuals receiving mental health services may be better served.


The Confluence of Innovation in Therapeutics and Regulation: Recent CMC Considerations.
The field of human therapeutics has expanded tremendously from small molecules to complex biological modalities, and this trend has accelerated in the last two decades with a greater diversity in the types and applications of novel modalities, accompanied by increasing sophistication in drug delivery technology. These innovations have led to a corresponding increase in the number of therapies seeking regulatory approval, and as the industry continues to evolve regulations will need to adapt to the ever-changing landscape. The growth in this field thus represents a challenge for regulatory authorities as well as for sponsors. This review provides a brief description of novel biologics, including innovative antibody therapeutics, genetic modification technologies, new developments in vaccines, and multifunctional modalities. It also describes a few pertinent drug delivery mechanisms such as nanoparticles, liposomes, coformulation, recombinant human hyaluronidase for subcutaneous delivery, pulmonary delivery, and 3D printing. In addition, it provides an overview of the current CMC regulatory challenges and discusses potential methods of accelerating regulatory mechanisms for more efficient approvals. Finally, we look at the future of biotherapeutics and emphasize the need to bring these modalities to the forefront of patient care from a global perspective as effectively as possible.


Quantification of Uncertainty in Peptide-MHC Binding Prediction Improves High-Affinity Peptide Selection for Therapeutic Design.
The computational identification of peptides that can bind the major histocompatibility complex (MHC) with high affinity is an essential step in developing personal immunotherapies and vaccines. We introduce PUFFIN, a deep residual network-based computational approach that quantifies uncertainty in peptide-MHC affinity prediction that arises from observational noise and the lack of relevant training examples. With PUFFIN's uncertainty metrics, we define binding likelihood, the probability a peptide binds to a given MHC allele at a specified affinity threshold. Compared to affinity point estimates, we find that binding likelihood correlates better with the observed affinity and reduces false positives in high-affinity peptide design. When applied to examine an existing peptide vaccine, PUFFIN identifies an alternative vaccine formulation with higher binding likelihood. PUFFIN is freely available for download at http://github.com/gifford-lab/PUFFIN.


Iron-based superparamagnetic nanoparticle contrast agents for MRI of infection and inflammation.
OBJECTIVE. In this article, we summarize the progress to date on the use of superparamagnetic iron oxide nanoparticles (SPIONs) as contrast agents for MRI of inflammatory processes. CONCLUSION. Phagocytosis by macrophages of injected SPIONs results in a prolonged shortening of both T2 and T2* leading to hypointensity of macrophage-infiltrated tissues in contrast-enhanced MR images. SPIONs as contrast agents are therefore useful for the in vivo MRI detection of macrophage infiltration, and there is substantial research and clinical interest in the use of SPION-based contrast agents for MRI of infection and inflammation. This technique has been used to identify active infection in patients with septic arthritis and osteomyelitis; importantly, the MRI signal intensity of the tissue has been found to return to its unenhanced value on successful treatment of the infection. In SPION contrast-enhanced MRI of vascular inflammation, animal studies have shown decreased macrophage uptake in atherosclerotic plaques after treatment with statin drugs. Human studies have shown that both coronary and carotid plaques that take up SPIONs are more prone to rupture and that abdominal aneurysms with increased SPION uptake are more likely to grow. Studies of patients with multiple sclerosis suggest that MRI using SPIONs may have increased sensitivity over gadolinium for plaque detection. Finally, SPIONs have enabled the tracking and imaging of transplanted stem cells in a recipient host.


Expression of human telomerase reverse transcriptase mediates the senescence of mesenchymal stem cells through the PI3K/AKT signaling pathway.
Multipotent mesenchymal stem cells (MSCs) are widely used as seed cells in studies of tissue engineering and regenerative medicine; however, their clinical application is limited due to replicative senescence. It has been demonstrated that telomerase expression extends the lifespan and maintains the bone-forming ability of MSCs; however, the detailed role and the underlying molecular mechanisms in MSCs remain largely unknown. In the present study, we found that senescence was associated with human telomerase reverse transcriptase (hTERT) expression, and telomere length and telomerase activity. We established a short interfering RNA (siRNA) targeting hTERT and a gene expression vector carrying hTERT and transfected these into the MSCs to investigate the detailed role and the underlying molecular mechanisms of action of hTERT in MSCs. We found that the downregulation of hTERT by siRNA markedly decreased telomere length and telomerase activity in the MSCs, whereas the overexpression of hTERT increased telomere length and telomerase activity in the MSCs. The downregulation of hTERT inhibited cell proliferation and promoted the senescence and apoptosis of MSCs, whereas the upregulation of hTERT increased cell proliferation and decreased the senescence and apoptosis of MSCs. Of note, we also found that the activation of the PI3K/AKT signaling pathway was mediated by hTERT and that blocking this pathway using LY294002 inhibited hTERT expression, induced senescence and decreased the proliferation of MSCs. These findings reveal a previously unknown regulatory mechanism of hTERT, indicating that hTERT mediates the senescence of MSCs through the PI3K/AKT signaling pathway.


