Advertising strategies to increase public knowledge of the warning signs of stroke.
Public awareness of the warning signs of stroke is important. As part of an educational campaign using mass media, the Heart and Stroke Foundation of Ontario conducted public opinion polling in 4 communities to track the level of awareness of the warning signs of stroke and to determine the impact of different media strategies. Telephone surveys were conducted among members of the general public in 1 control and 3 test communities before and after mass media campaigns. The main outcome measure used to determine effectiveness of the campaigns was the ability to name > or =2 warning signs of stroke. In communities exposed to television advertising, ability to name the warning signs of stroke increased significantly. There was no significant change in the community receiving print (newspaper) advertising, and the control community experienced a decrease. Television increased the knowledge of both men and women and of people with less than a secondary school education but not of those > or =65 years of age. Intermittent, low-level television advertising was as effective as continuous, high-level television advertising. Results of this survey can be used to guide mass media-buying strategies for public health education.


Phase-shifting for nonseparable 2-D Haar wavelets.
In this paper, we present a novel and efficient solution to phase-shifting 2-D nonseparable Haar wavelet coefficients. While other methods either modify existing wavelets or introduce new ones to handle the lack of shift-invariance, we derive the explicit relationships between the coefficients of the shifted signal and those of the unshifted one. We then establish their computational complexity, and compare and demonstrate the superior performance of the proposed approach against classical interpolation tools in terms of accumulation of errors under successive shifting.


Granzyme B degradation by autophagy decreases tumor cell susceptibility to natural killer-mediated lysis under hypoxia.
Recent studies demonstrated that autophagy is an important regulator of innate immune response. However, the mechanism by which autophagy regulates natural killer (NK) cell-mediated antitumor immune responses remains elusive. Here, we demonstrate that hypoxia impairs breast cancer cell susceptibility to NK-mediated lysis in vitro via the activation of autophagy. This impairment was not related to a defect in target cell recognition by NK cells but to the degradation of NK-derived granzyme B in autophagosomes of hypoxic cells. Inhibition of autophagy by targeting beclin1 (BECN1) restored granzyme B levels in hypoxic cells in vitro and induced tumor regression in vivo by facilitating NK-mediated tumor cell killing. Together, our data highlight autophagy as a mechanism underlying the resistance of hypoxic tumor cells to NK-mediated lysis. The work presented here provides a cutting-edge advance in our understanding of the mechanism by which hypoxia-induced autophagy impairs NK-mediated lysis in vitro and paves the way for the formulation of more effective NK cell-based antitumor therapies.


Biological functionality of soyasaponins and soyasapogenols.
Soyasaponins are a group of structurally complex oleanane triterpenoids primarily found in soybeans and have diverse biological properties. The recent investigations and findings (since 2000) regarding the biological functions of soyasaponins and their aglycones, including their anti-inflammatory, antimutagenic, anticarcinogenic, antimicrobial, and hepato- and cardiovascular-protective activities, are herein summarized. The primary conclusion is that the use of soyasaponins and soyasapogenols in functional foods should be considered.


On the abundance of polyploids in flowering plants.
The wide distribution of polyploidy among plants has led to a variety of theories for the evolutionary advantages of polyploidy. Here we claim that the abundance of polyploidy may be the result of a simple ratcheting process that does not require evolutionary advantages due to the biological properties of organisms. The evolution of polyploidy is a one-way process in which chromosome number can increase but not decrease. Using a simple mathematical model, we show that average ploidal level within a plant lineage can continually increase to the levels observed today, even if there are ecological or physiological disadvantages to higher ploidy. The model allowed us to estimate the average net speciation and polyploidy rates for ten angiosperm genera. Based on these estimates, the model predicts distributions of ploidal levels statistically similar to those observed in nine of the 10 genera.


Independent predictors of delay in emergence from general anesthesia.
Some patients with intellectual disabilities spend longer than others in emergence from ambulatory general anesthesia for dental treatment. Although antiepileptic drugs and anesthetics might be involved, an independent predictor for delay of the emergence remains unclear. Thus, a purpose of this study is to identify independent factors affecting the delay of emergence from general anesthesia. This was a retrospective cohort study in dental patients with intellectual disabilities. Patients in need of sedative premedication were removed from participants. The outcome was time until emergence from general anesthesia. Stepwise multivariate regression analysis was used to extract independent factors affecting the outcome. Antiepileptic drugs and anesthetic parameters were included as predictor variables. The study included 102 cases. Clobazam, clonazepam, and phenobarbital were shown to be independent determinants of emergence time. Parameters relating to anesthetics, patients' backgrounds, and dental treatment were not independent factors. Delay in emergence time in ambulatory general anesthesia is likely to be related to the antiepileptic drugs of benzodiazepine or barbiturates in patients with intellectual disability.


Antimicrobial Polymers: The Potential Replacement of Existing Antibiotics?
Antimicrobial resistance is now considered a major global challenge; compromising medical advancements and our ability to treat infectious disease. Increased antimicrobial resistance has resulted in increased morbidity and mortality due to infectious diseases worldwide. The lack of discovery of novel compounds from natural products or new classes of antimicrobials, encouraged us to recycle discontinued antimicrobials that were previously removed from routine use due to their toxicity, e.g., colistin. Since the discovery of new classes of compounds is extremely expensive and has very little success, one strategy to overcome this issue could be the application of synthetic compounds that possess antimicrobial activities. Polymers with innate antimicrobial properties or that have the ability to be conjugated with other antimicrobial compounds create the possibility for replacement of antimicrobials either for the direct application as medicine or implanted on medical devices to control infection. Here, we provide the latest update on research related to antimicrobial polymers in the context of ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.) pathogens. We summarise polymer subgroups: compounds containing natural peptides, halogens, phosphor and sulfo derivatives and phenol and benzoic derivatives, organometalic polymers, metal nanoparticles incorporated into polymeric carriers, dendrimers and polymer-based guanidine. We intend to enhance understanding in the field and promote further work on the development of polymer based antimicrobial compounds.


Assessment of an Updated Neonatal Research Network Extremely Preterm Birth Outcome Model in the Vermont Oxford Network.
The Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) extremely preterm birth outcome model is widely used for prognostication by practitioners caring for families expecting extremely preterm birth. The model provides information on mean outcomes from 1998 to 2003 and does not account for substantial variation in outcomes among US hospitals. To update and validate the NRN extremely preterm birth outcome model for most extremely preterm infants in the United States. This prognostic study included 3 observational cohorts from January 1, 2006, to December 31, 2016, at 19 US centers in the NRN (derivation cohort) and 637 US centers in Vermont Oxford Network (VON) (validation cohorts). Actively treated infants born at 22 weeks' 0 days' to 25 weeks' 6 days' gestation and weighing 401 to 1000 g, including 4176 in the NRN for 2006 to 2012, 45 179 in VON for 2006 to 2012, and 25 969 in VON for 2013 to 2016, were studied. VON cohorts comprised more than 85% of eligible US births. Data analysis was performed from May 1, 2017, to March 31, 2019. Predictive variables used in the original model, including infant sex, birth weight, plurality, gestational age at birth, and exposure to antenatal corticosteroids. The main outcome was death before discharge. Secondary outcomes included neurodevelopmental impairment at 18 to 26 months' corrected age and measures of hospital resource use (days of hospitalization and ventilator use). Among 4176 actively treated infants in the NRN cohort (48% female; mean [SD] gestational age, 24.2 [0.8] weeks), survival was 63% vs 62% among 3702 infants in the era of the original model (47% female; mean [SD] gestational age, 24.2 [0.8] weeks). In the concurrent (2006-2012) VON cohort, survival was 66% among 45 179 actively treated infants (47% female; mean [SD] gestational age, 24.1 [0.8] weeks) and 70% among 25 969 infants from 2013 to 2016 (48% female; mean [SD] gestational age, 24.1 [0.8] weeks). Model C statistics were 0.74 in the 2006-2012 validation cohort and 0.73 in the 2013-2016 validation cohort. With the use of decision curve analysis to compare the model with a gestational age-only approach to prognostication, the updated model showed a predictive advantage. The birth hospital contributed equally as much to prediction of survival as gestational age (20%) but less than the other factors combined (60%). An updated model using well-known factors to predict survival for extremely preterm infants performed moderately well when applied to large US cohorts. Because survival rates change over time, the model requires periodic updating. The hospital of birth contributed substantially to outcome prediction.


Reasoning Graph Networks for Kinship Verification: From Star-Shaped to Hierarchical.
In this paper, we investigate the problem of facial kinship verification by learning hierarchical reasoning graph networks. Conventional methods usually focus on learning discriminative features for each facial image of a paired sample and neglect how to fuse the obtained two facial image features and reason about the relations between them. To address this, we propose a Star-shaped Reasoning Graph Network (S-RGN). Our S-RGN first constructs a star-shaped graph where each surrounding node encodes the information of comparisons in a feature dimension and the central node is employed as the bridge for the interaction of surrounding nodes. Then we perform relational reasoning on this star graph with iterative message passing. The proposed S-RGN uses only one central node to analyze and process information from all surrounding nodes, which limits its reasoning capacity. We further develop a Hierarchical Reasoning Graph Network (H-RGN) to exploit more powerful and flexible capacity. More specifically, our H-RGN introduces a set of latent reasoning nodes and constructs a hierarchical graph with them. Then bottom-up comparative information abstraction and top-down comprehensive signal propagation are iteratively performed on the hierarchical graph to update the node features. Extensive experimental results on four widely used kinship databases show that the proposed methods achieve very competitive results.


