Targeting metabolic vulnerabilities to overcome resistance to therapy in acute myeloid leukemia.
Malignant hematopoietic cells gain metabolic plasticity, reorganize anabolic mechanisms to improve anabolic output and prevent oxidative damage, and bypass cell cycle checkpoints, eventually outcompeting normal hematopoietic cells. Current therapeutic strategies of acute myeloid leukemia (AML) are based on prognostic stratification that includes mutation profile as the closest surrogate to disease biology. Clinical efficacy of targeted therapies, e.g., agents targeting mutant FMS-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenase 1 or 2, are mostly limited to the presence of relevant mutations. Recent studies have not only demonstrated that specific mutations in AML create metabolic vulnerabilities but also highlighted the efficacy of targeting metabolic vulnerabilities in combination with inhibitors of these mutations. Therefore, delineating the functional relationships between genetic stratification, metabolic dependencies, and response to specific inhibitors of these vulnerabilities is crucial for identifying more effective therapeutic regimens, understanding resistance mechanisms, and identifying early response markers, ultimately improving the likelihood of cure. In addition, metabolic changes occurring in the tumor microenvironment have also been reported as therapeutic targets. The metabolic profiles of leukemia stem cells (LSCs) differ, and relapsed/refractory LSCs switch to alternative metabolic pathways, fueling oxidative phosphorylation (OXPHOS), rendering them therapeutically resistant. In this review, we discuss the role of cancer metabolic pathways that contribute to the metabolic plasticity of AML and confer resistance to standard therapy; we also highlight the latest promising developments in the field in translating these important findings to the clinic and discuss the tumor microenvironment that supports metabolic plasticity and interplay with AML cells.


Development of neural repair therapy for chronic spinal cord trauma: soluble Nogo receptor decoy from discovery to clinical trial.
After traumatic spinal cord injury (SCI), neurological deficits persist due to the disconnection of surviving neurons. While repair of connectivity may restore function, no medical therapy exists today.This review traces the development of the neural repair-based therapeutic AXER-204 from animal studies to the recent clinical trial for chronic cervical SCI. Molecular studies reveal a Nogo-66 Receptor 1 (NgR1, RTN4R) pathway inhibiting axon regeneration, sprouting, and plasticity in the adult mammalian central nervous system (CNS). Rodent and nonhuman primate studies demonstrate that the soluble receptor decoy NgR(310)ecto-Fc or AXER-204 promotes neural repair and functional recovery in transection and contusion SCI. Recently, this biological agent completed a first-in-human and randomized clinical trial for chronic cervical SCI. The intervention was safe and well tolerated. Across all participants, upper extremity strength did not improve with treatment. However, posthoc and biomarker analyses suggest that AXER-204 may benefit treatment-naïve patients with incomplete SCI in the chronic stage. NgR1 signaling restricts neurological recovery in animal studies of CNS injury. The recent clinical trial of AXER-204 provides encouraging signals supporting future focused trials of this neural repair therapeutic. Further, AXER-204 studies provide a roadmap for the development of additional and synergistic therapies for chronic SCI.


Tumor necrosis factor-alpha up-regulation in spontaneously proliferating cells derived from bovine leukemia virus-infected cattle.
We previously reported that tumor necrosis factor alpha (TNF-alpha) was one of the cytokines that contributed to the leukemogenesis caused by bovine leukemia virus (BLV). To determine if the spontaneous cell proliferation observed in the late disease stages, such as persistent lymphocytosis and lymphosarcoma, correlated with the expression level of TNF-alpha, we analyzed the mRNA expression levels for TNF-alpha in spontaneously proliferating PBMCs derived from BLV-infected cattle. The mean mRNA expression level for TNF-alpha was higher in the spontaneously proliferating PBMCs derived from BLV-infected cattle than in non-spontaneously proliferating PBMCs from normal cattle. The TNF-alpha protein level in the PBMCs was determined by flow cytometric analysis, and it was noted that most of the cells expressing membrane-bound TNF-alpha in the spontaneously proliferating cells were CD5+ or sIgM+-cells. Additionally, in order to determine if this spontaneous proliferation can be blocked by anti-bovine TNF-alpha MAb, the spontaneously proliferating PBMCs from a BLV-infected cattle were cultured in the presence of the MAb. The addition of this MAb at the beginning of the 72 h-cultivation clearly inhibited spontaneous proliferation of cells in a dose-dependent manner, indicating the direct involvement of TNF-alpha in the spontaneous proliferation of PBMCs during the late disease stage. These data suggest that an aberrant expression of TNF-alpha might contribute to the progression of bovine leukosis in animals which develop persistent lymphocytosis of B-cells or B-cell lymphosarcoma.


IT in the ED: past, present, and future.
Over the past 40 years, information technology in the emergency department (ED) has evolved from primitive tracking, order entry, and laboratory reporting systems to complex multifunctional applications that permeate all aspects of patient care and ED operations. Spurred by incentive programs and technological improvements, both ED physicians and administrators view these systems as a way to increase staff efficiency, to improve patient care quality and safety, to satisfy compliance and reporting obligations, and to reduce costs. As organizations implement and optimize systems, it is helpful to look back at how these technologies were developed, to review the current impacts and effects of their use, and to glimpse the future of information technology in the ED.


The effect of vitamin D3 on the production of cytotoxic factors by human peripheral blood mononuclear cells.
Vitamin D3 at a concentration of 300 nM was shown to significantly reduce the yields of cytotoxin produced by human peripheral blood mononuclear cells. Reduction of cytotoxin titers occurred when induction was performed with either concanavalin A, interleukin 2, or ionomycin. Typing of this cytotoxin was accomplished using antisera that were prepared by immunization of rabbits with either recombinant tumor necrosis factor or lymphotoxin. Both antisera were demonstrated to neutralize the cytotoxic activity produced by the peripheral blood mononuclear cells in the presence or absence of vitamin D3. These latter experiments suggested that the cytotoxin in question might be lymphotoxin. Vitamin D3 was also shown to decrease cytotoxin production by a transformed B-cell line known to produce only lymphotoxin, supporting the concept that this vitamin could diminish yields of lymphotoxin at least under certain circumstances. However, purified adherent cells induced by Escherichia coli lipopolysaccharide produced a cytotoxin that was also inhibited by the presence of vitamin D3. Indomethacin failed to influence the effects of vitamin D3 on the production of the cytotoxin. These studies suggest that vitamin D3 may have a role in regulating the secretion of cytotoxic factors which may be important in the defense against neoplastic diseases.


Shear stress related hemolysis and its modelling by mechanical degradation of polymer solutions.
Human or animal blood is normally used as a test fluid for in vitro evaluation of hemolysis by artificial organs. However, blood has some disadvantages (no transparence for visualization of the flow field, large biological variability and problems with cleaning the devices). For that reason, it would be of advantage to have a reproducibile transparent technical fluid with blood like flow characteristics and that exhibits similar shear depending destruction. We have shown that solutions of long-chaining polymer molecules are destroyed by heart valve prostheses in a similar manner as blood corpuscules. In the presented study, a direct comparison between erythrocyte destruction of bovine blood and degradation of Polyacrylamid molecules in a 300 ppm solution is given. A uniform shear field was applied to the fluid using a plate-plate geometry shear device. This device allows a variation of shear stress and shear time in the range of 15-500 N/m2 and 64-516 ms, respectively A correlation between the index of hemolysis (ratio of free plasma hemoglobin to total hemoglobin) and the percentage viscosity decrease (derived from low shear viscosity at a shear rate of 0.01/s) was found. Thus, PAA solutions are suitable model fluids for in vitro estimation of the damaging effects of artificial devices.


A novel serine/proline-rich domain in combination with a transmembrane domain is required for the insertion of AtTic40 into the inner envelope membrane of chloroplasts.
AtTic40 is part of the chloroplastic protein import apparatus that is anchored in the inner envelope membrane by a single N-terminal transmembrane domain, and has a topology in which the bulk of the C-terminal domain is oriented toward the stroma. The targeting of AtTic40 to the inner envelope membrane involves two steps. Using an in vitro import assay, we showed that the sorting of AtTic40 requires a bipartite transit peptide, which was first cleaved by the stromal processing peptidase (SPP), thus generating a soluble AtTic40 stromal intermediate (iAtTic40). iAtTic40 was further processed by a second unknown peptidase, which generates its mature form (mAtTic40). Using deletion mutants, we identified a sequence motif N-terminal of the transmembrane domain that was essential for reinsertion of iAtTic40 into the inner envelope membrane. We have designated this region a serine/proline-rich (S/P-rich) domain and present a model describing its role in the targeting of AtTic40 to the inner envelope membrane.


E1B-55K-deleted adenovirus expressing E1A-13S by AFP-enhancer/promoter is capable of highly specific replication in AFP-producing hepatocellular carcinoma and eradication of established tumor.
Here, we constructed a recombinant replication-competent adenovirus (rRCAd; AdAFPep/Rep) that expresses both E1A-13S driven by the alpha-fetoprotein (AFP) enhancer/promoter (AFPep) lacking any silencers in the 5'-flanking region of the AFP gene, and 55K-deleted E1B driven by the cytomegalovirus (CMV) promoter. We then examined the feasibility of gene therapy utilizing this virus for AFP-producing hepatocellular carcinoma (HCC). AdAFPep/Rep lysed all the AFP-producing HCC cell lines (HuH7, HepG2, PLC/PRF/5 (P5)) examined at a multiplicity of infection (MOI) as low as 0.1 and did not lyse primary human hepatocytes (Hc) at a MOI as high as 100, indicating that the rRCAd virus can lyse AFP-producing HCC cells with a higher specificity and potency than previously reported. Furthermore, this virus was capable of complete eradication of a preestablished HuH7-cell tumor by a single intratumoral injection of 10(8) plaque-forming units (pfu) of AdAFPep/Rep. Thus, AdAFPep/Rep may be applicable for clinical use.


Big Hitters: Important Factors Characterizing Team Effectiveness in Professional Cricket.
While organizational psychology attests to the multidimensional nature of team effectiveness, insight regarding the most important factors contributing to the effectiveness of sports teams, especially elite teams, is lacking. An abductive method of qualitative enquiry was adopted to capture participants' construal of team effectiveness, drawing on the extant literature in both sport and organizational psychology. Semi-structured interviews were conducted with 21 players, coaches, and psychologists involved in elite cricket, with resultant data analyzed inductively initially, before being reanalyzed deductively. Although, the narratives endorsed the value of many of the deductively derived factors, other constructs more prominent in organizational psychology (e.g., trust and intra-group conflict) appeared to be more important than traditional sport psychology group factors. The results revealed six broad themes; culture and environment, values, communication, understanding, leadership, and unique individuals, with some gender differences apparent throughout. Based on our elite sample's construal of team effectiveness, we propose a new model representing a practical, parsimonious, and novel conceptualization of the most important attributes of team effectiveness in cricket, with conceivable transferability to other team sports.