Investigating Effects of Tulathromycin Metaphylaxis on the Fecal Resistome and Microbiome of Commercial Feedlot Cattle Early in the Feeding Period.
The objective was to examine effects of treating commercial beef feedlot cattle with therapeutic doses of tulathromycin, a macrolide antimicrobial drug, on changes in the fecal resistome and microbiome using shotgun metagenomic sequencing. Two pens of cattle were used, with all cattle in one pen receiving metaphylaxis treatment (800 mg subcutaneous tulathromycin) at arrival to the feedlot, and all cattle in the other pen remaining unexposed to parenteral antibiotics throughout the study period. Fecal samples were collected from 15 selected cattle in each group just prior to treatment (Day 1), and again 11 days later (Day 11). Shotgun sequencing was performed on isolated metagenomic DNA, and reads were aligned to a resistance and a taxonomic database to identify alignments to antimicrobial resistance (AMR) gene accessions and microbiome content. Overall, we identified AMR genes accessions encompassing 9 classes of AMR drugs and encoding 24 unique AMR mechanisms. Statistical analysis was used to identify differences in the resistome and microbiome between the untreated and treated groups at both timepoints, as well as over time. Based on composition and ordination analyses, the resistome and microbiome were not significantly different between the two groups on Day 1 or on Day 11. However, both the resistome and microbiome changed significantly between these two sampling dates. These results indicate that the transition into the feedlot-and associated changes in diet, geography, conspecific exposure, and environment-may exert a greater influence over the fecal resistome and microbiome of feedlot cattle than common metaphylactic antimicrobial drug treatment.


Characteristics of Benign Paroxysmal Positional Vertigo Following an Earthquake.
Benign Paroxysmal Positional Vertigo (BPPV) is a commonly encountered peripheral vestibular disorder. People exposed to massive earthquakes experience intense and long-term problem associated with dizziness. The purpose of our study is to investigate this relationship and to demonstrate the efficacy of the treatment modalities used in the management of patients with post-earthquake dizziness. The study was carried out by examining the retrospective records of patients who presented with dizziness to the otorhinolaryngological outpatient unit before and after the Elazig earthquake that occurred on 24th Jan 2020. Parameters evaluated include patients' age and gender, onset of dizziness, accompanying symptoms and comorbidities, videonystagmography (VNG) findings, pre- and post-treatment Visual Analogue Scale (VAS), Dizziness Handicap Inventory (DHI), and Hospital Anxiety and Depression Scale (HADS). The number of patients who presented with dizziness to our outpatient clinic after the earthquake and were included in our study totaled 84. The number of patients who visited the outpatient clinic before the earthquake was identified to be 75. In the earthquake related group, while there was a statistically significant difference between residual symptoms (RS) and the need for repetitive repositioning maneuvers, there was no statistically significant difference detected for age, gender, and comorbidities. Also, no statistically significant difference was found in the pre- and post-treatment assessments of VAS, DHI, and HADS median values in the earthquake group. There was a remarkable increase in the number of patients presenting with dizziness in the early post-earthquake period. Management of these patients may differ from the classic BPPV. Residual symptoms appearing after performing repositioning maneuvers can be more commonly seen among these patients.


Coronary heart disease is associated with regional grey matter volume loss: implications for cognitive function and behaviour.
Coronary heart disease (CHD) has been associated with impaired cognition, but the mechanisms underlying these changes remain unclear. We designed this study to determine whether adults with CHD show regional brain losses of grey matter volume relative to controls. We used statistical parametric mapping (SPM5) to determine regional changes in grey matter volume of T(1)-weighted magnetic resonance images of 11 adults with prior history of myocardial infarction relative to seven healthy controls. All analyses were adjusted for total grey and white matter volume, age, sex and handedness. CHD participants showed a loss of grey matter volume in the left medial frontal lobe (including the cingulate), precentral and postcentral cortex, right temporal lobe and left middle temporal gyrus, and left precuneus and posterior cingulate. CHD is associated with loss of grey matter in various brain regions, including some that play a significant role in cognitive function and behaviour. The underlying causes of these regional brain changes remain to be determined.


Application of X-Y separable 2-D array beamforming for increased frame rate and energy efficiency in handheld devices.
Two-dimensional arrays present significant beamforming computational challenges because of their high channel count and data rate. These challenges are even more stringent when incorporating a 2-D transducer array into a battery-powered hand-held device, placing significant demands on power efficiency. Previous work in sonar and ultrasound indicates that 2-D array beamforming can be decomposed into two separable line-array beamforming operations. This has been used in conjunction with frequency-domain phase-based focusing to achieve fast volume imaging. In this paper, we analyze the imaging and computational performance of approximate near-field separable beamforming for high-quality delay-and-sum (DAS) beamforming and for a low-cost, phase-rotation-only beamforming method known as direct-sampled in-phase quadrature (DSIQ) beamforming. We show that when high-quality time-delay interpolation is used, separable DAS focusing introduces no noticeable imaging degradation under practical conditions. Similar results for DSIQ focusing are observed. In addition, a slight modification to the DSIQ focusing method greatly increases imaging contrast, making it comparable to that of DAS, despite having a wider main lobe and higher side lobes resulting from the limitations of phase-only time-delay interpolation. Compared with non-separable 2-D imaging, up to a 20-fold increase in frame rate is possible with the separable method. When implemented on a smart-phone-oriented processor to focus data from a 60 x 60 channel array using a 40 x 40 aperture, the frame rate per C-mode volume slice increases from 16 to 255 Hz for DAS, and from 11 to 193 Hz for DSIQ. Energy usage per frame is similarly reduced from 75 to 4.8 mJ/ frame for DAS, and from 107 to 6.3 mJ/frame for DSIQ. We also show that the separable method outperforms 2-D FFT-based focusing by a factor of 1.64 at these data sizes. This data indicates that with the optimal design choices, separable 2-D beamforming can significantly improve frame rate and battery life for hand-held devices with 2-D arrays.