Structural determinants for binding to angiotensin converting enzyme 2 (ACE2) and angiotensin receptors 1 and 2.
Angiotensin converting enzyme 2 (ACE2) is a zinc carboxypeptidase involved in the renin-angiotensin system (RAS) and inactivates the potent vasopressive peptide angiotensin II (Ang II) by removing the C-terminal phenylalanine residue to yield Ang1-7. This conversion inactivates the vasoconstrictive action of Ang II and yields a peptide that acts as a vasodilatory molecule at the Mas receptor and potentially other receptors. Given the growing complexity of RAS and level of cross-talk between ligands and their corresponding enzymes and receptors, the design of molecules with selectivity for the major RAS binding partners to control cardiovascular tone is an on-going challenge. In previous studies we used single β-amino acid substitutions to modulate the structure of Ang II and its selectivity for ACE2, AT1R, and angiotensin type 2 (AT2R) receptor. We showed that modification at the C-terminus of Ang II generally resulted in more pronounced changes to secondary structure and ligand binding, and here, we further explore this region for the potential to modulate ligand specificity. In this study, (1) a library of 47 peptides derived from the C-terminal tetrapeptide sequence (-IHPF) of Ang II was synthesized and assessed for ACE2 binding, (2) the terminal group requirements for high affinity ACE2 binding were explored by and N- and C-terminal modification, (3) high affinity ACE2 binding chimeric AngII analogs were then synthesized and assessed, (4) the structure of the full-length Ang II analogs were assessed by circular dichroism, and (5) the Ang II analogs were assessed for AT1R/AT2R selectivity by cell-based assays. Studies on the C-terminus of Ang II demonstrated varied specificity at different residue positions for ACE2 binding and four Ang II chimeric peptides were identified as selective ligands for the AT2 receptor. Overall, these results provide insight into the residue and structural requirements for ACE2 binding and angiotensin receptor selectivity.


The election of Sarah McNutt as the first woman member of the American Neurological Association.
The authors investigated the early women physicians of the New York Infirmary for Women and Children and their role in shaping the career and accomplishments of their student and later colleague, Dr. Sarah J. McNutt. These influences eventually led McNutt to be inducted into the American Neurologic Association (ANA). McNutt was educated at the New York Infirmary for Women and Children by early women physicians including Drs. Elizabeth and Emily Blackwell and Mary Putnam Jacobi. McNutt worked to improve the educational opportunities for practicing physicians and nurses by developing postgraduate lectures and organizations. With her early colleagues she developed the New York Infirmary for Women and Children into a reputable hospital and woman's medical college. One of the consultants to the New York Infirmary for Women and Children was Royal W. Amidon, secretary of the ANA in 1883. McNutt's close association with the Clinical Society of the New York Post Graduate Medical School and Hospital brought her into direct contact with other prominent ANA members including C.L. Dana and W.A. Hammond. In 1884, McNutt was nominated by Amidon and Hammond as the first woman member to the ANA and was elected. Her ANA thesis was Double Infantile Spastic Hemiplegia. McNutt was elected into the ANA at a time when women physicians were first being recognized and included into mainstream medicine. Her historic election acknowledged her accomplishments and highlighted the proactive role of the early ANA in forging new medical policies in the United States.


Selective Enhancement of Object Representations through Multisensory Integration.
Objects are the fundamental building blocks of how we create a representation of the external world. One major distinction among objects is between those that are animate versus those that are inanimate. In addition, many objects are specified by more than a single sense, yet the nature by which multisensory objects are represented by the brain remains poorly understood. Using representational similarity analysis of male and female human EEG signals, we show enhanced encoding of audiovisual objects when compared with their corresponding visual and auditory objects. Surprisingly, we discovered that the often-found processing advantages for animate objects were not evident under multisensory conditions. This was due to a greater neural enhancement of inanimate objects-which are more weakly encoded under unisensory conditions. Further analysis showed that the selective enhancement of inanimate audiovisual objects corresponded with an increase in shared representations across brain areas, suggesting that the enhancement was mediated by multisensory integration. Moreover, a distance-to-bound analysis provided critical links between neural findings and behavior. Improvements in neural decoding at the individual exemplar level for audiovisual inanimate objects predicted reaction time differences between multisensory and unisensory presentations during a Go/No-Go animate categorization task. Links between neural activity and behavioral measures were most evident at intervals of 100-200 ms and 350-500 ms after stimulus presentation, corresponding to time periods associated with sensory evidence accumulation and decision-making, respectively. Collectively, these findings provide key insights into a fundamental process the brain uses to maximize the information it captures across sensory systems to perform object recognition.SIGNIFICANCE STATEMENT Our world is filled with ever-changing sensory information that we are able to seamlessly transform into a coherent and meaningful perceptual experience. We accomplish this feat by combining different stimulus features into objects. However, despite the fact that these features span multiple senses, little is known about how the brain combines the various forms of sensory information into object representations. Here, we used EEG and machine learning to study how the brain processes auditory, visual, and audiovisual objects. Surprisingly, we found that nonliving (i.e., inanimate) objects, which are more difficult to process with one sense alone, benefited the most from engaging multiple senses.


In-situ biofilm characterization in membrane systems using Optical Coherence Tomography: formation, structure, detachment and impact of flux change.
Biofouling causes performance loss in spiral wound nanofiltration (NF) and reverse osmosis (RO) membrane operation for process and drinking water production. The development of biofilm formation, structure and detachment was studied in-situ, non-destructively with Optical Coherence Tomography (OCT) in direct relation with the hydraulic biofilm resistance and membrane performance parameters: transmembrane pressure drop (TMP) and feed-channel pressure drop (FCP). The objective was to evaluate the suitability of OCT for biofouling studies, applying a membrane biofouling test cell operated at constant crossflow velocity (0.1 m s(-1)) and permeate flux (20 L m(-2)h(-1)). In time, the biofilm thickness on the membrane increased continuously causing a decline in membrane performance. Local biofilm detachment was observed at the biofilm-membrane interface. A mature biofilm was subjected to permeate flux variation (20 to 60 to 20 L m(-2)h(-1)). An increase in permeate flux caused a decrease in biofilm thickness and an increase in biofilm resistance, indicating biofilm compaction. Restoring the original permeate flux did not completely restore the original biofilm parameters: After elevated flux operation the biofilm thickness was reduced to 75% and the hydraulic resistance increased to 116% of the original values. Therefore, after a temporarily permeate flux increase the impact of the biofilm on membrane performance was stronger. OCT imaging of the biofilm with increased permeate flux revealed that the biofilm became compacted, lost internal voids, and became more dense. Therefore, membrane performance losses were not only related to biofilm thickness but also to the internal biofilm structure, e.g. caused by changes in pressure. Optical Coherence Tomography proved to be a suitable tool for quantitative in-situ biofilm thickness and morphology studies which can be carried out non-destructively and in real-time in transparent membrane biofouling monitors.


RpoS-regulated genes of Escherichia coli identified by random lacZ fusion mutagenesis.
RpoS is a conserved alternative sigma factor that regulates the expression of many stress response genes in Escherichia coli. The RpoS regulon is large but has not yet been completely characterized. In this study, we report the identification of over 100 RpoS-dependent fusions in a genetic screen based on the differential expression of an operon-lacZ fusion bank in rpoS mutant and wild-type backgrounds. Forty-eight independent gene fusions were identified, including several in well-characterized RpoS-regulated genes, such as osmY, katE, and otsA. Many of the other fusions mapped to genes of unknown function or to genes that were not previously known to be under RpoS control. Based on the homology to other known bacterial genes, some of the RpoS-regulated genes of unknown functions are likely important in nutrient scavenging.


Uses of granulocyte-macrophage colony-stimulating factor in vaccine development.
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a potent cytokine capable of inducing differentiation, proliferation, and activation of a variety of immunologically active cell populations. In addition to its effects on stimulating granulocytic hematopoiesis, it also facilitates development of both humoral and cellular mediated immunity. Accordingly, strategies involving the use of GM-CSF as a vaccine adjuvant have attracted considerable attention. These strategies include the systemic administration of soluble GM-CSF with an immunogen, and also its use as part of gene therapy approaches to immunization. Because of the potency of this cytokine as an immune adjuvant, particular interest has focused on its use to overcome poorly immunogenic antigens such as those associated with intracellular infections and cancer. This review focuses on recent advances in the use of GM-CSF as a vaccine adjuvant.


Mammalian cyclin D1/Cdk4 complexes induce cell growth in Drosophila.
The Drosophila melanogaster cyclin dependent protein kinase complex CycD/Cdk4 has been shown to regulate cellular growth (accumulation of mass) as well as proliferation (cell cycle progression). In contrast, the orthologous mammalian complex has been shown to regulate cell cycle progression, but possible functions in growth control have not been addressed directly. To test whether mammalian Cyclin D1/Cdk4 complexes are capable of driving cell growth, we expressed such a complex in Drosophila. Using assays that distinguish between mass increase and cell cycle progression, we found that this complex stimulated cell growth, like its Drosophila counterpart. Furthermore, Hif-1 prolyl hydroxylase (Hph) is required for both complexes to drive growth. Our data suggest that the growth-specific function of CycD/Cdk4 is conserved from arthropods to mammals.


Inter-Observer Agreement between Low-Dose and Standard-Dose CT with Soft and Sharp Convolution Kernels in COVID-19 Pneumonia.
Computed tomography (CT) has been an essential diagnostic tool during the COVID-19 pandemic. The study aimed to develop an optimal CT protocol in terms of safety and reliability. For this, we assessed the inter-observer agreement between CT and low-dose CT (LDCT) with soft and sharp kernels using a semi-quantitative severity scale in a prospective study (Moscow, Russia). Two consecutive scans with CT and LDCT were performed in a single visit. Reading was performed by ten radiologists with 3-25 years' experience. The study included 230 patients, and statistical analysis showed LDCT with a sharp kernel as the most reliable protocol (percentage agreement 74.35 ± 43.77%), but its advantage was marginal. There was no significant correlation between radiologists' experience and average percentage agreement for all four evaluated protocols. Regarding the radiation exposure, CTDIvol was 3.6 ± 0.64 times lower for LDCT. In conclusion, CT and LDCT with soft and sharp reconstructions are equally reliable for COVID-19 reporting using the "CT 0-4" scale. The LDCT protocol allows for a significant decrease in radiation exposure but may be restricted by body mass index.