[Pheochromocytomas].
This study of pheochromocytoma addresses only the four aspects which changed dramatically. The diagnosis depends on the clinical picture, biological tests (plasma methoxamine) and the elimination of catecholamines and their metabolites. Abdominal CT scan localizes the tumor. M.I.B.G. scintigraphy is complementary. When the pheochromocytoma is part of a generalized endocrinopathy (MEN II) familial screening is essential. The incidence of malignant tumours is probably higher than the published 10%; these tumors are either of primary malignancy or malignant after a long latency period. Survival, even in primary malignant tumours is considerable. Multiple localizations are detected by M.I.B.G. scintigraphy and determine the treatment strategy. Surgical therapy with a near zero mortality is the factor which most favourably influenced the prognosis. The still high peroperative morbidity, not prevented by adrenolytic therapy, can be counteracted with appropriate pharmacological agents.


Mid-pregnancy fetal biometry, uterine artery Doppler indices and maternal demographic characteristics: role in prediction of small-for-gestational-age birth.
The aim of this study was to evaluate the role of mid-trimester fetal biometry, uterine artery Doppler indices and maternal demographics in prediction of small-for-gestational-age (SGA) birth. We conducted a retrospective cohort study in a single referral center. The study included 23 894 singleton pregnancies scanned between 19 and 24 weeks of gestation. Maternal demographics included age, body mass index and ethnicity. Fetal biometry, birthweight and uterine artery pulsatility index values were converted into centiles. Multivariable logistic regression analysis was performed and the predictive accuracy was assessed using receiver operating characteristic curve analysis. The main outcome measure was prediction of delivery of preterm and term SGA neonates defined as a birthweight in the lowest centile groups (<10th, <5th and <3rd centiles). Maternal ethnicity, fetal biometry and uterine artery Doppler indices were significantly associated with the risk of SGA <5th centile (p < 0.01). Maternal factors or fetal biometry alone showed poor to moderate performance in prediction of term and preterm SGA <5th centile at a 10% false-positive rate. Uterine artery pulsatility index alone was able to predict 25, 60 and 77% of SGA <5th centile delivering at >37, <37 and <32 weeks of gestation respectively at a 10% false-positive rate; maternal factors, fetal biometry and uterine artery Doppler combined detected 40, 66 and 89% of term, preterm and very preterm SGA <5th centile at a 10% false-positive rate. Second-trimester screening can identify the majority of pregnancies at high risk of SGA birth and showed a higher performance for earlier gestational ages at birth and lower birthweight centiles.


Understanding dental plaque; biofilm dynamics.
A biofilm is a well organized community of cooperating microorganisms. Biofilms predictably form in nature, in artificial environments, and on medically implanted prostheses and indwelling venous catheters. They also form on tooth surfaces in the form of dental plaque. The intent of this article is to aid in the understanding of dental plaque by exploring biofilm structure, nature and dynamics. Understanding plaque facilitates its treatment and control.


[Rene Leriche, pioneer of modern surgery].
René Leriche (1879-1955) is not unknowned, but he has an important place in surgery. He is one of the glory of the contemporary surgery. He has dominated the French surgery during more than thirty years. The life of Leriche is specified: Lyon, medical career, marriage, military service, first world war, Strasbourg, Collage de France, second world war, Académie des Sciences; he was president of the Académie de Chirurgie, chief of the surgical department of the American Hospital; retirement, and death. His scientific work is eminent: surgery of pain, of the sympathic system, vascular surgery, experimental surgery, medical teaching in France, and the Ordre des Mêdecins. Leriche was a fervent patriot and served France to the best of his ability in peace, in war and during occupation by the enemy.


The search for an alternative to piped water and sewer systems in the Alaskan Arctic.
Forty-two communities in rural Alaska are considered unserved or underserved with water and sewer infrastructure. Many challenges exist to provide centralized piped water and sewer infrastructure to the homes, and they are exacerbated by decreasing capital funding. Unserved communities in rural Alaska experience higher rates of disease, supporting the recommendation that sanitation infrastructure should be provided. Organizations are pursuing alternative solutions to conventional piped water and sewer in order to maximize water use and reuse for public health. This paper reviews initiatives led by the State of Alaska, the Alaska Native Tribal Health Consortium, and the Yukon Kuskokwim Health Corporation to identify and develop potential long-term solutions appropriate and acceptable to rural communities. Future developments will likely evolve based on the lessons learned from the initiatives. Recommendations include Alaska-specific research needs, increased end-user participation in the design process, and integrated monitoring, evaluation, and information dissemination in future efforts.


5-Cyclo-pentyl-3-methyl-sulfinyl-2-phenyl-1-benzofuran.
In the title compound, C(20)H(20)O(2)S, the cyclo-pentyl ring adopts an envelope conformation with the flap atom connected to the benzofuran residue. The phenyl ring makes a dihedral angle of 32.36 (9)° with the mean plane of the benzofuran fragment. In the crystal, mol-ecules are linked through weak C-H⋯O inter-actions. In the cyclo-pentyl ring, two adjacent C atoms are disordered over two sets of sites with site occupancy factors of 0.675 (8) and 0.325 (8).


Efficient protocols for in vitro regeneration of Pennisetum glaucum (L) Br.
A system was developed for in vitro regeneration of Pennisetum glaucum through organogenesis and somatic embryogenesis. Mature embryo and leaf base explants of Pennisetum glaucum (L) Br. cv HH B60 (Poaceae) were cultured on Murashige and Skoog agar medium supplemented with 11.3 microM of 2,4-D for callus induction. Embryogenic calli were induced within eight weeks. Percentage of callus induction and somatic embryogenesis was significantly higher in mature embryo than leaf base explants. Maximum shoot regeneration was obtained via organogenesis on MS medium supplemented with 4.43 microM of BAP and 4.64 microM of kinetin from the calli of both the explants. The frequency of plant regeneration through somatic embryogenesis was comparatively lower than organogenesis. Regeneration frequency was higher in mature embryo explants than leaf base explants. The shoots regenerated via organogenesis were elongated and rooted efficiently on MS medium supplemented with IBA (0.49 microM). The rooted plantlets were hardened and transferred to soil.


A beta-turn rich barley seed protein is correctly folded in Escherichia coli.
Wild-type and cysteine-containing mutant C hordeins from barley were expressed in Escherichia coli at high levels (> or = 30mg/liter). N-terminal sequence analysis, SDS-PAGE, RP-HPLC, cd spectroscopy, and small angle X-ray scattering demonstrated that their physicochemical properties were similar to those of C hordeins isolated from barley grain. This indicates that the expressed proteins were correctly folded. The cysteine-containing mutant showed evidence of polymer formation in E. coli, nonreduced preparations of the protein showing the presence of polymers that were replaced by a single protein when a reducing agent was added.


LncRNA RCAT1 promotes tumor progression and metastasis via miR-214-5p/E2F2 axis in renal cell carcinoma.
Renal cell carcinoma is the second malignant tumors in the urinary system with high mortality and morbidity. Increasing evidence suggests that long non-coding RNAs (lncRNAs) play critical roles in tumor development and progression. In the current study, based on the publicly available data obtained from GEO and TCGA database, we identified five prognosis-related lncRNAs with the ability to predict the prognosis of patients with renal cell carcinoma. Among them, the uncharacterized and upregulated lncRNA RCAT1 (renal cancer-associated transcript 1) was identified as the key lncRNA. Our data further revealed that the expression of lncRNA RCAT1 was significantly upregulated in renal cell carcinoma tissues and cells. Gain-of-function and loss-of-function studies showed that lncRNA RCAT1 promoted cell proliferation, migration, and invasion in vitro and in vivo. Furthermore, we verified that lncRNA RCAT1 could abundantly sponge miR-214-5p, which served as a tumor suppressor in renal cell carcinoma. Significantly, miR-214-5p overexpression could attenuate the promotion of cell proliferation and metastasis induced by lncRNA RCAT1. Moreover, we found that E2F2 was a direct target of miR-214-5p, and lncRNA RCAT1 could protect E2F2 from miR-214-5p-mediated degradation. Taken together, our findings suggested that lncRNA RCAT1 could enhance the malignant phenotype of renal cell carcinoma cells by modulating miR-214-5p/E2F2 axis, and lncRNA RCAT1 might be a novel prognostic biomarker and a potential therapeutic target for renal cell carcinoma.


The enlarged carotid body of the chronically hypoxic and chronically hypoxic and hypercapnic rat: a morphometric analysis.
Rats were subjected to chronic hypoxia (10% O2) or hypoxia and hypercapnia (10% O2 + 4% CO2) for 3-4 weeks and their carotid bodies (twenty-three from twenty rats) were compared with those of litter-mate controls. Both chronic exposures, which simulated high altitude or chronic lung disease, caused a 4-10-fold increase in carotid body volume. The larger increases were attributed to higher fixation-perfusion pressures. The organs were fixed by perfusion with glutaraldehyde. Semi-thin (1 micron) sections for light microscopy and ultra-thin sections for electron microscopy were cut at regular intervals and were examined by stereological techniques to determine the nature of the enlargement. The proportion occupied by blood vessels was much increased in both chronic hypoxia and hypoxia plus hypercapnia; the endothelium appeared stretched with conspicuous fenestrations. There were increased numbers of endothelial cells which suggested new growth as well as stretching of endothelium and the mean transectional area of the vessels was increased. The mean surface area of blood vessels per unit area of carotid body was unaltered but the total surface area of blood vessels in the whole carotid body was greatly increased. Both the Type 1 cell nucleus and cytoplasm were increased in size. The proportion nucleus/cytoplasm was unaltered in hypoxia but reduced in hypoxia plus hypercapnia. There were fewer Type 1 cell nuclei per unit area but the estimated total number of Type 1 cell nuclei per carotid body was increased 2-4-fold; this was interpreted as Type 1 cell hyperplasia. Some of the dense-cored vesicles in Type 1 cells were enlarged with eccentric dense cores but their number per unit area of cytoplasm was decreased. Their mean size was not significantly altered. However, the total number of vesicles per carotid body was presumed to be increased because their decreased density in the cell was offset by a greater increase in total Type 1 cell volume. The harmonic and arithmetic mean distances between endothelium and the boundary of glomus tissue were significantly reduced. The harmonic mean distance is an indication of the diffusion distance for gases to and from blood and glomus tissue. The arithmetic mean distance is a measure of the amount of tissue in between. The significance of the vascular enlargement and hyperplasia and the Type 1 cell hyperplasia cannot be assessed at present. We do not know if enlargement is associated with the same, greater, or lesser activity of the organ for a given stimulus.