Physician office-based information systems for managed care plans.
Three problems must be overcome before an ideal information system can be implemented. First, such setups are costly. For a group of 7 to 10 physicians, the price will be upwards of $100,000. Physicians must therefore weigh this cost against the direct economic benefit of personnel savings and the indirect benefit of enhanced information accuracy. Second, the culture of the organization must be assessed and found to be supportive before implementing any of these recommendations. If the information system is to function optimally, physicians must be willing to participate in the data entry. Some entry functions are no more onerous than filling out a superbill. Other tasks, such as completion of referrals, may require use of a keyboard--an activity that is foreign and distasteful to many practitioners. It is axiomatic, but necessary, to state that if the physicians will not use the system, it should not be purchased. Third, most sophisticated businesses have an administrator who understands the structure of information flows and the functions of the data system. The system described here requires the attention of such a person, who will manage the information and troubleshoot problems. If a group is small, the administrator may be able to accomplish this task; if it is large, the function may need to be assigned to a full-time manager with backup support staff. Three future developments may mitigate these problems. First, with increasing competition among hardware and software vendors, the price of these systems may decrease to a more affordable level. For the setup described, however, such pricing may be several years away.(ABSTRACT TRUNCATED AT 250 WORDS)


Characterization of dry biopotential electrodes.
Driven by the increased interest in wearable long-term healthcare monitoring systems, varieties of dry electrodes are proposed based on different materials with different patterns and structures. Most of the studies reported in the literature focus on proposing new electrodes and comparing its performance with commercial electrodes. Few papers are about detailed comparison among different dry electrodes. In this paper, printed metal-plate electrodes, textile based electrodes, and spiked electrodes are for the first time evaluated and compared under the same experimental setup. The contact impedance and noise characterization are measured. The in-vivo electrocardiogram (ECG) measurement is applied to evaluate the overall performance of different electrodes. Textile electrodes and printed electrodes gain comparable high-quality ECG signals. The ECG signal obtained by spiked electrodes is noisier. However, a clear ECG envelope can be observed and the signal quality can be easily improved by backend signal processing. The features of each type of electrodes are analyzed and the suitable application scenario is addressed.


Risk factors with intravenous sedation for patients with disabilities.
The purpose of this study was to identify the risk factors associated with low peripheral oxygen saturation (SpO2) and delayed recovery of dental patients with disabilities after intravenous sedation. A total of 1213 patients with disabilities were retrospectively investigated with respect to demographic parameters and sedation conditions. Multivariate logistic analyses were conducted for patients with an SpO2 <90% and a recovery period of >60 minutes to identify the risk factors for poor sedation conditions. A significant odds ratio related to decreased SpO2 was observed for age, sex, midazolam and propofol levels, concurrent use of nitrous oxide, cerebral palsy, Down syndrome, and mental retardation. The most problematic patients were those diagnosed with Down syndrome (odds ratio, 3.003-7.978; 95% confidence interval; P < .001). Decision tree analysis showed an increased risk of decreased SpO2 in males with Down syndrome or after administration of >0.493 mg/kg propofol in combination with midazolam. An increased risk of delayed awakening was seen in patients aged less than 21 years and in males administered >0.032 mg/kg of midazolam. Intravenous sedation for dental patients with disabilities, particularly those with cerebral palsy, Down syndrome, or mental retardation, increases the risk of decreased SpO2. In addition, delayed recovery is expected after midazolam administration.


Pericoronary adipose tissue attenuation predicts outcome of percutaneous intervention for chronic total occlusion.
To investigate the association between pericoronary adipose tissue (PCAT) attenuation (PCATA) and outcomes of chronic total occlusion (CTO) after percutaneous coronary intervention (PCI), and to establish a clinical model that can be easily generalised to predict the outcomes of PCI-CTO. Between September 2015 and September 2019, patients from two centres were enrolled retrospectively. The primary endpoint was a procedural success (defined as achieving residual stenosis of <30% and a grade 3 thrombolysis in myocardial infarction [TIMI] flow). The new predictive model was generated by factors that were determined by multivariate analysis. The PCATA of CTO (PCATA-CTO) score was developed by assigning 1 point for each independent predictor, and then summing all points accrued. In addition, the predictive efficacy and interobserver and intraobserver agreement of PCATA-CTO and other scoring systems based on coronary computed tomography angiography (CCTA) were compared. A total of 201 patients (mean age 58.9 ± 10.8 years, 85% male) were enrolled. The PCI success was achieved in 76% of the lesions. PCAT was higher in the PCI success group (-72.44 ± 10.45HU versus -76.76 ± 10.54 HU, p<0.05). Multivariable analysis yielded severe calcification, lesion length ≥15 mm, and perivascular fat attenuation index (FAI) ≤-69.5HU as independent negative predictors for procedural success. The area under the receiver operating characteristic curves for the PCATA-CTO score was 0.72. Comparing the PCATA-CTO score with other predictive scores, the PCATA-CTO score showed the highest interobserver (kappa = 0.74) and intraobserver agreement (kappa = 0.90, all p<0.01). FAI ≤-69.5HU is an independent negative predictor of procedural success. The PCATA-CTO score improved the reliability of the prediction model. Its potential for clinical implementation requires evaluation.


