Identification of Biomarkers for Cervical Cancer Radiotherapy Resistance Based on RNA Sequencing Data.
Cervical cancer as a common gynecological malignancy threatens the health and lives of women. Resistance to radiotherapy is the primary cause of treatment failure and is mainly related to difference in the inherent vulnerability of tumors after radiotherapy. Here, we investigated signature genes associated with poor response to radiotherapy by analyzing an independent cervical cancer dataset from the Gene Expression Omnibus, including pre-irradiation and mid-irradiation information. A total of 316 differentially expressed genes were significantly identified. The correlations between these genes were investigated through the Pearson correlation analysis. Subsequently, random forest model was used in determining cancer-related genes, and all genes were ranked by random forest scoring. The top 30 candidate genes were selected for uncovering their biological functions. Functional enrichment analysis revealed that the biological functions chiefly enriched in tumor immune responses, such as cellular defense response, negative regulation of immune system process, T cell activation, neutrophil activation involved in immune response, regulation of antigen processing and presentation, and peptidyl-tyrosine autophosphorylation. Finally, the top 30 genes were screened and analyzed through literature verification. After validation, 10 genes (KLRK1, LCK, KIF20A, CD247, FASLG, CD163, ZAP70, CD8B, ZNF683, and F10) were to our objective. Overall, the present research confirmed that integrated bioinformatics methods can contribute to the understanding of the molecular mechanisms and potential therapeutic targets underlying radiotherapy resistance in cervical cancer.


Evaluation of the Polymer Modified Tack Coat on Aged Concrete Pavement: An Experimental Study on Adhesion Properties.
This study addresses the challenges of overlaying old concrete pavement with asphalt by introducing a new trackless tack coat material containing polymer. The aim is to enhance the durability of asphalt concrete overlay pavement on old cement concrete pavement. It contributes to the development of improved construction techniques for pavement rehabilitation and highlights the need for reliable adhesion performance evaluation based on different spray amounts and surface conditions. Additionally, to evaluate the effect of the adhesion performance based on the spraying amount, a tensile adhesion test was conducted by applying spray amounts of 0.30, 0.45, and 0.60 l/m2 on different surface conditions. The basic and adhesion performances of the polymer-modified tack coat material are evaluated through direct tensile and shear bond strength tests. The test outcomes demonstrated that the newly developed polymer-modified tack coat material had considerably greater adhesion strength compared to the traditional rapid-setting products. Its adhesive strength was 1.68 times higher on concrete and 1.78 times higher on asphalt. The new trackless tack coat material exhibited an adhesion performance of 1.05 MPa in direct tensile strength at 0.45 l/m2, which was 1.21 times higher than the rapid-setting tack coat. Results also confirmed that the new tack coat material exhibits values 1.90 times greater than the conventional rapid-setting tack coat material in shear bond strength, respectively. By simulating the process of separation and re-adhesion of pavement layers caused, the new tack coat material shows a tensile adhesion strength of 63% of the original state, which is advantageous for securing the durability of the pavement. Overall, the newly developed polymer-modified trackless tack coat has been shown to effectively enhance the adhesion performance between pavement layers without process delay, highlighting the potential of the new tack coat material to enhance the durability of asphalt concrete overlay pavement on old cement concrete pavement.


Evaluation of the effect of the feeding regime on the removal of metals and pathogens in microalgae-bacterial systems.
Microalgae-bacteria systems are used for the treatment of effluents, using a technology that has stood out with excellent results, as reported in the literature. However, investigating these systems in more depth can improve our understanding of the removal mechanisms for a wide range of existing and emerging pollutants and help improve the guidelines for design and operation, in order to improve the treatment efficiency as well as biomass productivity. This work studied the impact of the feeding regime on the removal of metals and pathogens from primary domestic wastewater in high rate algal ponds (HRAPs). For this, one reactor was fed continuously (HRAP1) while two reactors were fed in semi-continuous mode, during 12 h day-1 (HRAP2) and 0.1 h day-1 (HRAP3). Although removal efficiencies of 82 ± 5% for Mn and 90% for E. coli were reached in the semi-continuously fed reactors, there was no significant difference between the conditions studied. On the other hand, for biomass productivity, the semi-continuous feeding regime was more advantageous with a growth of ≈ 22 mg L-1 day-1.