Isolation of human alpha-1 fetoprotein (AFP) from induced abortion material.
The isolation of alpha-1 fetoprotein (AFP) from material of an induced abortion is described. AFP is purified by anion exchange chromatography on DEAE-Sephadex A 50, affinity chromatography on Con-A-Sepharose, and preparative electrophoresis on agarose gel. The yield is about 10% of the original material. The purity was demonstrated by agarose gel electrophoresis and two-dimensional immunoelectrophoresis. The high concentration of AFP in material of induced abortion makes it particularly suitable for deriving human AFP.


End-tidal carbon dioxide concentration can estimate the appropriate timing for weaning off from extracorporeal membrane oxygenation for refractory circulatory failure.
Although extracorporeal membrane oxygenation (ECMO) is widely used as temporary circulation support, there are no reports of direct parameters indicating cardiac recovery to determine the timing of weaning off. Twenty-five patients supported by ECMO due to hemodynamic deterioration were divided into 2 groups according to their outcome: weaned ECMO (W: n = 18) or not (NW: n = 7). In the W group, we examined the differences in parameters between the 2 time points, ECMO introduction, and the reduction in ECMO flow to 40% of the initial setting known as the conventional recovery point (C-point). Significant differences were observed in systolic pulmonary artery pressure, the cardiac index measured by the thermodilution method, C-reactive protein, lactate, base excess, and the end-tidal CO(2) concentration (ETCO(2)). Next, by closely examining these 6 parameters measured every 12 hours, we found that only ETCO(2) had always changed steeply, like a 'flexion point' (E-point), in all W cases, but not in NW. The E-point was defined as an initial increase in ETCO(2) of >or= 5 mmHg over the preceding 12 hours with a continued rise over the next 12 hours. E-points appeared as much as 95 +/- 60 hours earlier than C-points and also preceded weaning off of ECMO. ETCO(2) can be a useful continuous parameter for predicting the adequate timing of weaning off of ECMO for circulatory failure at the bedside.


Participatory evaluation of counselling, medical and social services of The AIDS Support Organization (TASO) in Uganda.
The AIDS Support Organization (TASO) is an indigenous non-governmental organization (NGO) of HIV-infected and affected people in Uganda. TASO provides counselling, social support, medical and nursing care for opportunistic infections at 7 centres affiliated to district hospitals in Uganda. Between 1993 and 1994, the services provided by TASO were evaluated through a participatory approach between staff and clients. TASO counselling services helped clients and their families to cope with HIV and AIDS, with 90.4% of clients revealing their serostatus, and 57.2% reporting consistent use of condoms in the past 3 months. TASO was also the main source of medical care for clients with opportunistic infections in the last 6 months (63.8%). As a result of counselling, over half of the clients (56.9%) made plans for the future and 51.3% wished to make wills. There was a high level of acceptance of people living with HIV/AIDS (PWAs) by families (79%) and the community (76%). Care was provided to PWAs at home mainly by women (86.2%). TASO has demonstrated that individuals and their families are able to live positively with HIV/AIDS. Through counselling, medical care and material support to clients and their families, TASO has effected change in people's attitudes, knowledge and lifestyles. In particular, TASO has demonstrated a strong capacity to overcome four problems that haunt AIDS care in most places: (1) revealing one's HIV-serostatus to relevant others; (2) accepting PWAs in family and community; (3) seeking early treatment; and (4) combining prevention and care. In general, TASO has shown that specialized services to meet AIDS care needs can be added to existing health services at district levels. As a result of the participatory evaluation, a well-accepted monitoring system was established.


The DNA repair proteins BRCA1 and ERCC1 as predictive markers in sporadic ovarian cancer.
This study compares Breast Cancer 1 (BRCA1) and excision repair cross complementation group 1 (ERCC1) expression as predictive markers and evaluates the in vitro enhancement of platinum sensitivity using targeted agents in sporadic ovarian cancer (OC). A retrospective study was performed of advanced stage OC patients receiving platinum-based chemotherapy. BRCA1 and ERCC1 mRNA expression was determined from frozen tissue of 51 patients. Median overall survival (OS) was longer for patients with lower BRCA1 vs. higher BRCA1 (46 vs.33 months, p = 0.03). High BRCA1 was predictive of poorer OS specifically in patients with residual disease (RD) <2 cm (p = 0.03). There was a non-significant association for patients with lower ERCC1 and RD <2 cm in favor of improved OS and time to progression. Patients who expressed higher levels of both BRCA1 and ERCC1 mRNA had a shorter OS compared to patients with lower levels of either or both transcript (33 vs.46 months, p = 0.04). When Cox proportional modeling was used by representing BRCA1 and ERCC1 mRNA expression as a continuous variable, both emerge as potential predictors of survival. OC cell lines were exposed to chemotherapy in combination with DNA repair pathway inhibitors and cell viability was assessed. In vitro histone deacetylase (HDAC) inhibition increased the sensitivity of A2780s/cp cells to cisplatin and carboplatin but not to taxol, coincident with a significant decrease in BRCA1 and ERCC1 expression, suggesting that this compound directly targets DNA repair. In summary, this study shows that low BRCA1 and ERCC1 expression correlate with improved survival in advanced OC and HDAC inhibition induces synergistic cytotoxicity with platinum in vitro.


How Smart Technology Affects the Well-Being and Supportive Learning Performance of Logistics Employees?
The rapid improvement of technologies such as artificial intelligence in recent years has resulted in the development of smart technologies (ST) that can influence learning performance in different fields. The purpose of study is to explore the link between smart technology and learning performance. Using the S-O-R model as a framework, the researchers argue that smart technology (Stimuli) will increase corporate trust, self-efficacy, and well-being (Organism), resulting in improved learning performance (Response). The current model regards corporate trust and self-efficacy as relationship factors and investigates their direct influence on employee well-being and learning performance and the mediating role played by these variables. Additionally, the function of employee well-being in moderating the relationship between corporate trust, self-efficacy, and employee learning performance is also explored. The respondents (n = 516) in the present study are made up of employees from 10 logistics companies located in China. The data analysis is conducted using the AMOS software. The results show that that smart technologies can affect learning performance through corporate trust, self-efficacy, and employee well-being. The implementation of smart technology initiatives by corporations may provide positive workplace outcomes for employees (increased well-being), corporations (more engagement in workplace learning performance), and the relationship between employees and the companies that employ them (corporate trust and self-efficacy).


Understanding COPD-overlap syndromes.
Chronic obstructive pulmonary disease accounts for a large burden of lung disease. It can 'overlap' with other respiratory diseases including bronchiectasis, fibrosis and obstructive sleep apnea (OSA). While COPD alone confers morbidity and mortality, common features with contrasting clinical outcomes can occur in COPD 'overlap syndromes'. Areas covered: Given the large degree of heterogeneity in COPD, individual variation to treatment is adopted based on its observed phenotype, which in turn overlaps with features of other respiratory disease states such as asthma. This is coined asthma-COPD overlap syndrome ('ACOS'). Other examples of such overlapping clinical states include bronchiectasis-COPD ('BCOS'), fibrosis-COPD ('FCOS') and OSA-COPD ('OCOS'). The objective of this review is to highlight similarities and differences between the COPD-overlap syndromes in terms of risk factors, pathophysiology, diagnosis and potential treatment differences. Expert commentary: As a consequence of COPD overlap syndromes, a transition from the traditional 'one size fits all' treatment approach is necessary. Greater treatment stratification according to clinical phenotype using a precision medicine approach is now required. In this light, it is important to recognize and differentiate COPD overlap syndromes as distinct disease states compared to individual diseases such as asthma, COPD, fibrosis or bronchiectasis.


scDoc: correcting drop-out events in single-cell RNA-seq data.
Single-cell RNA-sequencing (scRNA-seq) has become an important tool to unravel cellular heterogeneity, discover new cell (sub)types, and understand cell development at single-cell resolution. However, one major challenge to scRNA-seq research is the presence of 'drop-out' events, which usually is due to extremely low mRNA input or the stochastic nature of gene expression. In this article, we present a novel single-cell RNA-seq drop-out correction (scDoc) method, imputing drop-out events by borrowing information for the same gene from highly similar cells. scDoc is the first method that directly involves drop-out information to accounting for cell-to-cell similarity estimation, which is crucial in scRNA-seq drop-out imputation but has not been appropriately examined. We evaluated the performance of scDoc using both simulated data and real scRNA-seq studies. Results show that scDoc outperforms the existing imputation methods in reference to data visualization, cell subpopulation identification and differential expression detection in scRNA-seq data. R code is available at https://github.com/anlingUA/scDoc. Supplementary data are available at Bioinformatics online.


[Number needed to be screened in a study: a novel measure for disease screening effect].
To introduce the concept, methods for calculation and application of "number needed to be screened" (NNBS) in epidemiologic studies. The concept of "number needed to treat" (NNT) was extended for disease screening strategies. For the purpose of illustration, the values of number needed to invite for screening (NNI) and number needed to be screened (NNBS) were calculated on the basis of the results from two randomized controlled screening trials--Nottingham randomized controlled trial of faecal-occult-blood screening for colorectal cancer and Swedish mammographic screening trial for breast cancer in two counties. In order to prevent one death from the colorectal cancer among local people aged from 45 to 74 during the 14 years of follow-up, the NNI and NNBS for faecal-occult-blood screening program were 1220 and 665, respectively. In addition, in order to prevent one death from breast cancer among local women aged 40-74 during 8 years of follow-up, the NNI and NNBS for mammographic screening program were 1961 and 1494, respectively. Compared with the traditional indices, NNBS can evaluate the overall effectiveness of a screening program in an intuitively understandable manner so as to facilitate the communication among medical researchers, health workers, health policy makers and the public.