Rapid evaluation of human biomonitoring data using pattern recognition systems.
Assessing human biomonitoring data often necessitates dealing with fragmentary prior knowledge and a complex set of variables. A procedure for explorative data analysis via decision-tree analysis was undertaken to obtain high-level descriptive summary information on human exposure on a timely basis. This study is based on a subset of monitoring data of the Environmental Specimen Bank for Human Tissues within the German Environmental Specimen Bank (n sigma: 2401: 42/58% males/females; 34/66% born in East/West Germany). Three well-known xenobiotic organochlorines (XOCs) [sum of polychlorinated biphenyls (PCBs) 138 + 153 + 180, pentachlorophenol (PCP), and hexachlorobenzene (HCB)] were used as target variables. Meta-data regarding the samples and individuals were collected via a self-reported questionnaire and used as potential predictor variables. Prior to decision-tree analysis, XOC levels were adjusted (trend, lipids, creatinine, total protein) via stepwise linear regression. Adjusted XOC levels were subsequently utilized to identify relevant predictors of human XOC exposure using Exhaustive CHAID as a common decision-tree algorithm. Although overall tree model quality is generally poor, consistent and plausible predictors for human exposure were identified. Besides time trend and clinical parameters, the predominant predictors for HCB and PCB exposure were birthplace, gender, age, body mass index (BMI), and consumption of milk/dairy products or animal fats. For PCP, predominant predictors were sampling site, gender, and consumption of animal fats. Summing results of decision-tree models and regression models, explained variances for metric scaled XOC are: PCB (34.2%) > HCB (30.3%) > PCP (17.2%). Explorative analysis of human biomonitoring data based on simple decision-tree analysis provides valuable information for planning further investigations and statistical data for analyses to support prediction, consequences, and regulation of XOC.


Oxidation of Fe(II) leads to increased C-2 methylation of pentacyclic triterpenoids in the anoxygenic phototrophic bacterium Rhodopseudomonas palustris strain TIE-1.
Hopanoids are among the most widespread biomarkers of bacteria that are used as indicators for past and present bacterial activity. Our understanding of the production, function, and distribution of hopanoids in bacteria has improved greatly, partly due to genetic, culture-independent studies. Culture-based studies are important to determine hopanoid function and the environmental conditions under which these compounds are produced. This study compares the lipid inventory of Rhodopseudomonas palustris strain TIE-1 under anoxic photoautotrophic conditions using either H2 or Fe(II) as electron donor. The high amount to which adenosylhopane is produced irrespective of the used electron donor suggests a specific function of this compound rather than its exclusive role as an intermediate in bacteriohopanepolyol biosynthesis. C-2 methylated hopanoids and tetrahymanol account for as much as 59% of the respective C-2 methylated/non-methylated homologs during growth with Fe(II) as electron donor, as compared with 24% C-2 methylation for growth with H2 . This observation reveals that C-2 methylated hopanoids have a specific function and are preferentially synthesized in response to elevated Fe(II) concentrations. The presence of C-2 methylated pentacyclic triterpenoids has commonly been used as a biosignature for the interpretation of paleoenvironments. These new findings suggest that increased C-2 methylation may indicate anoxic ferrous conditions, in addition to other environmental stressors that have been previously reported.


Antibacterial activity of plasma from crocodile (Crocodylus siamensis) against pathogenic bacteria.
The Siamese crocodile (Crocodylus siamensis) is a critically endangered species of freshwater crocodiles. Crocodilians live with opportunistic bacterial infection but normally suffer no adverse effects. They are not totally immune to microbial infection, but their resistance thereto is remarkably effective. In this study, crude and purified plasma extracted from the Siamese crocodile were examined for antibacterial activity against clinically isolated, human pathogenic bacterial strains and the related reference strains. Crude plasma was prepared from whole blood of the Siamese crocodile by differential sedimentation. The crude plasma was examined for antibacterial activity by the liquid growth inhibition assay. The scanning electron microscopy was performed to confirm the effect of crude crocodile plasma on the cells of Salmonella typhi ATCC 11778. Effect of crude crocodile plasma on cell viability was tested by MTT assay. In addition, the plasma was purified by anion exchange column chromatography with DEAE-Toyopearl 650 M and the purified plasma was tested for antibacterial activity. Crude plasma was prepared from whole blood of the Siamese crocodile and exhibited substantial antibacterial activities of more than 40% growth inhibition against the six reference strains of Staphylococcus aureus, Salmonella typhi, Escherichia coli, Vibrio cholerae, Pseudomonas aeruginosa, and Staphylococcus epidermidis, and the four clinical isolates of Staphylococcus epidermidis, Pseudomonas aeruginosa, Salmonella typhi, and Vibrio cholerae. Especially, more than 80% growth inhibition was found in the reference strains of Salmonella typhi, Vibrio cholerae, and Staphylococcus epidermidis and in the clinical isolates of Salmonella typhi and Vibrio cholerae. The effect of the crude plasma on bacterial cells of Salmonella typhi, a certain antibacterial material probably penetrates progressively into the cytoplasmic space, perturbing and damaging bacterial membranes. The effect of the crude plasma was not toxic by the yellow tetrazolium bromide (MTT) assay using a macrophage-like cell, RAW 264.7. The pooled four fractions, designated as fractions D1-D4, were obtained by column chromatography, and only fraction D1 showed growth inhibition in the reference strains and the clinical, human pathogenic isolates. The crude and purified plasma from the Siamese crocodile significantly showed antibacterial activity against pathogenic bacteria and reference strains by damage cell membrane of target bacterial cells. From the MTT assay, the Siamese crocodile plasma was not cytotoxic to the cells.