Investigation and characterization of receptors for pituitary adenylate cyclase-activating polypeptide in human brain by radioligand binding and chemical cross-linking.
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a novel peptide of hypothalamic origin which increases adenylate cyclase activity in rat anterior pituitary cell cultures. The 38-amino acid peptide shows a close sequence homology to vasoactive intestinal peptide (VIP). Binding sites for PACAP in membranes from postmortem human brain tissue were studied using [125I]PACAP27 as the radioligand. High specific binding sites (amount of specific binding measured at 0.25 nM [125I]PACAP27 in femtomoles per mg protein +/- SEM; n = 4) were present in hypothalamus (344.5 +/- 13.0), brain stem (343.0 +/- 29.3), cerebellum (292.0 +/- 21.1), cortex (259.6 +/- 19.8), and basal ganglia (259.2 +/- 50.3). Specific binding sites in pituitary, although present, were less abundant (35.0 +/- 8.9). Binding of [125I]PACAP27 was reversible and time, pH, and temperature dependent. Despite the homology with VIP, VIP was a poor inhibitor of [125I]PACAP27 binding (IC50, greater than 1 microM) compared with PACAP27 (IC50, 0.5-1.3 nM) and PACAP38 (IC50, 0.2-1.3 nM). Scatchard plots of [125I]PACAP27 binding showed the presence of both high and lower affinity sites. Chemical cross-linking of PACAP-binding sites revealed that [125I]PACAP27 was bound to polypeptide chains of 67,000 and 48,000 mol wt. Thus, we have demonstrated the presence of PACAP-specific receptors in human brain which are not VIP receptors. This opens the possibility of PACAP functioning as a novel neurotransmitter/neuromodulator in human brain.


Pregnancy after perinatal loss: the relationship between anxiety and prenatal attachment.
To determine the difference between levels of pregnancy-specific anxiety and prenatal attachment in a group of pregnant women who previously had a late pregnancy loss and a group of primiparous women of similar gestational age. To also determine the relationship, if any, between anxiety and prenatal attachment in both groups. A nonrandom, comparative descriptive design. Participants recruited from medical offices, childbirth classes, and perinatal support groups and newsletters. A convenience sample of 31 expectant mothers (15 primiparae and 16 who previously experienced a late pregnancy miscarriage, stillbirth, or neonatal death). Both groups of women were in the 2nd or 3rd trimester of their current pregnancy. Anxiety was measured using the Pregnancy Outcome Questionnaire; prenatal attachment was measured using the Prenatal Attachment Inventory. The loss group showed significantly greater levels of anxiety and significantly lower levels of prenatal attachment compared with a group of primiparous women of a similar gestational age. Women who experienced a previous late pregnancy loss had a higher level of anxiety related to concerns about the pregnancy and decreased prenatal attachment with the child in the current pregnancy. Women in their first pregnancy had decreased anxiety compared with the loss group. Higher levels of prenatal attachment also were shown in the primiparous group.