A brain-dead pregnant woman with prolonged somatic support and successful neonatal outcome: A grand rounds case with a detailed review of literature and ethical considerations.
There are increased reports in the medical literature of brain death during pregnancy. In these rare cases, the decision was either to consider discontinuing homeostatic support and mechanical ventilation with an understanding that the fetus then will also die, or to continue full support in an attempt to prolong pregnancy for the purpose of maintaining the fetus alive until maturity. We report the first case in the United Arab Emirates and in literature of somatic support that extended up to 110 days with the successful delivery of a viable fetus. A 35-year-old woman suffered intracranial hemorrhage during the 16(th) week of pregnancy that lead to brain death despite maximal surgical and medical management. Upon confirmation of this diagnosis, the patient received full ventilatory and homeostatic support required to prolong gestation and improve the survival prognosis of her fetus. The status of the patient was discussed in a multidisciplinary approach and with the full involvement of her family. Somatic support continued until the patient was 32 of weeks gestation. Obstetric complications of the patient were frequently assessed and managed. Lower segment cesarean section (LSCS) was then performed. A preterm male in breech presentation was delivered with an average weight of 750 gm, and an Apgar score of 6, 7, and 9 at 1, 5, and 10 minutes, respectively. Prolonging somatic support in a pregnant woman with brain death to allow fetal survival resulted in a successful outcome in terms of saving the life of the fetus. The results are consistent with previous published case reports in the literature on the appropriateness and safety of such a strategy that involved an intensive multidisciplinary approach. Despite being a tragedy, maternal death can represent an opportunity to save the life of the fetus and for organ donation. Consensus future recommendations that can guide the management of similar conditions may also be adapted, especially with the growing medical experience in this context.


Platelet rich plasma: Effective treatment for repairing of spinal cord injury in rat.
The aim of the present study was to evaluate the effect of PRP on the repair of spinal cord injury in rat model. Rats were randomly divided into three groups with six rats in each group. Then, spinal cord injury was performed under general anesthesia using "weight dropping" method. Control group included rats receiving normal saline, group two received PRP 1 week after injury; group three received PRP 24 h after injury. The motor function was assessed weekly using the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale. Anterograde tracing was performed for evaluation of axon regeneration. Motor recovery was significantly better in the rats treated with PRP 24 h after injury than the control group. In the rats treated with PRP 1 week after injury and rats treated with PRP 24 h after injury, the average numbers of BDA-labeled axons were statistically different from the control group. Our experimental study demonstrated positive effects of platelet rich plasma on nerve regeneration after spinal cord injury.


Effect of implementing routine early invasive strategy on one-year mortality in patients with acute myocardial infarction.
The aim of the present study was to investigate whether the implementation of an early invasive strategy for unselected patients with acute myocardial infarction (AMI) would be associated with reduced long-term mortality compared to a conservative approach. In this prospective observational cohort study of consecutive patients admitted for AMI in 2003 (conservative cohort, n = 311) and 2006 (invasive cohort [IC], n = 307), an 11% absolute and 41% relative reduction in 1-year mortality was found for patients with AMI in the IC compared to the conservative cohort (p = 0.001). These findings were consistent after adjustment for age, gender, previous AMI, previous stroke, diabetes, smoking status, previous left ventricular systolic dysfunction, and serum creatinine at admission (hazard ratio 0.54, 95% confidence interval 0.38 to 0.78) and Global Registry of Acute Coronary Events risk score (hazard ratio 0.67, 95% confidence interval 0.46 to 0.97). More patients with ST-segment elevation myocardial infarction received primary percutaneous coronary intervention in the IC (57% vs 3%, p <0.001), and a sixfold (25% vs 4%, p <0.001) increase in early percutaneous coronary intervention (<72 hours) for patients with non-ST-segment elevation myocardial infarction was observed. A greater proportion of patients in the IC received clopidogrel, aspirin, and statins during follow-up; otherwise, the secondary prevention measures were similar in the 2 cohorts. In conclusion, the introduction of a strategy for routine transfer to a high-volume percutaneous coronary intervention center for early invasive therapy was accompanied by a substantial reduction in mortality among unselected patients with AMI. Differences in unmeasured confounders might have accounted for a part of the difference in outcome.


Bioprocess strategies for enhancing the outdoor production of Nannochloropsis gaditana: an evaluation of the effects of pH on culture performance in tubular photobioreactors.
A priority of the industrial applications of microalgae is the reduction of production costs while maximizing algae biomass productivity. The purpose of this study was to carry out a comprehensive evaluation of the effects of pH control on the production of Nannochloropsis gaditana in tubular photobioreactors under external conditions while considering the environmental, biological, and operational parameters of the process. Experiments were carried out in 3.0 m3 tubular photobioreactors under outdoor conditions. The pH values evaluated were 6.0, 7.0, 8.0, 9.0, and 10.0, which were controlled by injecting pure CO2 on-demand. The results have shown that the ideal pH for microalgal growth was 8.0, with higher values of biomass productivity (Pb) (0.16 g L-1 d-1), and CO2 use efficiency ([Formula: see text]) (74.6% w w-1); [Formula: see text]/biomass value obtained at this pH (2.42 [Formula: see text] gbiomass-1) was close to the theoretical value, indicating an adequate CO2 supply. At this pH, the system was more stable and required a lower number of CO2 injections than the other treatments. At pH 6.0, there was a decrease in the Pb and [Formula: see text]; cultures at pH 10.0 exhibited a lower Pb and photosynthetic efficiency as well. These results imply that controlling the pH at an optimum value allows higher CO2 conversions in biomass to be achieved and contributes to the reduction in costs of the microalgae production process.


Outcome following surgery for thoracic outlet syndrome.
the diagnosis of thoracic outlet syndrome (TOS) relies heavily on subjective rather than objective assessment criteria. Subsequently, published results after surgical decompression vary considerably. This study aimed to use a symptom-based patient-directed questionnaire to assess the outcome after decompression for TOS. sixty patients who underwent decompression procedures were identified from a prospectively maintained vascular database. Patient records were analysed for details regarding initial presentation, investigation, type of procedure used for decompression and management. Outcome questionnaires were sent to all identified patients to give a patient-based outcome measure. eighty-four per cent of patients responded. In 90% of these patients there was an improvement in symptoms post-surgery with a median follow up of 43 months. The results were not influenced by the procedure or approach used. surgery remains an effective tool in the management of TOS. A simple patient-directed questionnaire as used in this study could assist in the standardisation of outcome assessment.


Surface orientation, modulation frequency and the detection and perception of depth defined by binocular disparity and motion parallax.
Binocular disparity and motion parallax provide information about the spatial structure and layout of the world. Descriptive similarities between the two cues have often been noted which have been taken as evidence of a close relationship between them. Here, we report two experiments which investigate the effect of surface orientation and modulation frequency on (i) a threshold detection task and (ii) a supra-threshold depth-matching task using sinusoidally corrugated surfaces defined by binocular disparity or motion parallax. For low frequency corrugations, an orientation anisotropy was observed in both domains, with sensitivity decreasing as surface orientation was varied from horizontal to vertical. In the depth-matching task, for surfaces defined by binocular disparity the greatest depth was seen for oblique orientations. For surfaces defined by motion parallax, perceived depth was found to increase as surface orientation was varied from horizontal to vertical. In neither case was perceived depth for supra-threshold surfaces related to threshold performance in any simple manner. These results reveal clear differences between the perception of depth from binocular disparity or motion parallax, and between perception at threshold and supra-threshold levels of performance.


Genome-wide RNA-Sequencing analysis identifies a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery.
Fibrosis-related events play a part in most blinding diseases worldwide. However, little is known about the mechanisms driving this complex multifactorial disease. Here we have carried out the first genome-wide RNA-Sequencing study in human conjunctival fibrosis. We isolated 10 primary fibrotic and 7 non-fibrotic conjunctival fibroblast cell lines from patients with and without previous glaucoma surgery, respectively. The patients were matched for ethnicity and age. We identified 246 genes that were differentially expressed by over two-fold and p < 0.05, of which 46 genes were upregulated and 200 genes were downregulated in the fibrotic cell lines compared to the non-fibrotic cell lines. We also carried out detailed gene ontology, KEGG, disease association, pathway commons, WikiPathways and protein network analyses, and identified distinct pathways linked to smooth muscle contraction, inflammatory cytokines, immune mediators, extracellular matrix proteins and oncogene expression. We further validated 11 genes that were highly upregulated or downregulated using real-time quantitative PCR and found a strong correlation between the RNA-Seq and qPCR results. Our study demonstrates that there is a distinct fibrosis gene signature in the conjunctiva after glaucoma surgery and provides new insights into the mechanistic pathways driving the complex fibrotic process in the eye and other tissues.


Combining weed efficacy, economics and environmental considerations for improved herbicide management in the Great Barrier Reef catchment area.
The current Australian sugarcane industry transition toward adoption of an 'alternative' herbicide strategy as part of improved environmental stewardship is increasingly complicated by recent farming system, regulatory and herbicidal product changes. This study quantified and compared the efficacy, economic costs and environmental risk profiles of a range of established, emerging, and recently registered pre-emergent herbicides across field trials in the Wet Tropics region of North Queensland. Several herbicides were effective on certain weed species, but lacked broad spectrum control. Better efficacy results from products with multiple active ingredients (i.e., imazapic-hexazinone) demonstrated the benefits of using mixtures of active ingredients to widen the spectrum of weed control efficacy. All tested pre-emergent herbicides behaved quite similarly in terms of their propensity for off-site movement in water (surface runoff losses generally >10% of active applied), with their losses largely driven by their application rate. Herbicides with lower application rates consistently contributed less to the total herbicide loads measured in surface runoff. Results demonstrated alternative choices from the more environmentally problematic herbicides (such as diuron) are available with effective alternative formulations providing between 4 and 29 times less risk than the traditional diuron-hexazinone 'full rate'. However, considerable challenges still face canegrowers in making cost-effective decisions on sustainable herbicide selection. Additional research and effective grower extension are required to address information gaps in issues such as specific weed control efficacy of alternative herbicides and potential blending of some herbicides for more effective broad spectrum weed control, while also minimising environmental risks.