Effects of 5-hydroxytryptamine on the neuronal firing rate of bulbar reticular neurons.
The effects of 5-hydroxytryptamine (5-HT) on neuronal firing rate were studied in the reticular gigantocellular nucleus (GRN) and, for a comparison, in the interstitial (IRN), the parvicellular (PRN) and the lateral (LRN) nuclei, sharing some of GRN functional characteristics. Unitary extracellular recordings performed in anesthetized rats demonstrated that microiontophoretic application of 5-HT modulated the background firing rate in 92% of GRN, in 100% of IRN and LRN, and in 77% of PRN tested neurons. In GRN, 5-HT application induced excitatory responses in 49% of the neurons tested and inhibitions in 43% of them. Both types of effects were dose dependent and appeared scattered throughout the nucleus. Enhancements and decreases of firing rate in response to 5-HT application were also recorded in IRN (58% and 42% respectively), LRN (43% and 57%) and PRN (36% and 41%). The 5-HT(1A) receptor agonist 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT) mimicked 5-HT evoked inhibitions in all the nuclei tested and induced weak inhibitory responses also in neurons excited by 5-HT. The 5-HT2A receptor agonist alphamethyl-5-hydroxytryptamine (alpha-me-5-HT) mimicked excitatory as well as inhibitory responses to 5-HT, the former prevailing in GRN and the latter in the remaining reticular nuclei. Both excitatory and inhibitory responses to 5-HT were partially or totally blocked by the application of 5-HT2 receptor antagonist ketanserin. It is concluded that an extended, strong and differentiated control is exerted by 5-HT on the electrical activity of bulbar reticular neurons. Both 5-HT(1A) and 5-HT(2A) receptors mediate these effects, but the involvement of other receptors appears probable.


Effectiveness and Content Analysis of Interventions to Enhance Oral Antidiabetic Drug Adherence in Adults with Type 2 Diabetes: Systematic Review and Meta-Analysis.
To estimate the pooled effect size of oral antidiabetic drug (OAD) adherence-enhancing interventions and to explore which of the behavior change techniques (BCTs) applied in the intervention groups modified this pooled intervention effect size. We searched relevant studies published until September 3, 2013, on MEDLINE, Embase, PsycInfo, the Cochrane Library, CINAHL, Current Contents Connect, and Web of Science. Selected studies were qualitatively synthesized, and those of at least medium quality were included in the meta-analysis. A random-effects model was used to pool effectiveness (Hedges's g) and to examine heterogeneity (Higgins I(2)). We also explored the influence on the pooled effectiveness of unique intervention BCTs (those delivered to the intervention groups but not control groups in a trial) by estimating their modifying effects. Fourteen studies were selected for the qualitative synthesis and 10 were included in the meta-analysis. The pooled effectiveness of the interventions was 0.21 (95% confidence interval -0.05 to 0.47; I(2) = 82%). Eight unique BCTs were analyzed. "Cope with side effects" (P = 0.003) and "general intention formation" (P = 0.006) had a modifying effect on the pooled effectiveness. The pooled effectiveness of the interventions in which "cope with side effects" was applied was moderate (0.64; 95% confidence interval 0.31-0.96; I(2) = 56%). The overall effectiveness of OAD adherence-enhancing interventions that have been tested is small. Helping patients cope with side effects or formulate desired treatment outcomes could have an impact on the effectiveness of OAD adherence-enhancing interventions. Only those interventions that include helping patients to cope with side effects appear to be particularly effective in improving OAD adherence.


Illicium verum L. (Star Anise) Essential Oil: GC/MS Profile, Molecular Docking Study, In Silico ADME Profiling, Quorum Sensing, and Biofilm-Inhibiting Effect on Foodborne Bacteria.
Illicium verum, or star anise, has many uses ranging from culinary to religious. It has been used in the food industry since ancient times. The main purpose of this study was to determine the chemical composition, antibacterial, antibiofilm, and anti-quorum sensing activities of the essential oil (EO) obtained via hydro-distillation of the aerial parts of Illicium verum. Twenty-four components were identified representing 92.55% of the analyzed essential oil. (E)-anethole (83.68%), limonene (3.19%), and α-pinene (0.71%) were the main constituents of I. verum EO. The results show that the obtained EO was effective against eight bacterial strains to different degrees. Concerning the antibiofilm activity, trans-anethole was more effective against biofilm formation than the essential oil when tested using sub-inhibitory concentrations. The results of anti-swarming activity tested against P. aeruginosa PAO1 revealed that I. verum EO possesses more potent inhibitory effects on the swarming behavior of PAO1 when compared to trans-anethole, with the percentage reaching 38% at a concentration of 100 µg/mL. The ADME profiling of the identified phytocompounds confirmed their important pharmacokinetic and drug-likeness properties. The in silico study using a molecular docking approach revealed a high binding score between the identified compounds with known target enzymes involved in antibacterial and anti-quorum sensing (QS) activities. Overall, the obtained results suggest I. verum EO to be a potentially good antimicrobial agent to prevent food contamination with foodborne pathogenic bacteria.