APOBEC3 inhibition of mouse mammary tumor virus infection: the role of cytidine deamination versus inhibition of reverse transcription.
The apolipoprotein B editing complex 3 (APOBEC3) family of proteins is a group of intrinsic antiviral factors active against a number of retroviral pathogens, including HIV in humans and mouse mammary tumor virus (MMTV) in mice. APOBEC3 restricts its viral targets through cytidine deamination of viral DNA during reverse transcription or via deaminase-independent means. Here, we used virions from the mammary tissue of MMTV-infected inbred wild-type mice with different allelic APOBEC3 variants (APOBEC3(BALB) and APOBEC3(BL/6)) and knockout mice to determine whether cytidine deamination was important for APOBEC3's anti-MMTV activity. First, using anti-murine APOBEC3 antiserum, we showed that both APOBEC3 allelic variants are packaged into the cores of milk-borne virions produced in vivo. Next, using an in vitro deamination assay, we determined that virion-packaged APOBEC3 retains its deamination activity and that allelic differences in APOBEC3 affect the sequence specificity. In spite of this in vitro activity, cytidine deamination by virion-packaged APOBEC3 of MMTV early reverse transcription DNA occurred only at low levels. Instead, the major means by which in vivo virion-packaged APOBEC3 restricted virus was through inhibition of early reverse transcription in both cell-free virions and in vitro infection assays. Moreover, the different wild-type alleles varied in their ability to inhibit this step. Our data suggest that while APOBEC3-mediated cytidine deamination of MMTV may occur, it is not the major means by which APOBEC3 restricts MMTV infection in vivo. This may reflect the long-term coexistence of MMTV and APOBEC3 in mice.


Speech perception at the interface of neurobiology and linguistics.
Speech perception consists of a set of computations that take continuously varying acoustic waveforms as input and generate discrete representations that make contact with the lexical representations stored in long-term memory as output. Because the perceptual objects that are recognized by the speech perception enter into subsequent linguistic computation, the format that is used for lexical representation and processing fundamentally constrains the speech perceptual processes. Consequently, theories of speech perception must, at some level, be tightly linked to theories of lexical representation. Minimally, speech perception must yield representations that smoothly and rapidly interface with stored lexical items. Adopting the perspective of Marr, we argue and provide neurobiological and psychophysical evidence for the following research programme. First, at the implementational level, speech perception is a multi-time resolution process, with perceptual analyses occurring concurrently on at least two time scales (approx. 20-80 ms, approx. 150-300 ms), commensurate with (sub)segmental and syllabic analyses, respectively. Second, at the algorithmic level, we suggest that perception proceeds on the basis of internal forward models, or uses an 'analysis-by-synthesis' approach. Third, at the computational level (in the sense of Marr), the theory of lexical representation that we adopt is principally informed by phonological research and assumes that words are represented in the mental lexicon in terms of sequences of discrete segments composed of distinctive features. One important goal of the research programme is to develop linking hypotheses between putative neurobiological primitives (e.g. temporal primitives) and those primitives derived from linguistic inquiry, to arrive ultimately at a biologically sensible and theoretically satisfying model of representation and computation in speech.


Hepatitis C Virus and Human Cytomegalovirus-Natural Killer Cell Subsets in Persistent Viral Infections.
Hepatitis C virus (HCV) and human cytomegalovirus (HCMV) are prominent examples of RNA and DNA viruses, respectively, that establish a persistent infection in their host. HCV affects over 185 million patients worldwide, who are at high risk for developing liver fibrosis, liver cirrhosis, and ultimately hepatocellular carcinoma. Recent breakthroughs in HCV therapy, using direct-acting antivirals have provided the opportunity to monitor natural killer (NK) cells after clearance of a chronic infection. There is now increasing evidence that the individual NK cell repertoire before infection is predictive for the course of disease. HCMV affects the majority of the global population. While being asymptomatic in healthy individuals, HCMV represents a severe clinical challenge in immunocompromised patients. Both viral infections, HCV and HCMV, lead to long-lasting and profound alterations within the entire NK cell compartment. This review article, will discuss the diverse range of changes in the NK cell compartment as well as potential consequences for the course of disease.