Wood creosote prevents CRF-induced motility via 5-HT3 receptors in proximal and 5-HT4 receptors in distal colon in rats.
Wood creosote has been used as an herbal medicine against acute diarrhea caused by food poisoning and has an inhibitory effect on colonic motility and enterotoxin-induced ion secretion. Since no previous studies have examined the effects of wood creosote on stress-induced alteration of colonic motility, we examined the effects on the colonic motility altered by intracerebroventricular (i.c.v.) injection of corticotropin-releasing factor (CRF), which is a key mediator in responses to stress. We recorded motor activity in proximal and distal colon of unrestrained conscious rats via two manometory catheters. The frequencies of phase III-like contraction and the % motor indices in both proximal and distal colon were measured. At the same time the number of fecal pellets excreted was counted. I.c.v. injection of CRF increased the motor activity in both proximal and distal colon, and these effects were completely antagonized by i.c.v. injection of a selective CRF type 1 antagonist but not by a CRF type 2 antagonist. Changes in colonic motility induced by CRF were reversed by intravenously administered wood creosote. Intraluminal administration of the 5-HT(3) receptor antagonist granisetron, or the 5-HT(4) receptor antagonist SB 204070 blocked the increase in colonic motility induced by i.c.v. injection of CRF. Wood creosote prevented the increase in colonic motility induced by the 5-HT(3) receptor agonist SR57227A in the proximal colon, while it prevented the increase in colonic motility induced by the 5-HT(4) receptor agonist RS67506 in the distal colon. These results indicate that wood creosote prevents the increase in colonic motility induced by CRF via 5-HT(3) receptors in the proximal colon, and via 5-HT(4) receptors in the distal colon, suggesting that wood creosote might be useful to treat stress-induced diarrhea.


Fabrication of Spherical and Worm-shaped Micellar Nanocrystals by Combining Electrospray, Self-assembly, and Solvent-based Structure Control.
Micellar nanocrystals (micelles with encapsulated nanocrystals) have become an emerging major class of nanobiomaterials. We describe a method of fabricating micellar nanocrystals based on combining top-down electrospray, bottom-up self-assembly, and solvent-based structure control. This method involves first using electrospray to generate uniform ultrafine liquid droplets, each of which functions as a micro-reactor in which self-assembly reaction occurs forming micellar nanocrystals, with the structures (micelle shape and nanocrystal encapsulation) controlled by the organic solvent used. This method is largely continuous and produces high quality micellar nanocrystal products with an inexpensive structure control approach. By using a water-miscible organic solvent tetrahydrofuran (THF), worm-shaped micellar nanocrystals can be produced due to solvent-induced/facilitated micelle fusion. Compared with the common spherical micellar nanocrystals, worm-shaped micellar nanocrystals can offer minimized non-specific cellular uptake, thus enhancing biological targeting. By co-encapsulating multiple nanocrystals into each micelle, multifunctional or synergistic effects can be achieved. Current limitations of this fabrication method, which will be part of the future work, primarily include imperfect encapsulation in the micellar nanocrystal product and the incompletely continuous nature of the process.


Optimal interpretative strategy for preoperative parathyroid scintigraphy.
Our objective was to retrospectively compare various scintigraphic methods to determine their relative accuracies and interobserver variabilities in preoperative localization of single-gland disease in patients with primary hyperparathyroidism. We studied 292 patients who underwent preoperative parathyroid scintigraphy and surgical resection between June 2002 and September 2008. Imaging included early and delayed pinhole Tc-MIBI imaging (including anterior oblique images), similar I imaging, and MIBI SPECT. Seven different imaging combinations were assessed as follows: early MIBI only, delayed MIBI only, comparison of dual-phase early and delayed MIBI, visual subtraction of early MIBI and I images, all planar images, SPECT only, and all planar and SPECT images (ALL). Each data set was reviewed by 2 of 4 experienced nuclear physicians without knowledge of clinical information or final diagnosis. Imaging results were compared with surgical outcomes. The accuracy of ALL imaging for delineating abnormal/normal parathyroid glands by quadrant was 96%, 93%, 95%, and 95% for the 4 readers. The accuracies of visual subtraction of early MIBI and I images and all planar images were not significantly different from ALL for all 4 readers. All planar and SPECT images were significantly more accurate than early MIBI only, delayed MIBI only, or SPECT only for all 4 readers and better than comparison of dual-phase early and delayed MIBI for 3 of 4 readers. A rigorous combination of multiple imaging approaches yielded high accuracies across multiple readers for localization of a single offending parathyroid gland, but a more limited technique using MIBI/I subtraction imaging with anterior and anterior oblique pinhole images provided similarly high accuracy and limited interobserver variation of accuracy.


Adolescent pediatric pain tool for multidimensional measurement of pain in children and adolescents.
Very few multidimensional tools are available for measurement of pain in children and adolescents. We critically reviewed the scientific literature to examine the psychometrics and utility of the Adolescent Pediatric Pain Tool (APPT), a multidimensional self-report tool that evaluates the intensity, location, and quality (including affective, evaluative, sensory, and temporal) dimensions of pain. The APPT is available in English and Spanish for children and adolescents, and was modeled after the McGill Pain Questionnaire in adults. We found good evidence for construct validity, reliability, and sensitivity of the APPT for the measurement of pediatric pain. The APPT was used to measure pain in children with different conditions, such as cancer, sickle cell disease, orthopedic, traumatic injuries, and allergy testing. Although the APPT was designed to assess the multiple dimensions of pain, the majority of the reports included results only for the intensity ratings. Unlike the numerical and pediatric faces rating scales, which are widely used in clinical practice and research, the APPT is not limited to the single dimension of pain intensity. It measures multiple dimensions, and may be able to discriminate between nociceptive and neuropathic pain. The APPT is one of a few multidimensional pain measures that can help to advance the science of pediatric pain and its management. When the APPT is used in practice or research, the multiple dimensions of pain may be characterized and compared in different painful conditions. It may guide the use of multimodal interventions in children and adolescents with a variety of pain conditions.


The relationship between power and time to fatigue in cycle ergometer exercise.
The purpose of this study was to evaluate three critical power (P (critical)) models. Ten university students performed tests that elicited fatigue in > 2 min to approximately 10 min. Power and time data were fit to a 2-parameter hyperbolic model, a 3-parameter hyperbolic model, and a 3-parameter exponential model. Models described the power-time relationship well (R (2) > or = 0.995). However, P (critical) (209 +/- 51 W; SEE: 20 +/- 47 W) and the time constant (198 +/- 87 s; SEE: 103 +/- 246 W) from the exponential model have no obvious meaning. The 2-parameter model produced P (critical) (187 +/- 38 W) and anaerobic work capacity (20.4 +/- 9.0 kJ) that have known physiological meaning, with excellent confidence (SEE: 2 +/- 2 W and 1.0 +/- 1.0 kJ, respectively). Addition of a maximal power parameter to the 2-parameter model did not improve description of the relationship, and the third parameter was superfluous. The 2-parameter model was preferred because, for the range of exercise durations used in this study, it describes the power-relationship adequately and in a most parsimonious fashion.


Cathepsin D immobilized capillary reactors for on-flow screening assays.
The treatment of diseases using enzymes as targets has called for the development of new and reliable methods for screening. The protease cathepsin D is one such target involved in several diseases such as tumors, degenerative processes, and vital processes of parasites causing schistosomiasis. Herein, we describe the preparation of a fused silica capillary, cathepsin D (CatD)-immobilized enzyme reactor (IMER) using in a multidimensional High Performance Liquid Chromatography-based method (2D-HPLC) and zonal affinity chromatography as an alternative in the search for new ligands. The activity and kinetic parameters of CatD-IMER were evaluated by monitoring the product MOCAc-Gly-Lys-Pro-Ile-Leu-Phe (P-MOCAc) (KM = 81.9 ± 7.49 μmol/L) generated by cleavage of the fluorogenic substrate MOCAc-Gly-Lys-Pro-Ile-Leu-Phe-Phe-Arg-Leu-Lys(DNP)-d-Arg-NH2 (S-MOCAc). Stability studies have indicated that CatD-IMER retained 20% of activity after 5 months, a relevant result, because proteases are susceptible to autoproteolysis in solution assays with free enzyme. In the search for inhibitors, 12 crude natural product extracts were analyzed using CatD-IMER as the target, resulting in the isolation of different classes of natural products. In addition, 26 compounds obtained from different species of plants were also screened, demonstrating the efficiency and reproducibility of the herein reported assay even in the case of complex matrices such as plant crude extracts.


Enzymology below 200 K: the kinetics and thermodynamics of the photochemistry catalyzed by protochlorophyllide oxidoreductase.
The chlorophyll biosynthesis enzyme protochlorophyllide reductase (POR) catalyzes the light-dependent reduction of protochlorophyllide (Pchlide) into chlorophyllide in the presence of NADPH. As POR is light-dependent, catalysis can be initiated by illumination of the enzyme-substrate complex at low temperatures, making it an attractive model for studying aspects of biological proton and hydride transfers. The early stages in the photoreduction, involving Pchlide binding and an initial photochemical reaction, have been studied in vitro by using low-temperature fluorescence and absorbance measurements. Formation of the ternary POR-NADPH-Pchlide complex produces red shifts in the fluorescence and absorbance maxima of Pchlide, allowing the dissociation constant for Pchlide binding to be measured. We demonstrate that the product of an initial photochemical reaction, which can occur below 200 K, is a nonfluorescent intermediate with a broad absorbance band at 696 nm (A696) that is suggested to represent an ion radical complex. The temperature dependence of the rate of A696 formation has allowed the activation energy for the photochemical step to be calculated and has shown that POR catalysis can proceed at much lower temperatures than previously thought. Calculations of differences in free energy between various reaction intermediates have been calculated; these, together with the quantum efficiency for Pchlide conversion, suggest a quantitative model for the thermodynamics of the light-driven step of Pchlide reduction.