Mechanisms of lithogenic bile formation in American Indian women with cholesterol gallstones.
Hepatic secretions of biliary lipids were estimated in 43 patients with and without cholesterol gallstones. Studies were carried out by a marker dilution technique employing duodenal intubation with a three-lumen tube. Hourly secretion rates of cholesterol, bile acids, and phospholipids were determined during constant infusion with liquid formula. In 17 American Indian women with gallstones, hourly outputs of biliary bile acids were significantly less than those in 7 Indian men and 12 Caucasian women without gallstones. These findings suggest that a decreased hepatic secretion of bile acids contributes significantly to the production of a lithogenic bile in Indian women. However, in Indian women with gallstones, secretion of biliary cholesterol was also significantly increased, as compared with Caucasian women without stones. Therefore, lithogenic bile in Indian women was, in most cases, due to a combined decrease in bile acid output and increase in cholesterol secretion. In an attempt to determine the mechanisms for these abnormalities, cholesterol balance studies were done in Indian women with gallstones and normal Indian men. Balance data were compared with results reported previously in non-Indian patients studied by the same techniques, and in general, Indian women showed a slight increase in fecal excretion of bile acids. Since bile acids in the enterohepatic circulation were relatively depleted in Indian women, these patients had a reduced fractional reabsorption. However, previous studies have shown that Caucasians can rapidly replenish bile acid pools in the presence of much greater intestinal losses, and it is suggested that among Indian women with gallstones, reduced secretion rates of bile acids are primarily the result of defective homeostatic regulation of bile acid synthesis. In Indian women with gallstones, at least two factors may have contributed to an increased availability of cholesterol in the liver for secretion into bile. First, cholesterol was inadequately converted into bile acids, and secondly, an increased amount of cholesterol was synthesized, as shown by the balance technique. This enhanced production of cholesterol can partially be explained by obesity, but other factors may also play a role.


Rootstock-Scion Interaction Affects the Composition and Pathogen Inhibitory Activity of Tobacco (Nicotiana tabacum L.) Root Exudates.
The composition and allelopathy to Phytophthora nicotianae (the causal agent of tobacco black shank disease) of root exudates from a resistant tobacco (Nicotiana tabacum L.) cultivar Gexin 3, a susceptible cultivar Xiaohuangjin 1025 and their reciprocal grafts were investigated. Grafting with disease-resistant rootstock could improve resistance to black shank; this is closely related to the allelopathy of root exudates. The root exudates from the resistant cultivar inhibited the growth of P. nicotianae, while those from the susceptible cultivar promoted the growth; the grafting varieties had intermediate properties. The root exudate composition differed among cultivars. Gexin 3 was rich in esters and fatty acids, while Xiaohuangjin 1025 contained more hydrocarbons and phenolic acids. The composition of root exudates of grafted cultivars as well as their allelopathy to P. nicotianae were altered, and tended to be close to the composition of cultivar used as rootstock. Eugenol, 4-tert-butylphenol, mono (2-ethylhexyl) phthalate, 4-hydroxybenzoic acid, 2,6-di-tert-butylphenol, dipropyl phthalate, and methyl myristate were identified as the main compounds contributing to inhibitory properties of root exudates. Sorbitol was suggested to play a role in disease induction. Overall, rootstock-scion interaction affected the composition of tobacco root exudates, which may be attributed to the different disease resistance among grafted plants, rootstock and scion.


Probing microstructural information of anisotropic scattering media using rotation-independent polarization parameters.
Polarization parameters contain rich information on the micro- and macro-structure of scattering media. However, many of these parameters are sensitive to the spatial orientation of anisotropic media, and may not effectively reveal the microstructural information. In this paper, we take polarization images of different textile samples at different azimuth angles. The results demonstrate that the rotation insensitive polarization parameters from rotating linear polarization imaging and Mueller matrix transformation methods can be used to distinguish the characteristic features of different textile samples. Further examinations using both experiments and Monte Carlo simulations reveal that the residue rotation dependence in these polarization parameters is due to the oblique incidence illumination. This study shows that such rotation independent parameters are potentially capable of quantitatively classifying anisotropic samples, such as textiles or biological tissues.


Review of 31 vesicointestinal fistulas: diagnosis and management.
Review of 31 cases of enterovesical fistulas treated at the Departments of Urology and General Surgery during the period 1970-1982. In 20 cases (64.5%) the underlying cause was a carcinoma (overall colorectal neoplasm) and in 7 cases (23%) it was an inflammatory disease. Gouverneur's syndrome (suprapubic pain, frequency, dysuria, urinary pain and tenesmus) was present in 17 patients (54.8%). Pneumaturia and fecaluria were present in 18 and rectal micturition in only 5. The diagnosis was based on cystograms in 66.6% of the patients. Other explorations oriented us towards the location of the fistula but only confirmed it in a low percentage (10-30%). The treatment undertaken varied in each case depending on the etiology and the patient's condition: medical (3%), derivative and palliative surgery (23%) and radical surgery (68%).