Inhibition of the constitutive activity of human 5-HT1A receptors by the inverse agonist, spiperone but not the neutral antagonist, WAY 100,635.
At recombinant human 5-hydroxytryptamine (5-HT)5-HT1A receptors expressed in Chinese hamster ovary cells (CHO-5-HT1A), 5-carboxamidotryptamine (5-CT), acted as a full agonist (relative to 5-HT = 100%) for stimulation of receptor-mediated [35S]-GTP gamma S (guanylyl 5'-[gamma-thio]-tryphosphate) binding. In contrast, spiperone inhibited basal [35S]-GTP gamma S binding by 30.2% (IC50 = 55.5 nM) in CHO-5-HT1A membranes but not in control untransfected membranes. The antagonist, N-[2-[4-(2-methoxyphenyl) -1-piperazinyl]ethyl]-N-(2-pyridinyl)-cyclohexane-carboxamide (WAY 100,635), blocked both 5-CT-induced stimulation and spiperone-induced inhibition of [35S]-GTP gamma S binding without itself modifying [35S]-GTP gamma S binding. It is concluded that, in this heterologous expression system, 5-HT1A receptors display 'constitutive' activation of G-proteins and that spiperone displays inverse agonist activity whereas WAY 100,635 acts as a 'neutral' antagonist at this site.


The Ã-state dissociation continuum of NO-Ar and its near infrared spectrum.
After preparing NO-Ar in a vibrational state correlating with the first overtone vibration in NO, we recorded its hot band UV spectrum by monitoring simultaneously the intensity in the NO(+) and the NO(+)-Ar ion channels. In this way, the bound as well as the continuous part of the electronic Ã←X̃ spectrum are observed directly. Below the dissociation threshold, the intensity is found exclusively in the NO(+)-Ar ion channel while above it is found in the NO fragment ion channel. We observe simultaneously intensity in both ion channels only for a very narrow frequency range near the dissociation threshold. Structures in the dissociation spectrum correlate well with the thresholds for production of NO(A) in different rotational states. At frequencies well above the dissociation threshold, NO-Ar is detected efficiently as a NO fragment. This fact has been exploited to record the near IR spectrum of NO-Ar with significantly increased sensitivity. The dissociation detected spectra are essentially identical to our previous constant photon energy sum (CONPHOENERS) scans [B. Wen, Y. Kim, H. Meyer, J. Kłos, and M. H. Alexander, J. Phys. Chem. A 112, 9483 (2008)]. Several hot band spectra have been remeasured with improved sensitivity enabling a comprehensive analysis yielding for the first time spectroscopic constants for levels associated with the potential surfaces of NO-Ar correlating with NO(v(NO) = 0 and 2). Since many NO-X complexes do not have a strong bound Ã-state spectrum, although they do have a Ã-state dissociation continuum, there is the possibility to record their near IR spectra by employing dissociation detection.


Influence of High Polyphenol Beverage on Stress-Induced Platelet Activation.
Platelets are playing a crucial role in acute cardiovascular events. We investigated if physical stress activates platelets and whether this activation can be inhibited by a polyphenol-enriched diet. Blood samples were taken from a total of 103 athletes three weeks before, one day before, immediately as well as 24 hours and 72 hours after a marathon run. Participants were randomized, double-blinded and divided into two groups. One group received a polyphenol-rich beverage the other the same beverage without polyphenols. Besides analysis of platelet counts and impedance-aggregometric-measurement of platelet activity, soluble P-selectin and Endothelin-A measurements were performed. In the control group, runners showed a 2.2-fold increased platelet aggregation directly after completing a marathon and within the following three days when compared with baseline values (p<0.01). In accordance, significant increases in sP-selectin (57.52ng/ml vs. 94.86ng/ml;p<0.01) were detectable. In contrast, for the group consuming a beverage with increased polyphenol content (upper quartile of study beverage intake) we did not find any increase of platelet aggregation. Physical stress causes a significant increase in platelet activity. Our results demonstrate that a diet enriched in polyphenols is capable of preventing platelet activation. These findings might indicate a diminished cardiovascular stress-reaction following pre-exposition to polyphenol-enriched diet.