Early prediction of massive transfusion in trauma: simple as ABC (assessment of blood consumption)?
Massive transfusion (MT) occurs in about 3% of civilian and 8% of military trauma patients. Although many centers have implemented MT protocols, most do not have a standardized initiation policy. The purpose of this study was to validate previously described MT scoring systems and compare these to a simplified nonlaboratory dependent scoring system (Assessment of Blood Consumption [ABC] score). Retrospective cohort of all level I adult trauma patients transported directly from the scene (July 2005 to June 2006). Trauma-Associated Severe Hemorrhage (TASH) and McLaughlin scores calculated according to published methods. ABC score was assigned based on four nonweighted parameters: penetrating mechanism, positive focused assessment sonography for trauma, arrival systolic blood pressure of 90 mm Hg or less, and arrival heart rate > or = 120 bpm. Area under the receiver operating characteristic curve (AUROC) used to compare scoring systems. Five hundred ninety-six patients were available for analysis; and the overall MT rate of 12.4%. Patients receiving MT had higher TASH (median, 6 vs. 13; p < 0.001), McLaughlin (median, 2.4 vs. 3.4; p < 0.001) and ABC (median, 1 vs. 2; p < 0.001) scores. TASH (AUROC = 0.842), McLaughlin (AUROC = 0.846), and ABC (AUROC = 0.842) scores were all good predictors of MT, and the difference between the scores was not statistically significant. ABC score of 2 or greater was 75% sensitive and 86% specific for predicting MT (correctly classified 85%). The ABC score, which uses nonlaboratory, nonweighted parameters, is a simple and accurate in identifying patients who will require MT as compared with those previously published scores.


Social deprivation index and ischemic events after percutaneous coronary intervention in patients with diabetes mellitus.
The aim of this study was to assess neighborhood-based differences in outcomes of diabetics versus non-diabetics undergoing percutaneous coronary interventions. Disparities in healthcare access impact long-term outcomes in safety net populations. Diabetes mellitus (DM) is associated with worse clinical outcomes in patients with coronary artery disease (CAD) and may disproportionately impact patients with CAD from underserved populations. We created a geocoded retrospective cohort of patients who underwent percutaneous coronary intervention (PCI) at an urban safety net hospital in this single-center cohort analysis. We evaluated long-term ischemic events in diabetics versus nondiabetics through review of electronic medical records. Social deprivation index (SDI) was calculated based on US-census tract level and stratified according to quintiles. Among 1002 patients, 46% (n = 463) were diabetic and among those 48% (n = 222) were in the highest quintile of SDI. Baseline and angiographic characteristics were similar among diabetic and nondiabetic subjects. Among diabetic patients, those in the highest SDI quintile had significantly higher risk of cardiovascular death and myocardial infarction as compared to those in the remaining quintiles (log rank: p = 0.029) (adjusted hazard's ratio: 1.72 [95% CI: 1.01-2.92], p = 0.04). There was no association of the SDI with outcomes in nondiabetic patients (log rank: p = 0.39). In an underserved population, patients with diabetes and high SDI demonstrate higher rates of adverse ischemic events and cardiovascular death during long-term follow up after PCI. Further research examining the impact of disparities in healthcare access on outcomes after PCI in patients with diabetes is warranted.


Rheological microscopy: local mechanical properties from microrheology.
We demonstrate how tracer microrheology methods can be extended to study submicron scale variations in the viscoelastic response of soft materials; in particular, a semidilute solution of lambda-DNA. The polymer concentration is depleted near the surfaces of the tracer particles, within a distance comparable to the polymer correlation length. The rheology of this microscopic layer alters the tracers' motion and can be precisely quantified using one- and two-point microrheology. Interestingly, we found this mechanically distinct layer to be twice as thick as the layer of depleted concentration, likely due to solvent drainage through the locally perturbed polymer structure.


Cardiovascular optoacoustics: From mice to men - A review.
Imaging has become an indispensable tool in the research and clinical management of cardiovascular disease (CVD). An array of imaging technologies is considered for CVD diagnostics and therapeutic assessment, ranging from ultrasonography, X-ray computed tomography and magnetic resonance imaging to nuclear and optical imaging methods. Each method has different operational characteristics and assesses different aspects of CVD pathophysiology; nevertheless, more information is desirable for achieving a comprehensive view of the disease. Optoacoustic (photoacoustic) imaging is an emerging modality promising to offer novel information on CVD parameters by allowing high-resolution imaging of optical contrast several centimeters deep inside tissue. Implemented with illumination at several wavelengths, multi-spectral optoacoustic tomography (MSOT) in particular, is sensitive to oxygenated and deoxygenated hemoglobin, water and lipids allowing imaging of the vasculature, tissue oxygen saturation and metabolic or inflammatory parameters. Progress with fast-tuning lasers, parallel detection and advanced image reconstruction and data-processing algorithms have recently transformed optoacoustics from a laboratory tool to a promising modality for small animal and clinical imaging. We review progress with optoacoustic CVD imaging, highlight the research and diagnostic potential and current applications and discuss the advantages, limitations and possibilities for integration into clinical routine.


Sequence of lethal events in HeLa cells exposed to the G2 blocking cytolethal distending toxin.
The bacterial cytolethal distending toxin (CDT) was previously shown to block the cell cycle of several cell lines at stage G2 through inactivation of the cyclin-dependent kinase Cdkl and without induction of DNA strand breaks. In the present study, we have analyzed, using various methods of analytical cytometry, the progressive transformation and delayed lethal events in the tumor-derived HeLa cell line temporarily exposed to CDT. The cell proliferation arrest induced by CDT was irreversible but, starting about two days after exposure, the G2 block released partially, concomitantly with a decline in the level of Cdkl phosphorylation. This partial release resulted in endoreduplication, leading to the emergence of a significant subpopulation of cells with a 8C DNA content, and by multipolar abortive mitosis which accounted for the mortality recorded 2 and 3 days after exposure. The other major lethal event was a micronucleation process which started to be significant about 3 days after exposure and amplified later on. Both multipolar abortive mitosis and micronucleation appeared topologically related to centrosomal amplification.


Gene expression changes with differentiation of cord blood stem cells to respiratory epithelial cells: a preliminary observation.
Owing to wide availability, low cost and avoidance of ethical concerns, umbilical cord blood (UCB) provides an attractive source of stem cells for investigational and therapeutic uses. In this study, we sought to characterize the gene expression changes as stem cells from UCB differentiate toward alveolar type II pneumocytes (ATII). Control and experimental cells were cultured in maintenance medium (mesenchymal stem cell growth medium) or differentiation medium (small airway growth medium (SAGM)), respectively, for 8 days. Total RNA was isolated from control and experimental groups for gene expression profiling and real-time polymerase chain reaction assay. Analysis of only mixed cell lines (n = 2) with parameters including a P value of 0.01 and an intergroup gap of 2.0 yielded a set of 373 differentially expressed genes. Prominently upregulated genes included several genes associated with ATII cells and also lung cancers: ALDH3A1, VDR and CHKA. Several upregulated genes have been shown to be integral or related to ATII functioning: SGK1, HSD17B11 and LEPR. Finally, several upregulated genes appear to play a role in lung cancers, including FDXR and GP96. Downregulated genes appear to be associated with bone, muscle and central nervous system tissues as well as other widespread tissues. To the best of our knowledge, this accounting of the gene expression changes associated with the differentiation of a human UCB-derived stem cell toward an ATII cell represents the first such effort. Dissecting which components of SAGM affect specific gene regulation events is warranted.


Forced bonding and QTAIM deficiencies: a case study of the nature of interactions in He@adamantane and the origin of the high metastability.
Calculations within the framework of the interacting quantum atoms (IQA) approach have shown that the interactions of the helium atom with both tertiary, tC, and secondary, sC, carbon atoms in the metastable He@adamantane (He@adam) endohedral complex are bonding in nature, whereas the earlier study performed within the framework of Bader's quantum theory of atoms in molecules (QTAIM) revealed that only He---tC interactions are bonding. The He---tC and He---sC bonding interactions are shown to be forced by the high pressure that the helium and carbon atoms exert upon each other in He@adam. The occurrence of a bonding interaction between the helium and sC atoms, which are not linked by a bond path, clearly shows that the lack of a bond path between two atoms does not necessarily indicate the lack of a bonding interaction, as is asserted by QTAIM. IQA calculations showed that not only the destabilization of the adamantane cage, but also a huge internal destabilization of the helium atom, contribute to the metastability of He@adam, these contributions being roughly equal. This result disproves previous opinions based on QTAIM analysis that only the destabilization of the adamantane cage accounts for the endothermicity of He@adam. Also, it was found that there is no homeomorphism of the ρ(r) and -v(r) fields of He@adam. Comparison of the IQA and QTAIM results on the interactions in He@adam exposes other deficiencies of the QTAIM approach. The reasons for the deficiencies in the QTAIM approach are analyzed.


Friction control with nematic lubricants via external fields.
We study the connection between sliding friction and the phase behavior of a simple rigid bead-necklace model of a liquid crystal (LC) lubricant layer confined between two parallel plates. The dynamics is dependent on competing LC ordering mechanisms, including the direction of sliding, and an applied (electric) field. Together with temperature and an applied pressure, determining whether the lubricant is in a fluidlike isotropic state or in a layered in-plane nematic state, such ordering is found to control the frictional properties of the lubricant. Our extensive molecular dynamics simulations reveal in a detailed manner how friction can be controlled via applied fields. The results are expected to help in designing novel strategies to develop lubricants with dynamically controllable properties.


Cyclic nucleotide-gated ion channels.
Cyclic nucleotide-gated (CNG) channels are nonselective cation channels first identified in retinal photoreceptors and olfactory sensory neurons (OSNs). They are opened by the direct binding of cyclic nucleotides, cAMP and cGMP. Although their activity shows very little voltage dependence, CNG channels belong to the superfamily of voltage-gated ion channels. Like their cousins the voltage-gated K+ channels, CNG channels form heterotetrameric complexes consisting of two or three different types of subunits. Six different genes encoding CNG channels, four A subunits (A1 to A4) and two B subunits (B1 and B3), give rise to three different channels in rod and cone photoreceptors and in OSNs. Important functional features of these channels, i.e., ligand sensitivity and selectivity, ion permeation, and gating, are determined by the subunit composition of the respective channel complex. The function of CNG channels has been firmly established in retinal photoreceptors and in OSNs. Studies on their presence in other sensory and nonsensory cells have produced mixed results, and their purported roles in neuronal pathfinding or synaptic plasticity are not as well understood as their role in sensory neurons. Similarly, the function of invertebrate homologs found in Caenorhabditis elegans, Drosophila, and Limulus is largely unknown, except for two subunits of C. elegans that play a role in chemosensation. CNG channels are nonselective cation channels that do not discriminate well between alkali ions and even pass divalent cations, in particular Ca2+. Ca2+ entry through CNG channels is important for both excitation and adaptation of sensory cells. CNG channel activity is modulated by Ca2+/calmodulin and by phosphorylation. Other factors may also be involved in channel regulation. Mutations in CNG channel genes give rise to retinal degeneration and color blindness. In particular, mutations in the A and B subunits of the CNG channel expressed in human cones cause various forms of complete and incomplete achromatopsia.