Diagnosing diabetes mellitus in patients with porphyria cutanea tarda.
The prevalence of diabetes mellitus is increased in patients with porphyria cutanea tarda. Different tests are available for diagnosing and screening for type II diabetes mellitus, however choosing the most suitable test is challenging. The pitfalls in the different tests along with the interfering comorbidities and treatments concerning patients with porphyria cutanea tarda complicate diagnosing these patients with diabetes mellitus. HbA1c, fasting glucose, or oral glucose tolerance are the current available tests, with HbA1c as first choice. Measuring HbA1c requires no fasting, however HbA1c can be false low if the patient is treated with phlebotomy or has liver cirrhosis or chronic hepatitis. Instead fasting glucose and oral glucose tolerance tests can be used if the patient is not acutely ill. If either of the tests give a result in the diagnostic range, the test should be repeated if the patient has no clinical symptoms of diabetes. Diagnosing diabetes mellitus is important for the purpose of early intervention, and this review provides the knowledge needed to diagnose this special patient group properly.


How nurses use National Early Warning Score and Individual Early Warning Score to support their patient risk assessment practice: A fieldwork study.
To explore and describe how the National Early Warning Score (NEWS) and Individual Early Warning Score (I-EWS) are used and how they support nurses' patient risk assessment practice. A qualitative observational fieldwork study drawing on ethnographical principles was performed in six hospitals in two regions of Denmark in 2019. Data were generated from participant observations and informal interviews with 32 nurses across 15 different wards in the hospitals. A total of 180 h of participant observation was performed. The observations lasted between 1.5 and 8 h and were conducted during day or evening shifts. NEWS and I-EWS supported nurses' observations of patients, providing useful knowledge for planning patient care, and prompting critical thinking. However, the risk assessment task was sometimes delegated to less experienced staff members, such as nursing students and healthcare assistants. The Early Warning Score (EWS) systems were often adapted by nurses according to contextual aspects, such as the culture of the speciality in which the nurses worked and their levels of competency. In some situations, I-EWS had the effect of enhancing nurse autonomy and responsibility for decision-making in relation to patient care. EWS systems support nurses' patient risk assessment practice, providing useful information. I-EWS makes it easier to factor the heterogeneity of patients and the clinical situation into the risk assessments. The delegation of risk assessment to other, less experienced staff members pose a risk to patient safety, which needs to be addressed in the ongoing debate regarding the shortage of nurses. The findings of this study can help ward nurses, hospital managers and policymakers to develop and improve strategies for improved person-centred nursing care.


How DNA polymerase X preferentially accommodates incoming dATP opposite 8-oxoguanine on the template.
The modified base 8-oxo-7,8-dihydro-2'-deoxyguanosine (oxoG) is a common DNA adduct produced by the oxidation of DNA by reactive oxygen species. Kinetic data reveal that DNA polymerase X (pol X) from the African swine fever virus incorporates adenine (dATP) opposite to oxoG with higher efficiency than the non-damaged G:C basepair. To help interpret the kinetic data, we perform molecular dynamics simulations of pol X/DNA complexes, in which the template base opposite to the incoming dNTP (dCTP, dATP, dGTP) is oxoG. Our results suggest that pol X accommodates the oxoGsyn:A mispair by sampling closed active conformations that mirror those observed in traditional Watson-Crick complexes. Moreover, for both the oxoGsyn:A and oxoG:C ternary complexes, conformational sampling of the polymerase follows previously described large subdomain movements, local residue motions, and active site reorganization. Interestingly, the oxoGsyn:A system exhibits superior active site geometry in comparison to the oxoG:C system. Simulations for the other mismatch basepair complexes reveal large protein subdomain movement for all systems, except for oxoG:G, which samples conformations close to the open state. In addition, active site geometry and basepairing of the template base with the incoming nucleotide, reveal distortions and misalignments that range from moderate (i.e., oxoG:Asyn) to extreme (i.e., oxoGanti/syn:G). These results agree with the available kinetic data for pol X and provide structural insights regarding the mechanism by which this polymerase can accommodate incoming nucleotides opposite oxoG. Our simulations also support the notion that α-helix E is involved both in DNA binding and active site stabilization. Our proposed mechanism by which pol X can preferentially accommodate dATP opposite template oxoG further underscores the role that enzyme dynamics and conformational sampling operate in polymerase fidelity and function.


On the significance of the vector potential squared.
We consider the gauge potential A and argue that the minimum value of the volume integral of A2 (in Euclidean space) may have physical meaning, particularly in connection with the existence of topological structures. A lattice simulation comparing compact and noncompact "photodynamics" shows a jump in this quantity at the phase transition, supporting this idea.


Antimicrobial resistance among lower respiratory tract isolates of Streptococcus pneumoniae: results of a 1992-93 western Europe and USA collaborative surveillance study. The Alexander Project Collaborative Group.
One thousand, eight hundred and fifty-six Streptococcus pneumoniae strains, collected in 1992 and 1993 from 15 centres in Western Europe and USA were tested for susceptibility to 16 antibiotics. The overall resistance to penicillin was 23% (range 6-54%), with the highest prevalences in Madrid, Barcelona, Toulouse and Cleveland. Seven centres reported low-level penicillin resistance only. Amoxycillin was more active than ceftriaxone against strains with intermediate resistance to penicillin, and at least four-fold more active than cefuroxime; cefaclor and cefixime had poor activity. Against penicillin-resistant strains, ceftriaxone was slightly more active than amoxycillin, cefuroxime exhibited borderline activity and cefixime and cefaclor were inactive. Ten strains fully susceptible to penicillin had MICs of ceftriaxone > or = 0.1 mg/L; this may represent a first step towards the development of cephalosporin resistance. With the exception of fluoroquinolones, resistance to non-beta-lactam antibiotics (chloramphenicol, doxycycline, co-trimoxazole, erythromycin, clarithromycin and azithromycin) was considerably higher in penicillin-resistant strains compared with penicillin-susceptible isolates. Erythromycin-resistant isolates were also resistant to the other macrolides tested.