Raupp: 50 years of neuroradiology.
Evaluate the laboral and intellectual contributions of a founder of Brazilian Neuroradiology to the development of specialty. Interviews were conducted with Dr. Raupp and contemporary doctors. Then we made a literature review with the Raupp search term aiming to identify those papers which included major changes in the diagnostic and therapeutic neurosurgical. The colleagues consulted were unanimous in recognizing the work of avant-garde and the importance of Dr. Raupp to the development of neuroradiological methods, especially in the pre-computed tomography fase. The work of Dr. Raupp was fundamental for the consolidation of Brazilian Neuroradiological School over the past five decades. He developed diagnostic and therapeutic techniques in congruence with the practices of the specialty on the global stage and he promoted education through medical residency programs.


Fabrication and Study of Dextran/Sulfonated Polysulfone Blend Membranes for Low-Density Lipoprotein Adsorption.
The abnormal increase in low-density lipoprotein (LDL) in human blood is a main independent risk factor for the pathogenesis of atherosclerosis, whereas a reduced LDL level effectively lowers morbidity. It is important to develop LDL adsorption materials with high efficiency and selectivity, as well as to simplify their fabrication processes. In this paper, polysulfone (PSF), sulfonated polysulfone (SPSF), and sulfonated polysulfone/dextran (SPSF/GLU) membranes were successfully fabricated for LDL adsorption using a solution casting technique. Attenuated total reflectance Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy measurements confirmed the success of the preparation. The water contact angle decreased from 89.7 ± 3.4° (PSF) to 76.4 ± 3.2° (SPSF) and to 71.2 ± 1.9° (SPSF/GLU), respectively. BSA adsorption testing showed that the SPSF/GLU with surface enrichment of sulfonate groups and glycosyl groups possessed higher resistance to protein solution. The adsorption and desorption behaviors of the studied samples in single-protein or binary-protein solutions were systematically investigated by enzyme-linked immunosorbent assay (ELISA), The results showed that SPSF/GLU, which had excellent resistance to protein adsorption, possessed a similar adsorption capacity to that of PSF. SPSF membrane exhibited excellent selective affinity for LDL in single and binary protein solutions, suggesting potential applications in LDL removal.


Assessment of the Feasibility and Acceptability of Using Water Pasteurization Indicators to Increase Access to Safe Drinking Water in the Peruvian Amazon.
Approximately two billion people lack access to microbiologically safe drinking water globally. Boiling is the most popular household water treatment method and significantly reduces diarrheal disease, but is often practiced inconsistently or ineffectively. The use of low-cost technologies to improve boiling is one approach with potential for increasing access to safe drinking water. We conducted household trials to evaluate the feasibility and acceptability of water pasteurization indicators (WAPIs) in the Peruvian Amazon in 2015. A total of 28 randomly selected households were enrolled from a rural and a peri-urban community. All households trialed two WAPI designs, each for a 2-week period. Ninety-six percent of participants demonstrated the correct use of the WAPIs at the end of each trial, and 88% expressed satisfaction with both WAPI models. Ease of use, short treatment time, knowledge of the association between WAPI use and improved health, and the taste of treated water were among the key factors that influenced acceptability. Ease of use was the key factor that influenced design preference. Participants in both communities preferred a WAPI with a plastic box that floated on the water's surface compared with a WAPI with a wire that was dipped into the pot of drinking water while it was heating (77% versus 15%, P < 0.001); we selected the box design for a subsequent randomized trial of this intervention. The high feasibility and acceptability of the WAPIs in this study suggest that these interventions have potential to increase access to safe water in resource-limited settings.