Ballistic Penetration of Highly Charged Nanoaerosol Particles through a Lipid Monolayer.
To be used as a drug, inhaled nanoaerosol particles (NAPs) must first penetrate the lipid layer on top of the lung fluid before they will be able to reach the lung epithelium. We investigated how the penetration of NAPs through a model lipid monolayer (LM) depends upon their charging level and size. It was shown that deposition of NAPs 20-200 nm in diameter and charged to the Rayleigh limit gradually increased the surface tension of a dipalmitoylphosphatidylcholine monolayer (DPPC), indicating a loss of lipid molecules from the monolayer. This phenomenon was reproduced with a variety of NAPs produced from glucose, proteins, and polymers. Transfer of the lipid material into the subphase was documented by direct visualization of lipid nanoparticles in the subphase with atomic force microscopy after deposition of glucose NAPs on a DPPC monolayer, followed by collection of the lipid nanoparticles on a mica surface. Partial restoration of tension upon storage indicates that some of the lipid may return to the monolayer. Experiments with the deposition of highly charged calibrated polystyrene nanoparticles showed that the amount of lipid removed from the surface was roughly proportional to the overall surface area of the deposited NAPs. When the number of charges on the NAPs was reduced from their Rayleigh level of 103-104 units to 1-10 units, no notable changes in monolayer surface tension were observed even with prolonged deposition of such NAPs. It was therefore concluded that only highly charged NAPs of a certain size acquire sufficient speed from their attraction by mirror charges to enable ballistic penetration through a lipid monolayer.


The risk for major depression conferred by childhood maltreatment is multiplied by BDNF and SERT genetic vulnerability: a replication study.
There is limited evidence for a moderating role of both serotonin transporter (SERT) and brain-derived neurotrophic factor (BDNF) genes on the risk for major depression (MD) developing after childhood maltreatment. However, research on this topic remains inconclusive, and there is a lack of data from longitudinal studies with large and representative population samples. Our study aimed to clarify whether, in the presence of previous childhood maltreatment, individuals carrying low functional alleles for both SERT 5-HTTLPR and BDNF Val66Met polymorphisms had a higher risk for MD. We explored 2- and 3-way gene (SERT and BDNF) × environment (childhood maltreatment) interactions in a large sample of Spanish adults who were followed up over a 3-year period and assessed in person for both DSM-IV MD and exposure to childhood maltreatment. Our study included 2679 participants. Those with both the 5-HTTLPR s allele and the BDNF Met allele showed the highest risk of MD if they had previously experienced emotional (z = 2.08, p = 0.037), sexual (z = 2.19, p = 0.029) or any kind of childhood abuse (z = 2.37, p = 0.018). These 3-way interactions remained significant regardless of whether the 5-HTTLPR triallelic or the 5-HTTLPR biallelic polymorphisms were included in the analyses. Retrospective assessment of childhood maltreatment may have resulted in a moderate degree of recall bias. Our results confirm that the risk of depression conferred by childhood maltreatment is modified by variation at both SERT and BDNF genes.


Who Will Be Culpable?
A registered nurse of questionable professional competence, with a dodgy employment record, a history of mental illness and substance abuse, remains employed and ultimately murders eight vulnerable seniors, attempts to murder four others, and assaults another two over the course of a decade. At least those are the ones for which Elizabeth Wettlaufer offered a confession. Like most nurses and citizens, I was horrified by the revelation of multiple homicides at the hand of one of us. How could such a confluence of incompetence, mental illness and addiction, and willful murder go undetected for so long by so many?


Sinus tachycardia: don't blame the whistle-blower.
Sinus tachycardia due to sympathetic activation may be the ultimate response to support cardiac output. Abrupt heart rate reduction in this condition may be deleterious as is illustrated by two cases. Both patients were referred in cardiogenic shock after inappropriate treatment with a beta-blocking agent, initiated as a symptomatic treatment of a sinus tachycardia.Thus even if beta-blocking agents provoked a paradigm shift in the understanding of heart failure and became a cornerstone of the treatment, therapy should be initiated with knowledge of the underlying condition.


[The "Spanish flu" pandemic of 1918-1919 in La Réunion (Indian Ocean)].
Brought in by the ship Madonna, which was taking local survivors of World War I back to Reunion, the 1918 Spanish flu pandemic reached the island in March 1919 and lasted for three months. The controversies between doctors and between doctors and the colonial administrators, officials' desertion of their posts, and food shortages together caused a major panic. The epidemic appears to have ravaged people under the age of 40 and the most disadvantaged neighborhoods, at a period when the economy was already in the doldrums and the population had been declining since the late 19th century. Estimates indicate 2000 deaths in the capital of Saint-Denis, among a population of 25,000 inhabitants, and 7 to 20,000 deaths on the island as a whole, representing 4-11% of the population - far more than the 949 local soldiers killed on the battlefields of Europe. According to legend, salvation came from the sky as a small cyclone on May 11, 1919: it lasted an hour, swept away the "miasmas" and washed the island clean of all its impurities.


Tobacco dependence in a UK Bangladeshi female population: a cross-sectional study.
The objective of this study was to establish the prevalence of paan chewing with tobacco by UK-resident Bangladeshi women and the extent to which they manifest nicotine dependence. The cross-sectional study was conducted at two local authority housing estates in Tower Hamlets, London. Participants were 242 Bangladeshi women, selected at random from the current electoral register, who supplied a saliva sample for cotinine and an expired air sample for carbon monoxide analysis. They also participated in a structured interview assessing knowledge, attitudes and behavior with respect to tobacco use. Main outcome measures were data on tobacco use and nicotine dependence, assessed by questionnaire and intake measures. The population prevalence of chewing paan quid with tobacco was 48.5% (95% confidence interval, CI 42.01-54.98%), while 4% (95% CI 2.05-7.41%) smoked cigarettes. Higher mean salivary cotinine scores were associated with greater consumption frequency and use of leaf tobacco in the quid. Above-average nicotine dependence was associated with chewing paan quid with tobacco within 1 h of waking (OR = 4.02, p = 0.03, 95% CI 1.08-14.94) and the use of leaf rather than processed tobacco (OR = 3.91, p = 0.025, 95% CI 1.19-12.81). Smoking prevalence is low, but the prevalence of paan quid with tobacco chewing is high in this sample of Bangladeshi women. Cotinine concentration appears to be a reliable indicator of levels of nicotine dependence among paan quid with tobacco chewers. Questionnaire-derived items can be used to identify those with above-average levels of nicotine dependence.


Directed fixed energy sandpile model.
We numerically study the directed version of the fixed energy sandpile. On a closed square lattice, the dynamical evolution of a fixed density of sand grains is studied. The activity of the system shows a continuous phase transition around a critical density. While the deterministic version has the set of nontrivial exponents, the stochastic model is characterized by mean field like exponents.


Prenatal development of the eye in the golden hamster.
Prenatal development of the eye in golden hamsters is described at the light microscopic level as twelve periods based on salient morphological features. Period one includes shallow and deepened optic sulci in the cephalic neural plate and closing prosencephalon. Period two shows V-shaped prosencephalic evaginations, and Period three, bulbous vesicles. Contact of the retinal disc and lens placode at Period four precedes presumptive retinal invagination and lens pit formation during Period five. During Period six an open lens vesicle, precociously expanded dorsal and lateral optic cup regions and widespread optic fissure margins are evident. A spherical lens lumen, deepened optic cup and narrow optic fissure characterize Period seven. At Period eight posterior lens fibers are elongated, the optic cup is expanded ventrally, and optic fissure margins are juxtaposed or fusing. By Period nine the lens lumen is nearly or completely occluded, the optic fissure is essentially fused and axonal fibers are exiting from the globe. During Period ten corneal components are associated, axonal processes extend to the diencephalon, and lid folds cover more than half of the cornea. By Period eleven eyelids are fused. Anteriorly the pigmented epithelium is thickened and densely pigmented; outer and inner neuroblastic retinal layers are clearly distinguishable. Period twelve is marked by conspicuous anterior folds of pigmented epithelium; a relatively anuclear zone virtually separates outer and inner neuroblastic layers of the retina.


Copy number variation and neuropsychiatric problems in females and males in the general population.
Neurodevelopmental problems (NPs) are more common in males, whereas anxiety and depression are more common in females. Rare copy number variants (CNVs) have been implicated in neurodevelopmental disorders. The aim of this study was to characterize the relationship between rare CNVs with NPs, anxiety, and depression in a childhood population sample, as well as to examine sex-specific effects. We analyzed a sample of N = 12,982 children, of whom 5.3% had narrowly defined NPs (clinically diagnosed), 20.9% had broadly defined NPs (based on validated screening measures, but no diagnosis), and 3.0% had clinically diagnosed anxiety or depression. Rare (<1% frequency) CNVs were categorized by size (100-500 kb or > 500 kb), type, and putative relevance to NPs. We tested for association of CNV categories with outcomes and examined sex-specific effects. Medium deletions (OR[CI] = 1.18[1.05-1.33], p = .0053) and large duplications (OR[CI] = 1.45[1.19-1.75], p = .00017) were associated with broadly defined NPs. Large deletions (OR[CI] = 1.85[1.14-3.01], p = .013) were associated with narrowly defined NPs. There were no significant sex differences in CNV burden in individuals with NPs. Although CNVs were not associated with anxiety/depression in the whole sample, in individuals diagnosed with these disorders, females were more likely to have large CNVs (OR[CI] = 3.75[1.45-9.68], p = .0064). Rare CNVs are associated with both narrowly and broadly defined NPs in a general population sample of children. Our results also suggest that large, rare CNVs may show sex-specific phenotypic effects.


Ionic channel function in action potential generation: current perspective.
Over 50 years ago, Hodgkin and Huxley laid down the foundations of our current understanding of ionic channels. An impressive progress has been made during the following years that culminated in the revelation of the details of potassium channel structure. Nevertheless, even today, we cannot separate well currents recorded in central mammalian neurons. Many modern concepts about the function of sodium and potassium currents are based on experiments performed in nonmammalian cells. The recent recognition of the fast delayed rectifier current indicates that we need to reevaluate the biophysical role of sodium and potassium currents. This review will consider high quality voltage clamp data obtained from the soma of central mammalian neurons in the view of our current knowledge about proteins forming ionic channels. Fast sodium currents and three types of outward potassium currents, the delayed rectifier, the subthreshold A-type, and the D-type potassium currents, are discussed here. An updated current classification with biophysical role of each current subtype is provided. This review shows that details of kinetics of both sodium and outward potassium currents differ significantly from the classical descriptions and these differences may be of functional significance.


Function of stiff joints may be restored by Ilizarov joint distraction.
Three patients with joint stiffness caused by trauma or infection are reported. The involved joints are the interphalangeal joint of the thumb, patellofemoral joint, and ankle joint. As an alternative for the indicated arthrodesis in these patients, treatment with articulating joint distraction was performed. By use of adapted Ilizarov external ring fixators, gradual distraction was applied to loosen the joint, followed after loosening by a period of exercise during distraction. In all three patients this experimental approach led to a decrease in pain and improvement of joint function that persisted for at least 2 years after treatment. With the use of Ilizarov joint distraction, joint function in cases of joint stiffness may be restored, and the need for an arthrodesis can be postponed.