Factors affecting clinical pregnancy rates after IUI for the treatment of unexplained infertility and mild male subfertility.
The aim of the present retrospective study was to evaluate intrauterine insemination (IUI) clinical experiences and to define the variables for predicting success. The present study was an observational trial performed in a private IVF center on subfertile couples who had applied for treatment between 2002 and 2012, in which the data of 503 IUI cases were retrospectively reviewed. Couples who had been diagnosed with unexplained and mild male subfertility were included. The primary outcome measure was the clinical pregnancy rate in an attempt to form a predictive model for the odds of a clinical pregnancy. Recorded parameters were used to determine the prediction model. Utilizing univariate logistic regression analysis, clinical pregnancy was positively associated with the duration of infertility (OR=1.09, p=0.089), secondary infertility (OR=1.77, p=0.050), and +4 sperm motility after preparation (OR=1.03, p=0.091). Following an adjustment analysis involving a multivariate logistic regression, clinical pregnancy was still found to positively associate with secondary infertility (OR=2.51, p=0.008). IUI success in secondary infertile couples who were in the unexplained infertility and mild male subfertility groups was higher than that in primary infertile couples, and the chances of pregnancy increased as sperm numbers with +4 motility increased. It is difficult to concomitantly evaluate all these parameters and to determine a predictive parameter in IUI independent from other factors.


Conserved beta-hairpin recognition by the GYF domains of Smy2 and GIGYF2 in mRNA surveillance and vesicular transport complexes.
The yeast suppressor of myosin 2 protein (Smy2) interacts with mRNA-processing proteins through recognition of proline-rich sequences (PRS). Here, we describe the crystal structure of the GYF domain of Smy2 in association with a PRS from the yeast branch point binding protein (BBP/ScSF1). Complex formation requires that the beta-hairpin of the central PPGL motif of the ligand is accommodated by an extended hydrophobic cleft in the domain-a specificity feature that is maintained in the human protein GIGYF2. SILAC/MS experiments in combination with PRS site inhibition show that Smy2 associates with the Ccr4-NOT deadenylase complex, whereas GIGYF2 interacts not only with mRNA surveillance factors, but also with vesicular transport proteins and Atrophin-1. GIGYF2 is shown to associate with COPII-vesicle proteins and localize to the ER and Golgi in resting cells, whereas environmental challenge drives GIGYF2 into stress granules. The current study highlights the structural basis for PRS recognition by Smy2-type GYF domains, and implicates Smy2 and GIGYF2 in both mRNA processing and the secretory pathway.


Mercury exposure in a high fish eating Bolivian Amazonian population with intense small-scale gold-mining activities.
Methylmercury exposure in Amazonian communities through fish consumption has been widely documented in Brazil. There is still a lack of data in other Amazonian countries, which is why we conducted this study in the Bolivian Amazon basin. Simple random sampling was used from a small village located in the lower Beni River, where there is intense gold mining and high fish consumption. All participants were interviewed and hair samples were taken to measure total mercury concentrations. The hair mercury geometric mean in the general population was 3.02 microg/g (CI: 2.69-3.37; range: 0.42-15.65). Age and gender were not directly associated with mercury levels. Fish consumption showed a positive relation and so did occupation, especially small-scale gold mining. Hair mercury levels were lower than those found in Brazilian studies, but still higher than in non-exposed populations. It is necessary to assess mercury exposure in the Amazonian regions where data is still lacking, using a standardized indicator.


Breast cancer in octogenarian women: clinical characteristics and outcome.
Breast cancer incidence increases in the elderly but data on treatment and outcomes of elderly patients is limited. We assessed the clinicopathological features and outcomes of our patients with breast cancer aged ≥80 years in comparison with their younger postmenopausal counterparts. The records of 83 patients diagnosed with breast cancer after the age of 80 (group 1) between 2003 and 2011 in 4 different centers were retrospectively evaluated and the clinicopathological features and outcomes were assessed in comparison with a control group (group 2) of 249 patients aged between 60-70 years. Median ages at diagnosis were 82 years (range 80-95) and 64 years (range 60-70) for group 1 and group 2, respectively. The incidence of invasive cancers other than ductal or lobular type was higher in group 1 than in group 2 (20 vs 8%; p=0.0177rpar;. More patients in group 1 had Charlson Comorbidty scores ≥1 than those in group 2 (49 vs 36%; p=0.011). Patients in group 1 had more conservative operations and less axillary node dissections (ALND) and they received chemotherapy, trastuzumab or radiotherapy less frequently compared to their younger counterparts in group 2. Median follow up period was 36 months (range 1-178) in group 1 and 24 months (range 12-217) in group 2. Five-year disease free survival (DFS) was 53.7 and 75.9) (p=0.005), 5-year overall survival (OS) was 61.9% and 80.47percnt; in group 1 and group 2 (p=0.001), respectively. Advanced stage (stage IV vs stage I, II, III, p=0.051) and cerbB2 positivity (p<0.001) were found to be associated with shorter DFS in patients ≥80 years of age. Although the majority of patients were undertreated in our study according to the current guidelines, mortality rates were quite low. Different biology of the disease in the elderly might explain this difference.


Injection of immature dendritic cells into adjuvant-treated skin obviates the need for ex vivo maturation.
A key and limiting step in the process of generating human monocyte-derived dendritic cells (DC) for clinical applications is maturation. In the setting of immunotherapy, DC are matured ex vivo by culturing them with various agents that mimic the conditions encountered at a site of inflammation. This study examined whether the ex vivo DC maturation step could be replaced by maturing DC in situ by injecting immature DC into sites pre-exposed to agents that induce a microenvironment conducive to in situ maturation of the injected DC. The hypothesis was that recapitulation of the physiological conditions occurring during pathogen infection would lead to optimal conditions for DC maturation, migration, and function. Murine immature DC injected into adjuvant (Adjuprime, poly-arginine, or Imiquimod)-pretreated skin exhibited lymph node migratory capacity comparable to and immunostimulatory capacity equal to or exceeding that of ex vivo matured DC. Acquisition of migratory capacity did not always correlate with enhanced immunostimulatory capacity. Immunostimulatory capacity was not enhanced when mature DC were injected into adjuvant-pretreated sites and remained below that seen with immature DC matured in situ. Immature DC injected into adjuvant-pretreated sites were more effective than mature DC in stimulating antitumor immunity in mice. (111)Indium-labeled human monocyte-derived immature DC injected into adjuvant (Imiquimod)-pretreated sites in cancer patients acquired lymph node migratory capacity comparable to ex vivo matured DC. This study shows that in situ maturation offers a simpler and potentially superior method to generate potent immunostimulatory DC for clinical immunotherapy.


Evolution of ciprofloxacin-resistant Staphylococcus aureus in in vitro pharmacokinetic environments.
The development of novel antibacterial agents is decreasing despite increasing resistance to presently available agents among common pathogens. Insights into relationships between pharmacodynamics and resistance may provide ways to optimize the use of existing agents. The evolution of resistance was examined in two ciprofloxacin-susceptible Staphylococcus aureus strains exposed to in vitro-simulated clinical and experimental ciprofloxacin pharmacokinetic profiles for 96 h. As the average steady-state concentration (C(avg ss)) increased, the rate of killing approached a maximum, and the rate of regrowth decreased. The enrichment of subpopulations with mutations in grlA and low-level ciprofloxacin resistance also varied depending on the pharmacokinetic environment. A regimen producing values for C(avg ss) slightly above the MIC selected resistant variants with grlA mutations that did not evolve to higher levels of resistance. Clinical regimens which provided values for C(avg ss) intermediate to the MIC and mutant prevention concentration (MPC) resulted in the emergence of subpopulations with gyrA mutations and higher levels of resistance. A regimen producing values for C(avg ss) close to the MPC selected grlA mutants, but the appearance of subpopulations with higher levels of resistance was diminished. A regimen designed to maintain ciprofloxacin concentrations entirely above the MPC appeared to eradicate low-level resistant variants in the inoculum and prevent the emergence of higher levels of resistance. There was no relationship between the time that ciprofloxacin concentrations remained between the MIC and the MPC and the degree of resistance or the presence or type of ciprofloxacin-resistance mutations that appeared in grlA or gyrA. Regimens designed to eradicate low-level resistant variants in S. aureus populations may prevent the emergence of higher levels of fluoroquinolone resistance.


[Control of cisplatin-induced delayed emesis].
Despite excellent control of acute-stage emesis, some patients are still bothered by delayed emesis occurring more than 24 hours after cisplatin administration. We report 19 patients with 61 courses of cisplatin-based chemotherapy. They all received high-dose metoclopramide, dexamethasone and lorazepam on the day of cisplatin treatment. After 24 hours, they were treated with intravenous dexamethasone 8 mg once and metoclopramide 50 mg twice on day 2, and oral metoclopramide 10 mg qid on days 3-5. Delayed vomiting and nausea were noted in 27.9% and 39.4% respectively, as compared with 69.8% of delayed emesis and 79.4% of delayed nausea in 63 courses of 15 patients without receiving any antiemetics on days 2-5. The statistics showed significant difference (both P less than 0.001). Side effects were mild and acceptable. Therefore, this regimen is highly effective in preventing delayed vomiting and nausea.