Reevaluation, using marker enzymes, of the ability of saponin and ammonium chloride to free Plasmodium from infected erythrocytes.
Saponin and ammonium chloride lysis have been applied for some time to the separation of erythrocyte membranes from malarial-infected erythrocytes, allowing easy isolation of the parasites. We present a reevaluation of the use of saponin and ammonium chloride as tools for isolating Plasmodium (knowlesi or falciparum) parasites. Acetylcholine esterase (EC 220.127.116.11) was used as an erythrocyte membrane marker and CDP-choline: 1,2-diacylglycerol cholinephosphotransferase (EC 184.108.40.206) as a parasite membrane marker to monitor fractionation by these agents. Both saponin and ammonium chloride produced hemolysis of uninfected and infected erythrocytes, but failed to separate host erythrocyte membrane from the parasite, regardless of its stage. Thus, saponin and ammonium chloride can be used to isolate whole infected erythrocytes, depleted of hemoglobin, by selective disruption of uninfected cells.


Validation of a partial coherence interferometry method for estimating retinal shape.
To validate a simple partial coherence interferometry (PCI) based retinal shape method, estimates of retinal shape were determined in 60 young adults using off-axis PCI, with three stages of modeling using variants of the Le Grand model eye, and magnetic resonance imaging (MRI). Stage 1 and 2 involved a basic model eye without and with surface ray deviation, respectively and Stage 3 used model with individual ocular biometry and ray deviation at surfaces. Considering the theoretical uncertainty of MRI (12-14%), the results of the study indicate good agreement between MRI and all three stages of PCI modeling with <4% and <7% differences in retinal shapes along horizontal and vertical meridians, respectively. Stage 2 and Stage 3 gave slightly different retinal co-ordinates than Stage 1 and we recommend the intermediate Stage 2 as providing a simple and valid method of determining retinal shape from PCI data.


Compound elevated skull fractures: Review of literature.
Compound elevated skull fractures (CESF) are rare traumatic injuries. To date, only 27 cases have been reported. The authors report three cases of CESF managed at their institute. All were middle-aged males. The mechanism was assault by sharp-edged objects in two and road traffic accident (RTA) in one case. One underwent simple suturing; debridement and decompressive craniectomy was done in the remaining two cases. Good and poor outcomes were noted in one case each, while one died. A literature review was performed to analyse all cases of CESF reported in English literature. Including this one, a total of 30 cases were analysed. Mean age was 25.2 years, of which seven were aged < 18 years. There were 12 mild, five moderate, 11 severe HI cases and two cases were not detailed. Underlying injuries were seen in ~ 2/3 of cases. All, except two cases, underwent definitive surgery in the form of debridement with/without haematoma removal. Good-to-excellent outcomes were noted in 2/3 cases. There were 6/30 (20%) deaths noted. CNS infections and poor admission GCS were associated with increased mortality rates. CESF are rare injuries. Early surgery in the form of debridement with broad-spectrum antibiotic coverage is recommended to prevent infectious complications and improve outcome. Outcome is dependent on three main factors-admission GCS score, intactness of duramater and post-operative CNS infections.


Partial-mouth periodontal examination protocols for the determination of the prevalence and extent of gingival bleeding in adolescents.
To compare the performance of partial-mouth periodontal examination (PMPE) protocols with different cut-off points to the full-mouth examination (FME) in the assessment of the prevalence and extent of gingival bleeding in adolescents. A cross-sectional study was conducted involving 12-year-old adolescents. Following a systematic two-stage cluster sampling process, 1134 individuals were evaluated. Different PMPE protocols were compared to the FME with six sites per tooth. Sensitivity, specificity, area under the ROC curve (AUC), intraclass correlation coefficient (ICC), relative and absolute biases and the inflation factor were assessed for each PMPE protocol with different cut-off points for the severity of gingival bleeding. The highest AUC values were found for the six-site two-diagonal quadrant (2-4) (0.97), six-site random half-mouth (0.95) and Community Periodontal Index (0.95) protocols. The assessment of three sites [mesiobuccal (MB), buccal (B) and distolingual (DL)] in two diagonal quadrants and the random half-mouth protocol had higher sensitivity and lower specificity than the same protocols with distobuccal (DB) sites. However, the use of DB sites led to better specificity and improved the balance between sensitivity and specificity, except for the two-diagonal quadrant (1-3) protocol. The ≥1 cut-off point led to the most discrepant results from the FME. Six-site two-diagonal quadrant (2-4) and random half-mouth assessments perform better in the evaluation of gingival bleeding in adolescents. However, when a faster protocol is needed, a two-diagonal quadrant assessment using only MB, B and DL sites can be used with no important loss of information.