Spatially varying fat-water excitation using short 2DRF pulses.
Conventional spatial-spectral radiofrequency pulses excite the water or the fat spins in a whole slice or slab. While such pulses prove useful in a number of applications, their applicability is severely limited in sequences with short pulse repetition time due to the relatively long duration of the pulses. In the present work, we demonstrate that, by manipulating the parameters of a two-dimensional spartially-selective (2DRF) pulse designed to excite a two-dimensional spatial profile, the chemical-shift sensitivity of the pulse can be exploited to obtain potentially useful spatially varying fat-water excitation patterns.


Tonic immobility and factors influencing its duration in rats.
The author developed a method for inducing tonic immobility (paroxysmal inhibition) in rats and mice. By means of a plexiglass plate and plexiglass box the rat is immobilised, rotated at 180 degrees and subjected to constant pressure corresponding to the weight of the plexiglass plate. This way it is possible to prolong substantially tonic immobility in rats without using foregoing time consuming and interfering, so called sensitizing procedures. The duration of TI can be influenced by pharmacologic and nonpharmacological interventions. A longer duration of TI appeared to be typical for rats tending to react in other situations with anxiety, motor inhibition and submission.


Evaluation of audiovisual teaching materials in family practice: a report of review activities, 1979-1980.
Although audiovisual teaching materials are commonly used in medical education at all levels, it remains difficult for educators and interested learners to become aware of what is available, of good quality, and relevant to specific learning needs. The Audiovisual Review Committee has functioned since 1974 as a subcommittee of the Education Committee of the Society of Teachers of Family Medicine. This paper lists the audiovisual materials that have been reviewed during the last two years, and briefly comments upon the review process that has been used over the last seven years.


Convective and diffusive gas mixing in human lungs: experiments and model analysis.
Equilibration of inspired with lung residual gas was studied by a single-breath technique for varying breath-holding time with He, Ar, and SF6 as test gases. The ratio of end-expired (FE') to mean lung concentration after expiration (FL) was always below unity, indicating imperfect mixing of gas in the lung. The ratio of FL/FE' for all gases increased with tB, for any tB the ratio was smallest for SF6 and greatest for He. Similarly, Bohr dead space (VD) at any given tB was greatest for SF6 and smallest for He, with VD decreasing toward an asymptotic value common for all gases as tB increased. The results were analyzed quantitatively on a serial three-compartment model of the lung. Model analysis suggests that both diffusion and convection are effective in equilibrating test gases in the lung during breath holding. Further, stratified inhomogeneities in the absence of convective gas mixing in the alveolar space would seriously limit alveolar respiratory gas exchange; with convection, however, stratification is likely to impose only moderate constraints on resting gas exchange.


Preduodenal position of the common bile duct associated with annular pancreas: case report and literature review.
A preduodenal position of the common bile duct (PDCBD) is a very rare embryological anomaly. Our patient, a 1-day-old boy, was diagnosed to have PDCBD, annular pancreas, duodenal stenosis, intestinal malrotation and a ventricular septal defect associated with 21 trisomy. Initially the fetal diagnosis was duodenal atresia. The diagnosis of duodenal stenosis was made on birth, and he underwent an emergency operation 24 hours later. The PDCBD was discovered during the duodenoduodenostomy procedure. While a transversal incision was being made for the ventral wall in the distended proximal duodenum, the common bile duct was accidentally cut. We found the common bile duct to run into the ventral side of the duodenal wall. Subsequently, the common bile duct was repaired with a stent using microscopic techniques. The case is being reported because of the rarity of this condition and also to stress the importance of accurately recognizing this anomaly when treating the concomitant diseases, particularly when surgical implications are involved.


Congenitally missing permanent mandibular incisors and their association with missing primary teeth in the southern Chinese (Hong Kong).
A radiographic survey of a random sample of 454 girls aged 5.9 +/- 0.5 yr and 521 boys aged 5.8 +/- 0.4 y was undertaken to establish data on the incidence of congenitally missing mandibular incisor teeth amongst the Southern Chinese and to compare these figures with those of a similar previous study of 12-yr-olds so to eliminate factors such a trauma or extractions which may have artificially inflated the 12-yr-old incidence data. The proportion of 5-yr-old girls and boys affected by hypodontia in the permanent mandibular incisor region was 0.086 and 0.046 respectively (a significant difference between sexes, P < 0.02), compared with 0.047 and 0.034 for the 12-yr-olds (a non-significant difference) so other factors must have contributed to the discrepancy between the two groups of children. A very strong correlation (P < 10(-25)) between missing primary and missing permanent mandibular incisors is present in this group, and this has implications for prognosis and treatment planning. A fundamental developmental defect is implied.


Myoglobin as marker in meat adulteration: a UPLC method for determining the presence of pork meat in raw beef burger.
The identification of meat animal species used in raw burgers is very important with respect to economic and religious considerations. Therefore, international supervisory bodies have implemented procedures to control the employed meat species. In this paper we propose myoglobin as a powerful molecular marker to evaluate the presence of non-declared meat addition in raw beef burgers by using ultra-performance liquid chromatography (UPLC) for the separation and identification of edible animal species (beef, chicken, horse, ostrich, pig and water buffalo). Meat samples were pre-treated with sodium nitrite to transform oxymyoglobin and deoxymyoglobin to the more stable metmyoglobin. The developed method was validated, preparing mixtures with different percentages of pork and beef minced meat. The obtained results show that using myoglobin as marker, 5% (25 mg/500 mg) of pork or beef meat can be detected in premixed minced meat samples.


Y-23 mediated genetic data analysis of endogamous Brahmin population of Rajasthan, India.
India's largest state Rajasthan is known for its variable population groups including castes, communities and tribes. In the present article, Y-STR polymorphisms of hundred unrelated healthy male volunteers from the Brahmin population of Rajasthan, India were investigated using the Powerplex® Y-23 PCR amplification kit. Total 94 distinct haplotypes were obtained out of them 93 were singletons. Haplotype Diversity (HD) and Discrimination Capacity (DC) for the population were 0.644 and 0.9894 respectively. The Intra-population relationship between the present population data and other reported Indian populations was examined through Multidimensional Scaling (MDS) Plot, which shows the Brahmin population of Rajasthan lies in a cluster with the Brahmin populations of Haryana and Maharashtra. Data generated with 23 Y-STR markers is submitted on Y chromosome haplotype reference database (YHRD) (yhrd.org) and it will robust the forensic database of the Rajasthan population of India.


Methicillin-resistant Staphylococcus aureus colonization and infection risks from companion animals: current perspectives.
Methicillin-resistant Staphylococcus aureus (MRSA) remains one of the most virulent human pathogens and has also recently been recognized as such in the veterinary settings. Companion animals, including dogs, cats, horses, small exotic animals, wildlife animals, and livestock, may constitute a reservoir for MRSA transmission to humans and vice versa. The evolution, emergence, and risk factors for MRSA transmission among colonized or infected animals are reviewed in the present paper, and infection control practices are discussed.


Influence of macromolecular precipitants on phase behavior of monoclonal antibodies.
For the successful application of protein crystallization as a downstream step, a profound knowledge of protein phase behavior in solutions is needed. Therefore, a systematic screening was conducted to analyze the influence of macromolecular precipitants in the form of polyethylene glycol (PEG). First, the influence of molecular weight and concentration of PEG at different pH-values were investigated and analyzed in three-dimensional (3-D) phase diagrams to find appropriate conditions in terms of a fast kinetic and crystal size for downstream processing. In comparison to the use of salts as precipitant, PEG was more suitable to obtain compact 3-D crystals over a broad range of conditions, whereby the molecular weight of PEG is, besides the pH-value, the most important parameter. Second, osmotic second virial coefficients as parameters for protein interactions are experimentally determined with static light scattering to gain a deep insight view in the phase behavior on a molecular basis. The PEG-protein solutions were analyzed as a pseudo-one-compartment system. As the precipitant is also a macromolecule, the new approach of analyzing cross-interactions between the protein and the macromolecule PEG in form of the osmotic second cross-virial coefficient (B23 ) was applied. Both parameters help to understand the protein phase behavior. However, a predictive description of protein phase behavior for systems consisting of monoclonal antibodies and PEG as precipitant is not possible, as kinetic phenomena and concentration dependencies were not taken into account.


Representations of Codeine Misuse on Instagram: Content Analysis.
Prescription opioid misuse has doubled over the past 10 years and is now a public health epidemic. Analysis of social media data may provide additional insights into opioid misuse to supplement the traditional approaches of data collection (eg, self-report on surveys). The aim of this study was to characterize representations of codeine misuse through analysis of public posts on Instagram to understand text phrases related to misuse. We identified hashtags and searchable text phrases associated with codeine misuse by analyzing 1156 sequential Instagram posts over the course of 2 weeks from May 2016 to July 2016. Content analysis of posts associated with these hashtags identified the most common themes arising in images, as well as culture around misuse, including how misuse is happening and being perpetuated through social media. A majority of images (50/100; 50.0%) depicted codeine in its commonly misused form, combined with soda (lean). Codeine misuse was commonly represented with the ingestion of alcohol, cannabis, and benzodiazepines. Some images highlighted the previously noted affinity between codeine misuse and hip-hop culture or mainstream popular culture images. The prevalence of codeine misuse images, glamorizing of ingestion with soda and alcohol, and their integration with mainstream, popular culture imagery holds the potential to normalize and increase codeine misuse and overdose. To reduce harm and prevent misuse, immediate public health efforts are needed to better understand the relationship between the potential normalization, ritualization, and commercialization of codeine misuse.


Upper and lower time limits in the decision to recommend marrow transplantation for patients with chronic myelogenous leukaemia.
Long-term survival of patients with chronic myelogenous leukaemia (CML) requires marrow transplantation from a histocompatible donor. The optimal timing of the transplant is difficult to determine because of the high peritransplant mortality of 20-35% and the existence of a group of patients who can have the disease controlled by drug treatment for prolonged periods. We have developed a mathematical model implemented with a computer program which calculates lower and upper time limits for the timing of marrow transplantation. The lower time limit for transplantation is derived from the loss of life expectancy with delay, and the upper time limit is calculated by comparing the transplant survival probability with the probability of surviving an additional year without a transplant. Thus, an objective basis is provided for bracketing the most appropriate time for transplantation. This analysis suggests that the decision to transplant can be postponed in some patients for periods longer than may generally be recommended.