Nucleotide sequence of the aacC3 gene, a gentamicin resistance determinant encoding aminoglycoside-(3)-N-acetyltransferase III expressed in Pseudomonas aeruginosa but not in Escherichia coli.
A chromosomal gentamicin resistance determinant from Pseudomonas aeruginosa was cloned on a 2.4-kb fragment in the broad-host-range vector pLAFR3. Substrate profiles for eight aminoglycosides at three concentrations showed that resistance was due to aminoglycoside-(3)-N-acetyltransferase III. This enzyme was produced in Pseudomonas strains but not in an Escherichia coli strain bearing the aacC3 gene. Nucleotide sequencing revealed two contiguous open reading frames (ORFs) preceded by a potential promoter and a ribosome-binding site. ORF-1 was 642 bp in length and encoded a protein of unknown function with a molecular mass of 23.9 kDa. ORF-2 was 813 bp in length and encoded a protein of 29.6 kDa. From deletion mutagenesis, in vitro transcription-translation data, and protein analysis of bacterial lysates, it was inferred that this 29.6-kDa protein represents the aminoglycoside-(3)-N-acetyltransferase III enzyme. A polymerase chain reaction with two specific intragenic 20-mer primers was developed to detect the aacC3 gene. A BstEII restriction site in the amplified DNA region was used to demonstrate the specificity of the reaction. Tests of 23 reference strains, which produced 12 different aminoglycoside-modifying enzymes, confirmed the specificities of the primers. The gene proved to be absent from a collection of 50 gentamicin-resistant P. aeruginosa strains selected at random in The Netherlands.


Measurement of dietary intake in the UNC Alumni Heart Study. University of North Carolina.
Research needs to identify diet and disease associations to provide direction about effecting change in individuals with dietary behaviors that increase risk of chronic disease. Inclusion of dietary assessment in the University of North Carolina Alumni Heart Study (UNCAHS) provides the opportunity to prospectively investigate dietary intake and chronic disease associations with measures of personality and behavioral risk factors. Development of the UNCAHS food frequency questionnaire and nutrient intake of 4,443 middle-aged men and women is provided stratified by total fat and vitamin A intake within demographic and health behavior categories. Alumni consume diets close to that recommended by current dietary guidelines. Both men and women have low calcium intake. Thirty-nine percent of the alumni consume diets with 30% of kilocalories from fat or less and 88% meet the RDA for vitamin A. Never smokers had lower fat diets and greater intakes of vitamin A than former or current smokers. Over 54% of alumni currently took vitamin/mineral supplements. UNCAHS participants will be tracked as they approach older ages with apparently less risk for diet-related chronic diseases than many Americans. The psychosocial correlates of these eating behaviors will be evaluated as disease endpoints occur.


Sorption of inorganic and total phosphorus from dairy and swine slurries to soil.
Understanding P sorption from animal manures is essential to formulate best management practices with regard to land application of manure from the standpoint of crop production and environmental quality. Little research has focused on the construction of P sorption isotherms where the P source is manure. The objectives of this study were to: (i) develop a procedure to characterize how inorganic P (P(i)) and total P (P(t)) from dairy slurry and swine slurry sorbs to soil; and (ii) compare the sorption characteristics of P(i) and P(t) where the P source was dairy slurry, swine slurry, or potassium phosphate (KH2PO4). Sorption solutions were prepared in 0.1 M KCl at pH 6 and equilibrated with soils at a 1:25 (w/v) soil/solution ratio for 24 h. Inorganic P, P(t), Al, and Fe in the equilibrated solutions were measured. For all soils, P(i) and P(t) sorption capacity of dairy slurry was greater than KH2PO4. Total P sorption capacity of swine slurry was greater than KH2PO4, while P(i) sorption capacity was less than KH2PO4. Overall, P(i) and P(t) sorption strengths of the manure slurries were less than or equal to KH2PO4. Increased P(i) sorption from dairy slurry was correlated with Fe and Al desorption. Reduction of P(i) sorption capacity from swine slurry was related to preferential sorption of organic P. Additional studies need to be conducted to determine how differences in P sorption between manures and fertilizer impact in-field P availability to a crop and potential for losses in runoff water.


Correlation of nuclear morphometry with progression of breast cancer.
Alterations in nuclear structure are the morphologic hallmark of cancer diagnosis. Nuclear size, shape, chromatin pattern, and nucleolar size and number have all been reported to change in breast cancer. Attempts to quantify nuclear alterations to establish grading systems, predict prognosis, and/or set guidelines for therapy have met with varied success. Therefore, the authors quantified the changes that occur with breast cancer with nuclear morphology in several different groups of patients: normal controls, intraductal carcinoma, invasive ductal carcinoma with negative nodes at mastectomy, and invasive ductal carcinoma with positive lymph nodes. Pleomorphism as measured by both nuclear area and intrasample variation increased with invasive histology and metastatic breast cancer. It is still unclear whether node-negative Stage II breast cancer requires adjuvant therapy. This issue would be less complicated if it were possible to identify those women at high risk of recurrence. Therefore, the authors retrospectively identified 30 women with node-negative Stage II infiltrating ductal carcinoma with a long follow-up period of 6 to 12 years. Computer-assisted morphometry of nuclei in routine hematoxylin and eosin-stained pathologic slides was done using the DynaCell Analysis System in a blinded fashion. DynaCell measures 15 nuclear parameters, including perimeter, area volume, roundness, and ellipticity. Although nuclear area and variance were related to breast cancer progression, nuclear morphometry did not predict successfully which patients would have recurrent disease in the women with Stage II, node-negative lesions at the time of mastectomy.


Maternal smoking and the risk of polyhydramnios.
Washington State birth certificates were used to conduct a population-based case-control study to assess the possible association of maternal smoking with polyhydramnios. All singleton births complicated by polyhydramnios (n = 557) were identified from the vital records for the years 1984 to 1987. For comparison, 1671 records were randomly selected for the same years from singleton births uncomplicated by polyhydramnios. Women who reportedly smoked prenatally were found to be at increased risk for polyhydramnios (relative risk [RR] = 1.7, 95% confidence interval [CI] = 1.5-2.1, adjusted for marital status, maternal age, and parity). When women with conditions known to be associated with polyhydramnios were excluded, the risk for those who smoked prenatally remained elevated (RR = 1.8, 95% CI = 1.1-2.3). Overdistention of the uterus from polyhydramnios may cause a variety of pregnancy complications. The observed association of smoking with polyhydramnios may be a further indication for public health interventions aimed at preventing smoking during pregnancy.


2D Hybrid Perovskites Employing an Organic Cation Paired with a Neutral Molecule.
Two-dimensional (2D) hybrid perovskites harness the chemical and structural versatility of organic compounds. Here, we explore 2D perovskites that incorporate both a first organic component, a primary ammonium cation, and a second neutral organic module. Through the experimental examination of 42 organic pairs with a range of functional groups and organic backbones, we identify five crystallization scenarios that occur upon mixing. Only one leads to the cointercalation of the organic modules with distinct and extended interlayer spacing, which is observed with the aid of X-ray diffraction (XRD) pattern analysis combined with cross-sectional transmission electron microscopy (TEM) and elemental analysis. We present a picture in which complementary pairs, capable of forming intermolecular bonds, cocrystallize with multiple structural arrangements. These arrangements are a function of the ratio of organic content, annealing temperature, and substrate surface characteristics. We highlight how noncovalent bonds, particularly hydrogen and halogen bonding, enable the influence over the organic sublattice in hybrid halide perovskites.


Haemoglobin D Punjab. Interaction with alpha thalassaemia and diagnosis by gene mapping.
A family which illustrates the inheritance of Hb D Punjab (a beta globin chain variant) and alpha thalassaemia is described. Interaction between Hb D Punjab and alpha thalassaemia is observed since levels of Hb D vary according to the number of alpha globin genes deleted. The technique of gene mapping has been utilised in the current study to provide definitive evidence of alpha thalassaemia and also demonstrates a novel way to identify Hb D Punjab.


Reactive oxygen species in the signaling and adaptation of multicellular microbial communities.
One of the universal traits of microorganisms is their ability to form multicellular structures, the cells of which differentiate and communicate via various signaling molecules. Reactive oxygen species (ROS), and hydrogen peroxide in particular, have recently become well-established signaling molecules in higher eukaryotes, but still little is known about the regulatory functions of ROS in microbial structures. Here we summarize current knowledge on the possible roles of ROS during the development of colonies and biofilms, representatives of microbial multicellularity. In Saccharomyces cerevisiae colonies, ROS are predicted to participate in regulatory events involved in the induction of ammonia signaling and later on in programmed cell death in the colony center. While the latter process seems to be induced by the total ROS, the former event is likely to be regulated by ROS-homeostasis, possibly H(2)O(2)-homeostasis between the cytosol and mitochondria. In Candida albicans biofilms, the predicted signaling role of ROS is linked with quorum sensing molecule farnesol that significantly affects biofilm formation. In bacterial biofilms, ROS induce genetic variability, promote cell death in specific biofilm regions, and possibly regulate biofilm development. Thus, the number of examples suggesting ROS as signaling molecules and effectors in the development of microbial multicellularity is rapidly increasing.


Recurrent deletion of ZNF630 at Xp11.23 is not associated with mental retardation.
ZNF630 is a member of the primate-specific Xp11 zinc finger gene cluster that consists of six closely related genes, of which ZNF41, ZNF81, and ZNF674 have been shown to be involved in mental retardation. This suggests that mutations of ZNF630 might influence cognitive function. Here, we detected 12 ZNF630 deletions in a total of 1,562 male patients with mental retardation from Brazil, USA, Australia, and Europe. The breakpoints were analyzed in 10 families, and in all cases they were located within two segmental duplications that share more than 99% sequence identity, indicating that the deletions resulted from non-allelic homologous recombination. In 2,121 healthy male controls, 10 ZNF630 deletions were identified. In total, there was a 1.6-fold higher frequency of this deletion in males with mental retardation as compared to controls, but this increase was not statistically significant (P-value = 0.174). Conversely, a 1.9-fold lower frequency of ZNF630 duplications was observed in patients, which was not significant either (P-value = 0.163). These data do not show that ZNF630 deletions or duplications are associated with mental retardation.