Determinants of HIV counseling and testing uptake among individuals in long-term sexual relationships in Uganda.
Studies show that HIV counseling and testing (HCT) can improve linkage to HIV prevention, care and treatment services. However, uptake of HCT among couples remains low in most settings. We investigated the determinants of HCT uptake among individuals in long-term relationships in two districts in Uganda. This case-control study was conducted among 787 (400 in Kampala and 387 in Soroti) individuals in long-term sexual relationships, aged 18-54 years, using interviewer-administered questionnaires. Cases were individuals who had ever tested for HIV (selected from health facility records and traced in the community for interview) while controls were individuals who had never tested for HIV, identified from the same community as the cases. Data were collected on sociodemographic and behavioral characteristics; entered into FoxPro and analyzed using STATA version 12.1. We performed multivariable logistic regression to estimate the odds ratio (OR) and 95% Confidence Intervals (95%CI) associated with prior HCT and couples' HCT uptake, controlling for suspected confounders. Of the 787 participants, 522 had ever tested for HIV (cases) while 265 had never tested for HIV (controls). Compared to those that had never tested for HIV, those that had ever tested for HIV were significantly more likely to be females (Adj. OR=3.23, 95%CI: 2.27, 4.60), to be 25-29 years old (Adj. OR=2.15, 95%CI: 1.32, 3.50), to report exposure to a couples' HCT promotional campaign (Adj. OR=2.01, 95%CI: 1.30, 3.10) and to believe that HIV discordance is possible among married couples (Adj. OR=1.77, 95%CI: 1.20, 2.63). Compared to individuals that had ever received individual HCT, those that had ever received couples' HCT were significantly more likely to report prior discussion of HIV testing with partner (Adj. OR=4.35, 95%CI: 2.61, 7.28) and to be residents of Soroti district (Adj. OR=6.01, 95%CI: 3.74, 9.65). Prior HCT was significantly associated with female gender and exposure to a couples' HCT promotional campaign while prior couples' HCT was significantly associated with prior discussion of HIV testing with partner. To increase HIV testing among couples, these findings suggest a need for HCT promotional campaigns that promote communication about HCT between partners.


[Bisphosphonate-related osteonecrosis of the jaw].
Osteonecrosis of the jaw in association with long-term use of bisphosphonates (BRONJ) is a relatively rare but serious side effect that is difficult to treat. The incidence of BRONJ in patients treated for osteoporosis is low at 0.1%. The incidence in cancer patients treated with high doses of intravenous bisphosphonates is higher, ranging between 3% and 10%. Risk factors for BRONJ are invasive treatments such as tooth extractions, root canal procedures and the placement of dental implants, as well as trauma caused by pressure from poorly fitting dental prostheses. High-risk patients should be examined by a dentist or an oral surgeon and, if necessary, undergo dental treatment prior to treatment with bisphosphonates. All patients taking bisphosphonates should maintain good oral hygiene, receive regular dental examinations and see a dentist if any oral symptoms develop. Physicians who prescribe medication as well as the patient's dentist and oral surgeon should be aware of the use of bisphosphonates and BRONJ as a possible adverse reaction. This requires cooperation and the exchange of information between a patient's health care providers.


Dimension, anatomy and morphology of the mesiobuccal root canal system in maxillary molars.
To increase our understanding of the root canal system, we examined the mesiobuccal (MB) roots of maxillary first and second molars, which are considered to be one of the most complex root canal systems. Uninstrumented MB roots from 153 teeth were imbedded, sectioned, and observed at 8x using a stereomicroscope for main canal numbers, isthmus presence, and dimensional size of canals and dentin walls. The number of canals observed in maxillary first and second molars was 20% and 38.1% for one canal, 79.8% and 60.3% for two canals, and 1.1% and 1.6% for three canals, respectively. The buccal canal was larger than lingual or middle canals at all levels of the root. The average distance between the two main canals was 1.2 +/- 0.6 mm in first molars and 1.78 +/- 0.6 mm in second molars. Isthmus tissue increased greatly at 3.6 mm from the apex, suggesting optimal root resection at this level. Little differences in thickness between mesial and distal canal walls were seen until reaching the coronal sections of the root where the average canal wall thickness was found to be thinner (33%) on the distal, suggesting a "danger zone" for maxillary molars at a level where the root joins the crown of the tooth. The observations made here provide a more precise understanding of the maxillary MB root system. Orthograde and retrograde root canal therapy might be improved with a comprehensive understanding of pulpal morphology throughout the entire MB root.


Long-term sensitization in Aplysia: biophysical correlates in tail sensory neurons.
A fundamental problem in the cellular analysis of learning and memory is the identification of the neuronal substrates of long-term information storage and their relation to short-term cellular alterations. In this report, biophysical correlates of long-term sensitization of a simple withdrawal reflex in the mollusc Aplysia were examined. A voltage-clamp analysis of the sensory neurons that control the reflex, 24 hours after sensitization training, revealed a significant reduction in net outward current. The results indicate that one mechanism for the storage of long-term sensitization is the regulation of membrane currents that influence the characteristics of the action potential and the excitability of individual neurons. The results also provide insights into the relation between short- and long-term sensitization in that the biophysical loci involved in the storage of long-term sensitization appear similar to those involved in short-term sensitization.