Controlled synthesis of Bi2S3/ZnS microspheres by an in situ ion-exchange process with enhanced visible light photocatalytic activity.
A novel Bi2S3/ZnS heterostructure has been synthesized through an in situ cation-exchange method between ZnS and bismuth(III) chloride. The obtained samples were characterized by multiform techniques, such as X-ray diffraction, field emission scanning electron microscopy, high-resolution transmission microscopy, UV-visible diffuse-reflectance spectroscopy, and photoluminescence spectra. The photocatalytic activities of the obtained photocatalysts were measured by the degradation of rhodamine B (RhB) and refractory oxytetracycline (OTC) under visible-light irradiation (λ ≥ 400 nm). The as-prepared Bi2S3/ZnS photocatalysts exhibit wide absorption in the visible-light region and display superior visible-light-driven photocatalytic activities in degradation of RhB and OTC compared with pristine ZnS microspheres and Bi2S3 nanorods. The dramatic enhancement in the visible light photocatalytic performance of the Bi2S3/ZnS composites could be attributed to the effective electron-hole separations at the interfaces of the two semiconductors, which facilitate the transfer of the photoinduced carriers. The present study provides helpful insight into the design of novel and highly efficient sulfate heterostructure photocatalysts.


25 Years of PI5P.
The accidental discovery of PI5P (phosphatidylinositol-5-phosphate) was published 25 years ago, when PIP5K type II (phosphoinositide-4-phosphate 5-kinase) was shown to actually be a 4-kinase that uses PI5P as a substrate to generate PI(4,5)P2. Consequently, PIP5K type II was renamed to PI5P4K, or PIP4K for short, and PI5P became the last of the 7 signaling phosphoinositides to be discovered. Much of what we know about PI5P comes from genetic studies of PIP4K, as the pathways for PI5P synthesis, the downstream targets of PI5P and how PI5P affects cellular function all remain largely enigmatic. Nevertheless, PI5P and PI5P-dependent PI(4,5)P2 synthesis have been clearly implicated in metabolic homeostasis and in diseases such as cancer. Here, we review the past 25 years of PI5P research, with particular emphasis on the impact this small signaling lipid has on human health.


Neuroinflammation PET Imaging: Current Opinion and Future Directions.
Neuroinflammation is a key pathologic hallmark of numerous neurologic diseases, however, its exact role in vivo is yet to be fully understood. PET imaging enables investigation, quantification, and tracking of different neuroinflammation biomarkers in living subjects longitudinally. One such biomarker that has been imaged extensively using PET is translocator protein 18 kDa (TSPO). Although imaging TSPO has yielded valuable clinical data linking neuroinflammation to various neurodegenerative diseases, considerable limitations of TSPO PET have prompted identification of other more cell-specific and functionally relevant biomarkers. This review analyzes the clinical potential of available and emerging PET biomarkers of innate and adaptive immune responses, with mention of exciting future directions for the field.


The ether lipid precursor hexadecylglycerol stimulates the release and changes the composition of exosomes derived from PC-3 cells.
Exosomes are vesicles released by cells after fusion of multivesicular bodies with the plasma membrane. In this study, we have investigated whether ether lipids affect the release of exosomes in PC-3 cells. To increase the cellular levels of ether lipids, the ether lipid precursor hexadecylglycerol was added to cells. Lipidomic analysis showed that this compound was in fact able to double the cellular levels of ether lipids in these cells. Furthermore, increased levels of ether lipids were also found in exosomes released by cells containing high levels of these lipids. Interestingly, as measured by nanoparticle tracking analysis, cells containing high levels of ether lipids released more exosomes than control cells, and these exosomes were similar in size to control exosomes. Moreover, silver staining and Western blot analyses showed that the protein composition of exosomes released in the presence of hexadecylglycerol was changed; the levels of some proteins were increased, and the levels of others were reduced. In conclusion, this study clearly shows that an increase in cellular ether lipids is associated with changes in the release and composition of exosomes.


Antizyme Inhibitors in Polyamine Metabolism and Beyond: Physiopathological Implications.
The intracellular levels of polyamines, cationic molecules involved in a myriad of cellular functions ranging from cellular growth, differentiation and apoptosis, is precisely regulated by antizymes and antizyme inhibitors via the modulation of the polyamine biosynthetic and transport systems. Antizymes, which are mainly activated upon high polyamine levels, inhibit ornithine decarboxylase (ODC), the key enzyme of the polyamine biosynthetic route, and exert a negative control of polyamine intake. Antizyme inhibitors (AZINs), which are proteins highly homologous to ODC, selectively interact with antizymes, preventing their action on ODC and the polyamine transport system. In this review, we will update the recent advances on the structural, cellular and physiological functions of AZINs, with particular emphasis on the action of these proteins in the regulation of polyamine metabolism. In addition, we will describe emerging evidence that suggests that AZINs may also have polyamine-independent effects on cells. Finally, we will discuss how the dysregulation of AZIN activity has been implicated in certain human pathologies such as cancer, fibrosis or neurodegenerative diseases.


Mutations in the LKB1 tumour suppressor are frequently detected in tumours from Caucasian but not Asian lung cancer patients.
Somatic mutations of LKB1 tumour suppressor gene have been detected in human cancers including non-small cell lung cancer (NSCLC). The relationship between LKB1 mutations and clinicopathological characteristics and other common oncogene mutations in NSCLC is inadequately described. In this study we evaluated tumour specimens from 310 patients with NSCLC including those with adenocarcinoma, adenosquamous carcinoma, and squamous cell carcinoma histologies. Tumours were obtained from patients of US (n=143) and Korean (n=167) origin and screened for LKB1, KRAS, BRAF, and EGFR mutations using RT-PCR-based SURVEYOR-WAVE method followed by Sanger sequencing. We detected mutations in the LKB1 gene in 34 tumours (11%). LKB1 mutation frequency was higher in NSCLC tumours of US origin (17%) compared with 5% in NSCLCs of Korean origin (P=0.001). They tended to occur more commonly in adenocarcinomas (13%) than in squamous cell carcinomas (5%) (P=0.066). LKB1 mutations associated with smoking history (P=0.007) and KRAS mutations (P=0.042) were almost mutually exclusive with EGFR mutations (P=0.002). The outcome of stages I and II NSCLC patients treated with surgery alone did not significantly differ based on LKB1 mutation status. Our study provides clinical and molecular characteristics of NSCLC, which harbour LKB1 mutations.


Concomitants of social acceptance: exploratory research and implications for treatment.
A population of 98 fourth and fifth grade students responded to instruments that yielded data on social acceptance, liking for others, need for approval, and interpersonal relationship orientation. Results suggest that social acceptance is related to interpersonal relationship orientation, but unrelated to liking for others and need for approval. Implications for treatment are discussed.


Acidification and assembly of porphyrin at an interface: counterion matching, selectivity, and supramolecular chirality.
The interfacial diprotonation and assemblies of a free-base achiral porphyrin, 5,10,15,20-tetrakis(3,5-dimethoxyphenyl)-21H,23H-porphine, on various acidic subphases were investigated. It has been shown that the compound could be diprotonated in situ on an acidic subphase and can form assemblies. The interfacially organized supramolecular assemblies were transferred onto a solid substrate, and the assemblies showed supramolecular chirality. Interestingly, the supramolecular chirality of the assemblies of the diprotonated species showed a counterion-dependent behavior. For the assemblies fabricated from the aqueous HCl subphases, a strong Cotton effect (CE) could be observed, although the porphyrin itself is achiral. When an aqueous HBr solution was used as the subphase, the assemblies showed a weak CE, whereas no CE could be detected for the assemblies formulated from the HNO3 or HI subphase. Interestingly, when a mixture of HBr and NaCl, or HNO3 and NaCl, was employed as the subphase, the formed assemblies displayed chiral features similar to those fabricated on the HCl subphase, suggesting that the Cl(-) could be preferentially visualized in terms of supramolecular chirality, although the system itself is composed of achiral species. On the basis of the experimental facts and a theoretical calculation, an explanation with regard to the different sizes of the counterions and the distinct binding affinities of the counteranions to the diprotonated porphyrin species has been proposed. Our findings provide new insights into the assembly of the diprotonated porphyrins as well as the interfacially occurring symmetry breaking.


Immobilized Escherichia coli BL21 as a catalyst for the synthesis of adenine and hypoxanthine nucleosides.
Different supports, such as alginate, agar, agarose, and polyacrylamide, were used to immobilize Escherichia coli BL 21 by entrapment techniques. The transglycosylation reaction involved in the synthesis of adenosine from uridine and adenine was chosen as a model system to study the characteristics of these biocatalysts. Whole cells immobilized on agarose proved to be optimal and could be used up to 30 times without significant loss of activity. This biocatalyst was further employed to test its ability in the synthesis of other adenine and hypoxanthine nucleosides. Ribo-, 2'-deoxyribo-, and arabinonucleosides could be prepared in high yields starting from the corresponding pyrimidine nucleosides and purine bases. Similar product yields were obtained with both free and immobilized cells, though, in the latter case, a longer reaction time was necessary.


Study of immunomodulatory effects of arteether administrated intratumorally.
Recent studies have indicated the profound anti-tumor activity of artemisinin's compounds, among which; arteether is an oil-soluble derivative of artemisinin with an endoperoxide bridge that can induce apoptosis in tumor cells but not in the normal cells. An experiment was carried out on tumor-bearing Balb/c mice to estimate the effects of Arteether on tumor growth and antitumor immune responses. Briefly, 6mg/kg/day of Arteether and diluents were administered to two groups of mice. Tumor sizes were measured using digital verniercallipers. Mice were sacrificed and splenocytes were harvested for lymphocyte proliferation assay, the level of IL-4 and IFN-γ cytokines, and the percentage of splenic T regulatory cells were measured. According to the findings, there were no statistical differences between the groups with respect to the level of IFN-γ, IL-4 and proliferation assay; while our results showed that Arteether is effective in the reduction of tumor growth rate. In general, intra-tumoral injection of Arteether as an oil-soluble derivative of artemisinin brings to light some antitumor properties that may aid in development of more effective antitumor agents.


Intrathecal application of drugs for muscle hypertonia.
The literature regarding the intrathecal use of morphine, baclofen, and midazolam to treat spasticity is reviewed. Nine patients with significant spasticity due to different etiologies were treated. Morphine and midazolam decreased spasticity but did not change the patient's functional status. Baclofen improved patient status, but was associated with significant CNS depression in two cases.