Factors Influencing the Phenotypic Expression of Hypertrophic Cardiomyopathy in Genetic Carriers.
Hypertrophic cardiomyopathy (HCM) is a disorder with variable expression. It is mainly caused by mutations in sarcomeric genes but the phenotype could be modulated by other factors. The aim of this study was to determine whether factors such as sex, systemic hypertension, or physical activity are modifiers of disease severity and to establish their role in age-related penetrance of HCM. We evaluated 272 individuals (mean age 49 ± 17 years, 57% males) from 72 families with causative mutations. The relationship between sex, hypertension, physical activity, and left ventricular hypertrophy was studied. The proportion of affected individuals increased with age. Men developed the disease 12.5 years earlier than women (adjusted median, 95%CI, -17.52 to -6.48; P < .001). Hypertensive patients were diagnosed with HCM later (10.8 years of delay) than normotensive patients (adjusted median, 95%CI, 6.28-17.09; P < .001). Individuals who performed physical activity were diagnosed with HCM significantly earlier (7.3 years, adjusted median, 95%CI, -14.49 to -1.51; P = .016). Sex, hypertension, and the degree of physical activity were not significantly associated with the severity of left ventricular hypertrophy. Adjusted survival both free from sudden death and from the combined event were not influenced by any of the exploratory variables. Men and athletes who are carriers of sarcomeric mutations are diagnosed earlier than women and sedentary individuals. Hypertensive carriers of sarcomeric mutations have a delayed diagnosis. Sex, hypertension, and physical activity are not associated with disease severity in carriers of HCM causative mutations.


CREAMMIST: an integrative probabilistic database for cancer drug response prediction.
Extensive in vitro cancer drug screening datasets have enabled scientists to identify biomarkers and develop machine learning models for predicting drug sensitivity. While most advancements have focused on omics profiles, cancer drug sensitivity scores precalculated by the original sources are often used as-is, without consideration for variabilities between studies. It is well-known that significant inconsistencies exist between the drug sensitivity scores across datasets due to differences in experimental setups and preprocessing methods used to obtain the sensitivity scores. As a result, many studies opt to focus only on a single dataset, leading to underutilization of available data and a limited interpretation of cancer pharmacogenomics analysis. To overcome these caveats, we have developed CREAMMIST (https://creammist.mtms.dev), an integrative database that enables users to obtain an integrative dose-response curve, to capture uncertainty (or high certainty when multiple datasets well align) across five widely used cancer cell-line drug-response datasets. We utilized the Bayesian framework to systematically integrate all available dose-response values across datasets (>14 millions dose-response data points). CREAMMIST provides easy-to-use statistics derived from the integrative dose-response curves for various downstream analyses such as identifying biomarkers, selecting drug concentrations for experiments, and training robust machine learning models.


Estimation of effective b-value for a diffusion-weighted double-echo steady-state sequence with bipolar gradients.
Diffusion-weighted double-echo steady-state (dwDESS) MRI with bipolar diffusion gradients is a promising candidate to obtain diffusion weighted images (DWI) free of geometric distortions and with low motion sensitivity. However, a wider clinical application of dwDESS is currently hindered as no method is reported to explicitly calculate the effective b-value of the obtained DWI from the diffusion-gradients applied in the sequence. To this end, a previously described signal model was adapted for dwDESS with bipolar diffusion gradients, which allows to estimate an effective b-value, dubbed b'. Evaluation in phantom examinations was performed on a clinical 1.5 T MR system. Experimental results were compared with theoretical predictions, including the apparent diffusion coefficient (ADC) based on b-values from a standard EPI-DWI sequence and ADC' based on the effective b' from the dwDESS sequence. The adapted signal model was able to describe the experimental results, and the obtained values of ADC' were in line with conventional ADC measurements.