Neoplasia of the extraperitoneal rectum and anus. The perineal dilemma.
A retrospective analysis was undertaken of 113 patients with biopsy-proven neoplasia of the extraperitoneal rectum and anus occurring between 1970 and 1975. Common initial symptoms included bleeding, constipation, and diarrhea; colon obstruction was the initial symptom in only ten cases. Adenocarcinoma occurred in 90 per cent of cases while lesions such as epidermoid cancer, carcinoid, and melanoma were encountered rarely. Operative treatment consisted of abdominoperineal resection (APR) in 60 cases, colostomy alone in 26 cases, anterior resection 13 cases, and electrocoagulation in four cases. Ten patients refused operative therapy. Of patients undergoing APR, 7 per cent died in the perioperative period. Postoperative morbidity included infection, impotence, bladder dysfunction, and perineal complications. The single most important factor contributing to this high morbidity was perineal wound management: 34 patients managed by the open method sustained a 47 per cent complication rate while the 26 patients with closed and adequately drained wounds had only a 15 per cent complication rate.


Robust identification of Parkinson's disease subtypes using radiomics and hybrid machine learning.
It is important to subdivide Parkinson's disease (PD) into subtypes, enabling potentially earlier disease recognition and tailored treatment strategies. We aimed to identify reproducible PD subtypes robust to variations in the number of patients and features. We applied multiple feature-reduction and cluster-analysis methods to cross-sectional and timeless data, extracted from longitudinal datasets (years 0, 1, 2 & 4; Parkinson's Progressive Marker Initiative; 885 PD/163 healthy-control visits; 35 datasets with combinations of non-imaging, conventional-imaging, and radiomics features from DAT-SPECT images). Hybrid machine-learning systems were constructed invoking 16 feature-reduction algorithms, 8 clustering algorithms, and 16 classifiers (C-index clustering evaluation used on each trajectory). We subsequently performed: i) identification of optimal subtypes, ii) multiple independent tests to assess reproducibility, iii) further confirmation by a statistical approach, iv) test of reproducibility to the size of the samples. When using no radiomics features, the clusters were not robust to variations in features, whereas, utilizing radiomics information enabled consistent generation of clusters through ensemble analysis of trajectories. We arrived at 3 distinct subtypes, confirmed using the training and testing process of k-means, as well as Hotelling's T2 test. The 3 identified PD subtypes were 1) mild; 2) intermediate; and 3) severe, especially in terms of dopaminergic deficit (imaging), with some escalating motor and non-motor manifestations. Appropriate hybrid systems and independent statistical tests enable robust identification of 3 distinct PD subtypes. This was assisted by utilizing radiomics features from SPECT images (segmented using MRI). The PD subtypes provided were robust to the number of the subjects, and features.


Obstructive Bezoars of the Small Bowel Treated with Coca-Cola Zero through a Long Intestinal Tube and Endoscopic Manipulation.
An 82-year-old Japanese man visited our hospital with abdominal fullness accompanied by lower abdominal pain. He presented with small bowel obstruction due to multiple diospyrobezoars. The bezoars were successfully removed without any surgical intervention by the administration of Coca-Cola Zero through a long intestinal tube and subsequent endoscopic manipulation. Such a combination may be the treatment of choice for small bowel obstruction due to bezoars.


Glucose and oxygen metabolism after penetrating ballistic-like brain injury.
Traumatic brain injury (TBI) is a major cause of death and disability in all age groups. Among TBI, penetrating traumatic brain injuries (PTBI) have the worst prognosis and represent the leading cause of TBI-related morbidity and death. However, there are no specific drugs/interventions due to unclear pathophysiology. To gain insights we looked at cerebral metabolism in a PTBI rat model: penetrating ballistic-like brain injury (PBBI). Early after injury, regional cerebral oxygen tension and consumption significantly decreased in the ipsilateral cortex in the PBBI group compared with the control group. At the same time point, glucose uptake was significantly reduced globally in the PBBI group compared with the control group. Examination of Fluorojade B-stained brain sections at 24 hours after PBBI revealed an incomplete overlap of metabolic impairment and neurodegeneration. As expected, the injury core had the most severe metabolic impairment and highest neurodegeneration. However, in the peri-lesional area, despite similar metabolic impairment, there was lesser neurodegeneration. Given our findings, the data suggest the presence of two distinct zones of primary injury, of which only one recovers. We anticipate the peri-lesional area encompassing the PBBI ischemic penumbra, could be salvaged by acute therapies.


Comparative analysis of de novo assemblers for variation discovery in personal genomes.
Current variant discovery approaches often rely on an initial read mapping to the reference sequence. Their effectiveness is limited by the presence of gaps, potential misassemblies, regions of duplicates with a high-sequence similarity and regions of high-sequence divergence in the reference. Also, mapping-based approaches are less sensitive to large INDELs and complex variations and provide little phase information in personal genomes. A few de novo assemblers have been developed to identify variants through direct variant calling from the assembly graph, micro-assembly and whole-genome assembly, but mainly for whole-genome sequencing (WGS) data. We developed SGVar, a de novo assembly workflow for haplotype-based variant discovery from whole-exome sequencing (WES) data. Using simulated human exome data, we compared SGVar with five variation-aware de novo assemblers and with BWA-MEM together with three haplotype- or local de novo assembly-based callers. SGVar outperforms the other assemblers in sensitivity and tolerance of sequencing errors. We recapitulated the findings on whole-genome and exome data from a Utah residents with Northern and Western European ancestry (CEU) trio, showing that SGVar had high sensitivity both in the highly divergent human leukocyte antigen (HLA) region and in non-HLA regions of chromosome 6. In particular, SGVar is robust to sequencing error, k-mer selection, divergence level and coverage depth. Unlike mapping-based approaches, SGVar is capable of resolving long-range phase and identifying large INDELs from WES, more prominently from WGS. We conclude that SGVar represents an ideal platform for WES-based variant discovery in highly divergent regions and across the whole genome.


A Review of Malaysian Medicinal Plants with Potential Anti-Inflammatory Activity.
This article aims to provide detailed information on Malaysian plants used for treating inflammation. An extensive search on electronic databases including PubMed, Google Scholar, Scopus, and ScienceDirect and conference papers was done to find relevant articles on anti-inflammatory activity of Malaysian medicinal plants. The keyword search terms used were "inflammation," "Malaysia," "medicinal plants," "mechanisms," "in vitro," and "in vivo." As a result, 96 articles on anti-inflammatory activity of Malaysian medicinal plants were found and further reviewed. Forty-six (46) plants (in vitro) and 30 plants (in vivo) have been identified to possess anti-inflammatory activity where two plants, Melicope ptelefolia (Tenggek burung) and Portulaca oleracea (Gelang pasir), were reported to have the strongest anti-inflammatory activity of more than 90% at a concentration of 250 µg/ml. It was showed that the activity was mainly due to the occurrence of diverse naturally occurring phytochemicals from diverse groups such as flavonoids, coumarins, alkaloids, steroids, benzophenone, triterpenoids, curcuminoids, and cinnamic acid. Hence, this current review is a detailed discussion on the potential of Malaysian medicinal plants as an anti-inflammatory agent from the previous studies. However, further investigation on the possible underlying mechanisms and isolation of active compounds still remains to be investigated.


Host-microbe interactions in distal airways: relevance to chronic airway diseases.
This article is the summary of a workshop, which took place in November 2013, on the roles of microorganisms in chronic respiratory diseases. Until recently, it was assumed that lower airways were sterile in healthy individuals. However, it has long been acknowledged that microorganisms could be identified in distal airway secretions from patients with various respiratory diseases, including cystic fibrosis (CF) and non-CF bronchiectasis, chronic obstructive pulmonary disease, asthma and other chronic airway diseases (e.g. post-transplantation bronchiolitis obliterans). These microorganisms were sometimes considered as infectious agents that triggered host immune responses and contributed to disease onset and/or progression; alternatively, microorganisms were often considered as colonisers, which were considered unlikely to play roles in disease pathophysiology. These concepts were developed at a time when the identification of microorganisms relied on culture-based methods. Importantly, the majority of microorganisms cannot be cultured using conventional methods, and the use of novel culture-independent methods that rely on the identification of microorganism genomes has revealed that healthy distal airways display a complex flora called the airway microbiota. The present article reviews some aspects of current literature on host-microbe (mostly bacteria and viruses) interactions in healthy and diseased airways, with a special focus on distal airways.


Transcutaneous electrical nerve stimulation for the control of pain during rehabilitation after total knee arthroplasty: A randomized, blinded, placebo-controlled trial.
This study evaluated the efficacy of transcutaneous electrical nerve stimulation (TENS) in reducing pain and hyperalgesia and increasing function after total knee arthroplasty (TKA). We hypothesized that participants using TENS during rehabilitation exercises would report significantly lower pain during range-of-motion (ROM) activity and fast walking but not at rest, would have less hyperalgesia, and would have better function than participants receiving placebo-TENS or standard care. We also hypothesized that change in ROM pain would differ based on psychological characteristics (trait anxiety, pain catastrophizing, and depression) and treatment group. This prospective, randomized study used intent-to-treat analyses in 317 participants after primary, unilateral TKA. Assessors, blinded to treatment allocation, measured pain, function (ROM and gait speed), and hyperalgesia (quantitative sensory tests) postoperatively and 6 weeks after surgery. Analgesic intake, anxiety, depression, and pain catastrophizing were also assessed. TENS participants used it 1 to 2 times per day at 42 mA (on average) and had less pain postoperatively during active knee extension (P=.019) and fast walking (P=.006) than standard care participants. TENS and placebo-TENS were not significantly different. TENS participants who scored low on anxiety and pain catastrophizing had a greater reduction in ROM pain at 6 weeks than those who scored high on these factors (P=.002 and P=.03). Both TENS and placebo-TENS participants had less postoperative mechanical hyperalgesia (P=.03-.01) than standard care participants. Supplementing pharmacologic analgesia with TENS during rehabilitation exercises reduces movement pain postoperatively, but a placebo influence exists and the effect is gone by 6 weeks. Patients with low anxiety and pain catastrophizing may benefit most from TENS.