Xanthogranulomatous pancreatitis combined with intraductal papillary mucinous carcinoma in situ.
Xanthogranulomatous lesion is a rare condition in which lipid-laden histiocytes are deposited at various locations in the body. Xanthogranulomatous pancreatitis (XGP) associated with an intraductal papillary mucinous tumor (IPMT) is extremely rare. In this study, we described a case of XGP associated with IPMT and include a review of the literature. A pancreatic cystic mass was detected in a 72-yr-old woman by abdominal computed tomography. Pylorus-preserving pancreaticoduodenectomy was performed and diagnosis of XGP combined with intraductal papillary mucinous carcinoma in situ was made. After 13 months of follow-up, the patient is in good health without any evidence of tumor recurrence. Although XGP associated with IPMT is rare, we suggest that such cases should be brought to the attention of clinical investigators, as it may produce clinical features that mimic pancreatic cancer.


New Insights into the Pathophysiology and Treatment of Fibromyalgia.
Fibromyalgia is characterized by chronic widespread pain and several additional symptoms such as fatigue, cognitive dysfunction, depressive episodes, and anxiety. The underlying pathophysiology of fibromyalgia is still poorly understood, and treatment is often unsatisfactory. Current research provides evidence for altered pain processing in chronic pain patients, and specifically in fibromyalgia patients, possibly based on altered functional connectivity and brain chemistry in brain regions within the pain processing system. Besides discussing evidence from studies applying brain imaging (specifically resting state fMRI (Functional magnetic resonance imaging)), the current review aims at providing an overview of pharmacological and non-pharmacological treatment options. We will also summarize the most important results from recently performed brain imaging studies providing new insights into the potential mechanisms of various therapeutic approaches.


Rates of disappearance from plasma of enzymes labeled by coupling with a radioactive lodo-ester.
Lactate dehydrogenase-5 and creatine kinase from rabbit muscle were labeled by coupling with N-hydroxysuccinimidyl 3-(4'-hydroxy-[3',5'-125I]diiodophenyl)propionate. After purification, the analytical recovery of catalytically-active labeled enzyme averaged 90% for lactate dehydrogenase, 81% for creatine kinase. The labeled enzymes were injected intravenously into rabbits and disappearance from plasma of catalytic activity and radioactivity was measured. The disappearance curves for lactate dehydrogenase-5 differed considerably from those observed with the enzyme labeled by direct iodination. The discrepancy was due to rapid hydrolysis in vivo of the labeled amide-enzyme linkage, because about 50% of the injected radioactivity appeared in the urine as 125I-labeled 3-(4'-hydroxy-3',5'-diiodophenyl)propionic acid within 4-8 h of injection. Similar outputs were observed after administration of this acid to rabbits. The free acid was also detected in the urines of rabbits within 4-8 h of the intravenous injection of creatine kinase labeled similarly. We conclude that this method of labeling is unsuitable for preparing radioactive enzymes for study of their catabolism.


Simultaneous differential spinning disk fluorescence optical sectioning microscopy and nanomechanical mapping atomic force microscopy.
Combined microscopy techniques offer the life science research community a powerful tool to investigate complex biological systems and their interactions. Here, we present a new combined microscopy platform based on fluorescence optical sectioning microscopy through aperture correlation microscopy with a Differential Spinning Disk (DSD) and nanomechanical mapping with an Atomic Force Microscope (AFM). The illumination scheme of the DSD microscope unit, contrary to standard single or multi-point confocal microscopes, provides a time-independent illumination of the AFM cantilever. This enables a distortion-free simultaneous operation of fluorescence optical sectioning microscopy and atomic force microscopy with standard probes. In this context, we discuss sample heating due to AFM cantilever illumination with fluorescence excitation light. Integration of a DSD fluorescence optical sectioning unit with an AFM platform requires mitigation of mechanical noise transfer of the spinning disk. We identify and present two solutions to almost annul this noise in the AFM measurement process. The new combined microscopy platform is applied to the characterization of a DOPC/DOPS (4:1) lipid structures labelled with a lipophilic cationic indocarbocyanine dye deposited on a mica substrate.


Obesity increases metabolic syndrome risk factors in school-aged children from an urban school in Mexico city.
To characterize the nutritional status of school-aged children from an urban public school in Mexico City, Mexico, and to assess the influence of obesity on health status in a subgroup of these children. Cross-sectional descriptive study. A nutrition screening was done for all children, including anthropometric (ie, weight, height, and waist circumference) and blood pressure assessment. In the subgroup of children, complementary dietary and biochemical assessment (ie, glucose, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride, insulin, albumin, hemoglobin, and hematocrit levels) was done. Children from an urban school in Mexico City (N=561) aged 6 to 13 years. The representative subgroup (n=88) was selected based on age (9 to 12 years) and weight status (ie, normal, overweight, or obese). Descriptive statistics, correlations, mean differences tests (analysis of variance, Kruskal-Wallis and Mann-Whitney U), and chi(2) tests (categorical variables) were done with SPSS version 13 (2005, SPSS Inc, Chicago, IL). In the whole school, overweight and obesity prevalence were 27.1% and 21.4%, respectively. High systolic blood pressure was seen in 8.4% of children and 6.2% of children had prehypertension. Higher hypertension risk was seen in children with body mass index > or =95th percentile and waist circumference > or =90th percentile (88 cm). Significantly higher waist circumference, systolic blood pressure, insulin resistance indexes, and triglyceride levels were found among the obese when compared with normal-weight children. Childhood obesity prevalence is high in Mexico and it is having an influence on children's health. It is urgent to design, implement, and evaluate specific childhood obesity prevention programs.


Does the duration of lysis affect the sensitivity of the in vitro alkaline comet assay?
The alkaline comet assay is now the method of choice for measuring different kinds of DNA damage in cells. Several attempts have been made to identify and evaluate the critical points affecting the comet assay outcome, highlighting the requirement of arriving at a standardised protocol in order to be able to compare the results obtained in different laboratories. However, reports on the effect of modifying the time of lysis are lacking. Here we tested different times of lysis (from no lysis to 1 week) in control HeLa cells and HeLa cells treated with different concentrations of methyl methanesulfonate (MMS) or H2O2. We also tested different times of lysis in the comet assay combined with formamidopyrimidine DNA glycosylase (FPG) in untreated and Ro 19-8022 plus light-treated HeLa cells. The same DNA damage levels were detected in the absence of lysis or after 1h of lysis when the standard comet assay was used to detect the MMS- and H2O2-induced lesions; the response increased when longer lysis was used, up to at least 1 week. When FPG was used, a minimum lysis period of 5 min was necessary to allow the enzyme to reach the DNA; the same DNA damage levels were detected after 5 min or 1h of lysis and the response increased up to 24h. In conclusion, the time of lysis can be varied depending on the sensitivity needed in both versions of the assay, and a constant time of lysis should be used if results from different experiments or laboratories are to be compared.


Attachment and Personality Disorders Among Child Molesters: The Role of Trust.
The present study investigated multivariate associations between attachment styles and personality disorders (PDs)-and the mediating role of trust-in a sample of child molesters ( n = 84) and a matched control group from the general community ( n = 80). Among child molesters, canonical correlation analysis revealed that two variates resembling avoidant and anxious attachment dimensions were associated with PD traits. Attachment avoidance was related to schizoid, schizotypal, and avoidant PDs, with a marginal contribution of antisocial PD. Attachment anxiety was related to borderline and histrionic PDs, with a marginal contribution of obsessive-compulsive PD. Paranoid and dependent PDs contributed to both variates. In the control group, a more general association between attachment insecurity and PDs emerged. Finally, mistrust significantly explained the associations between attachment and PDs in both samples. Future studies should examine whether treatment for PDs in child molesters could benefit from a focus on attachment and trust.


The cycloaddition of nitrones with homochiral cyclopropanes.
The cycloaddition of nitrones and enantiomerically pure cyclopropane-1,1-dicarboxylates is examined. Transfer of optical activity to the adduct is dictated by thermal reaction conditions and nature of cyclopropane substitution. Optically active 2-substituted cyclopropane-1,1-dicarboxylates are shown to racemize under typical reaction conditions, providing evidence for a zwitterionic ring-opened intermediate.


Carbon dots as naked eye sensors.
Optical sensors are always fascinating for chemists due to their selectivity, sensitivity, robustness and cost-effective nature. Moreover, these sensors provide the facility of onsite detection without employing any instrumental technique. A number of such visual sensors including carbon dots (CDs) have been reported for selective detection of many ionic and molecular species. This review elaborates the utilization of CDs as colorimetric sensors. Carbon dots (CDs) are being synthesized from a large number of natural and synthetic carbon source materials using a variety of methods. CDs can also be tuned chemically by doping, to impart the desired sensing properties. Therefore, the development of CDs with selective sensing properties enables extremely low detection limits and has thus gained substantial attention.


Multipoint Suture Fixation Technique for Abdominal Wall Reconstruction with Component Separation and Onlay Biological Mesh Placement.
Component separation with mesh reinforcement has become the primary modality for complex abdominal wall reconstruction. However, many fundamental questions remain unanswered, such as whether underlay versus overlay mesh placement is superior, and what is the best means of suture fixation technique for mesh placement? This study presents the senior author's technique for onlay biologic mesh placement with multipoint suture fixation in combination with component separation and its subsequent low recurrence rates. This is a retrospective review of the senior author's cases of component separation with onlay biologic mesh placement during his tenure at the home institution of the University of Alabama at Birmingham. A total of 75 patients were included, all of whom underwent complex abdominal wall reconstruction from September 2002 to April 2012. Patients were excluded from the dataset if their surgery occurred less than two years before date of data collection to give a minimum 2-year follow-up. Patients were identified by Current Procedural Terminology codes for component separation and their charts reviewed by the home institution's electronic medical record. Data point entries included patient demographics and comorbidities, concomitant procedures such as bowel resection or panniculectomy, and characteristics of the reconstruction such as type of mesh used. Primary data endpoints were complications following surgery, particularly recurrence and laxity. A total of 75 patients were included in the study from September 2002 to April 2012 with a minimum 2-year follow-up period. The recurrence rate was 13 per cent and the rate of laxity 2.7 per cent. There was one death (1.35%). The most frequent complication was seromas at a rate of 17 per cent. Multipoint fixation suture technique for abdominal wall reconstruction with component separation and onlay biologic mesh is a reproducible technique with reliably low recurrence rates.