Effect of Dietary Coenzyme Q10 Plus NADH Supplementation on Fatigue Perception and Health-Related Quality of Life in Individuals with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Prospective, Randomized, Double-Blind, Placebo-Controlled Trial.
Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, multisystem, and profoundly debilitating neuroimmune disease, probably of post-viral multifactorial etiology. Unfortunately, no accurate diagnostic or laboratory tests have been established, nor are any universally effective approved drugs currently available for its treatment. This study aimed to examine whether oral coenzyme Q10 and NADH (reduced form of nicotinamide adenine dinucleotide) co-supplementation could improve perceived fatigue, unrefreshing sleep, and health-related quality of life in ME/CFS patients. A 12-week prospective, randomized, double-blind, placebo-controlled trial was conducted in 207 patients with ME/CFS, who were randomly allocated to one of two groups to receive either 200 mg of CoQ10 and 20 mg of NADH (n = 104) or matching placebo (n = 103) once daily. Endpoints were simultaneously evaluated at baseline, and then reassessed at 4- and 8-week treatment visits and four weeks after treatment cessation, using validated patient-reported outcome measures. A significant reduction in cognitive fatigue perception and overall FIS-40 score (p < 0.001 and p = 0.022, respectively) and an improvement in HRQoL (health-related quality of life (SF-36)) (p < 0.05) from baseline were observed within the experimental group over time. Statistically significant differences were also shown for sleep duration at 4 weeks and habitual sleep efficiency at 8 weeks in follow-up visits from baseline within the experimental group (p = 0.018 and p = 0.038, respectively). Overall, these findings support the use of CoQ10 plus NADH supplementation as a potentially safe therapeutic option for reducing perceived cognitive fatigue and improving the health-related quality of life in ME/CFS patients. Future interventions are needed to corroborate these clinical benefits and also explore the underlying pathomechanisms of CoQ10 and NADH administration in ME/CFS.


Case study: Biochemistry without borders: a case study utilising infographics.
The present paper addresses a case study on the implementation of an online learning exercise utilising infographics in undergraduate Biochemistry and General Chemistry courses at the University of Roehampton (UoR) and Hostos Community College (HCC) of the City University of New York (CUNY). Students at UoR were asked to create infographics on topics related to the four major classes of biomolecules: carbohydrates, lipids, proteins and nucleic acids, and these infographics were shared with HCC students in an active learning exercise which incorporated peer evaluation and feedback. We highlight the various teaching and learning strategies, as well as the challenges related to the implementation of digital tools, in the educational process during the COVID-19 pandemic to maintain student engagement and active learning. Student feedback revealed positive learning gains on biochemistry concepts related to the four biomolecules. The exercise was viewed favourably by students, with learners indicating the acquisition of digital skills to effectively represent and visualise their understanding of biochemical concepts and explain these processes to peers.


Impact of diagnostic bone biopsies on the management of non-vertebral osteomyelitis: A retrospective cohort study.
Optimal antibiotic management of patients with osteomyelitis remains a challenge for many clinicians. Although image-guided bone biopsy (IGB) remains the gold standard, its role in confirming diagnosis and guiding antibiotic management is not clear in patients with non-vertebral osteomyelitis.To determine the diagnostic yield of IGB and its impact on antibiotic management in non-vertebral osteomyelitis.Retrospective cohort study.Urban academic medical center.Patients admitted for non-vertebral osteomyelitis who underwent image-guided bone biopsy.Primary outcomes were microbiologic and histopathological results. We evaluated the impact of IGB on clinician-initiated changes in antibiotic regimen before and after biopsy.We evaluated 203 bone biopsies in 185 patients with clinical suspicion of osteomyelitis. 79% of patient received antibiotics prior to biopsy. Bone cultures were positive in 28% and histopathology confirmed osteomyelitis in 29%, but concordance was poor. Furthermore, clinical suspicion of infection was much higher, given that 68% received empiric antibiotics. Leukocytosis was significantly associated with positive cultures in multivariate analysis. There was no statistically significant correlation between antibiotic management and bone culture results. When culture yielded an organism, empiric regimens were kept the same, broadened or narrowed with equal frequency; targeted regimens were chosen only in 4 cases. Despite negative cultures in 98/138 cases having received empiric treatment, antibiotics were discontinued in only 8 cases. Even when empiric treatment was not given, negative cultures did not dissuade clinicians from eventual antibiotic use in a significant number of cases (17/48). In 46/71 patients whose final regimen included vancomycin, there was no evidence of current or past infection with MRSA.In patients with non-vertebral osteomyelitis, the diagnostic yield of image-guided bone biopsy is low, and clinicians frequently make decisions regarding antibiotic management that are not aligned with culture results.


Steady-state nonlinear pharmacokinetics of 5-fluorouracil during hepatic arterial and intravenous infusions in cancer patients.
Hepatic arterial catheters were placed for therapy in 8 patients with primary or metastatic liver cancer. Temporary hepatic venous catheters allowed direct sampling of blood for hepatic venous drug concentrations. Patients were administered from three to six infusions at rates of 10, 30, 90, 135, 180, 210, and 270 mg/kg/day (0.053 to 1.43 microM/kg/min), given over 2 h, of 5-fluorouracil (FUra). In Method 1, FUra was infused i.v., and FUra was measured in plasma from hepatic arterial and hepatic venous blood. In Method 2, FUra was given i.v. at one time and infused into hepatic arterial blood at another time, and FUra was measured in plasma from peripheral blood at the same site in both cases. Steady-state FUra plasma concentrations were measured by a sensitive and specific high-performance liquid chromatography method. Data were computer fitted to the equations appropriate for a physiological two-compartment flow model with Michaelis-Menten elimination from the peripheral compartment and blood flow rate, Q, between the central and peripheral compartment. Methods 1 and 2 gave mean Vmax and Km values which did not differ significantly; the overall mean Vmax was 2.02 microM/kg/min, and the overall mean Km was 10.9 microM. For Method 1 the mean Q1 value was 0.0803 liters/(kg X min) or 5.26 liters/min, which is the same as cardiac output, but for Method 2 the mean Q2 value was higher, namely 0.189 liters/(kg X min) or 13.0 liters/min. Steady-state systemic and intrinsic clearances and extraction ratios decreased progressively as the dose rate increased. Intra- and inter-subject variation of both Vmax and Km were of the same order of magnitude. As a result, dose rate escalation should be conservative for dose rates above 135 mg/kg/day. The results support hepatic arterial infusion as a means of improving the therapeutic index of FUra in the treatment of cancer of the liver.


A potential role for overdominance in the maintenance of colour variation in the Neotropical tortoise beetle, Chelymorpha alternans.
The presence of persistent polymorphisms within natural populations elicits the question of how such polymorphisms are maintained. All else equal, genetic drift and natural selection should remove genetic variants from populations. Disassortative mating and overdominance are potential mechanisms for maintaining variation within populations. Here, we consider the potential role of these mechanisms in maintaining variation in colour pattern in the tortoise beetle, Chelymorpha alternans. Five colour morphs distinguished by elytral and pronotal coloration are largely determined by a single locus of large effect with four segregating alleles. As many as four morphs co-occur in natural populations. We first assessed whether disassortative mating might maintain this polymorphism. To test for assortative and disassortative mating, we paired females with two males, one with the same colour pattern as the female and one with a different colour pattern and examined the colour patterns of the offspring. We found strong evidence for random mating as a function of colour pattern. We next assessed whether differences in offspring survival among assortative and disassortative male-female pairs maintain colour variation. Crosses involving disassortative pairings had significantly higher offspring survival during development and resulted in more adult progeny. This result is consistent with the effects of overdominance, whereby outcrossed individuals have higher fitness than their homozygous counterparts. Overall, differences in offspring survival appear to play a greater role in maintaining polymorphisms than nonrandom mating in species.


The relationship between sexual dimorphism and androgen response element proliferation in primate genomes.
In males of many vertebrate species, sexual selection has led to the evolution of sexually dimorphic traits, which are often developmentally controlled by androgen signaling involving androgen response elements (AREs). Evolutionary changes in the number and genomic locations of AREs can modify patterns of receptor regulation and potentially alter gene expression. Here, we use recently sequenced primate genomes to evaluate the hypothesis that the strength of sexual selection is related to the genome-wide number of AREs in a diversifying lineage. In humans, we find a higher incidence of AREs near male-biased genes and androgen-responsive genes when compared with randomly selected genes from the genome. In a set of primates, we find that gains or losses of AREs proximal to genes are correlated with changes in male expression levels and the degree of sex-biased expression of those genes. In a larger set of primates, we find that an increase in one indicator of sexual selection, canine size sexual dimorphism, is correlated with genome-wide ARE counts. Our results suggest that the responsiveness of the genome to androgens in humans and their close relatives has been shaped by sexual selection that arises from competition among males for mating access to females.


Higher levels of ethyl paraben and butyl paraben in rat amniotic fluid than in maternal plasma after subcutaneous administration.
Parabens are a group of antimicrobial preservatives widely used in cosmetics, pharmaceuticals, and in foods. Previous in vitro and in vivo studies have shown weak estrogenic effects of some parabens. Thus, especially, exposure of fetus and infants via the mother is a matter of concern. In order to obtain more knowledge about the distribution of ethyl paraben and butyl paraben in pregnant rats and pups after perinatal exposure, the presented study was designed. The data show response and distribution of ethyl paraben and butyl paraben in maternal rat plasma, pools of amniotic fluids, placenta, whole-body fetuses, and in fetal liver after dosing of dams with 100, 200, and 400 mg/kg body weight (bw)/day from gestational day 7 to 21. After cesarean section of dams, the fluids and tissues were collected, deconjugated, and purified by solid-phase extraction, and ethyl paraben and butyl paraben were analyzed by liquid chromatography-tandem mass spectrometry. Markedly higher levels of ethyl paraben compared to butyl paraben were found in all fluids and tissues. Both ethyl paraben and butyl paraben in maternal plasma, livers, and whole-body tissues from fetus seemed to be saturated after dosing with >or= 100 mg/kg bw/day, while both compounds were excreted into amniotic fluid in a dose-dependent manner. Significant difference was found between the level of ethyl paraben in maternal plasma and amniotic fluid after dosing with 200 mg/kg bw/day as well as between the levels of butyl paraben in maternal plasma and amniotic fluid after dosing with 100, 200, and 400 mg/kg bw/day.