The association between Harris lines and enamel hypoplasia in prehistoric California Indians.
Hypoplastic defects of tooth enamel and Harris lines in the long bones have been heralded as potentially useful indicators of health conditions in prehistoric populations. Both result from temporary cessation of growth processes due to similar types of disease, malnutrition, or other metabolic insult. An association test for the first six years of life was conducted on a large series of prehistoric California Indians, using femora and canines from young adults. No significant association was found. This is ascribable to differences in etiology and stability.


Flow Focusing: a versatile technology to produce size-controlled and specific-morphology microparticles.
The Flow Focusing platform is especially advantageous for micro- and nanoparticle production. This versatile technique is amenable to designing the size, surface treatment and internal topology of the particles; mechanical stresses are minimal-an optimal feature for the manipulation of delicate substances. Multiplexing and high-rate production are readily implemented. Adaptive operational design can lead, in one single step, to finely tuned microcapsules encasing different products within a targeted morphology. This achievement is of great significance for most microcapsule applications in the biosciences (for example, drug delivery, cell encapsulation, and the production of bead arrays).


Morbidity and mortality in relation to blood pressure and antihypertensive treatment. A 12-year follow-up study of a population sample of Swedish women.
Morbidity and mortality in cardiovascular and cerebrovascular diseases and total mortality have been studied in a longitudinal population study initially comprising 1462 women representative of the general female population. When related to the initial blood pressure (BP) levels of women not on antihypertensive drugs (hypertensives and non-hypertensives), the distributions of women with myocardial infarction (MI) and stroke during the 12-year follow-up period seemed to be U-shaped, with the highest incidences in women with the lowest and the highest BP levels. Women recognized as untreated hypertensives in the initial study were offered regular control by the study team during the whole 12-year period and were treated when treatment was considered indicated. They were found to be similar to the non-hypertensives with regard to the incidence of MI and stroke and total mortality. Our encouraging results may be explained by continuity of medical care, the antihypertensive treatment per se or the types of antihypertensive drugs administered.


Enhanced tomato disease resistance primed by arbuscular mycorrhizal fungus.
Roots of most terrestrial plants form symbiotic associations (mycorrhiza) with soil- borne arbuscular mycorrhizal fungi (AMF). Many studies show that mycorrhizal colonization enhances plant resistance against pathogenic fungi. However, the mechanism of mycorrhiza-induced disease resistance remains equivocal. In this study, we found that mycorrhizal inoculation with AMF Funneliformis mosseae significantly alleviated tomato (Solanum lycopersicum Mill.) early blight disease caused by Alternaria solani Sorauer. AMF pre-inoculation led to significant increases in activities of β-1,3-glucanase, chitinase, phenylalanine ammonia-lyase (PAL) and lipoxygenase (LOX) in tomato leaves upon pathogen inoculation. Mycorrhizal inoculation alone did not influence the transcripts of most genes tested. However, pathogen attack on AMF-inoculated plants provoked strong defense responses of three genes encoding pathogenesis-related proteins, PR1, PR2, and PR3, as well as defense-related genes LOX, AOC, and PAL, in tomato leaves. The induction of defense responses in AMF pre-inoculated plants was much higher and more rapid than that in un-inoculated plants in present of pathogen infection. Three tomato genotypes: a Castlemart wild-type (WT) plant, a jasmonate (JA) biosynthesis mutant (spr2), and a prosystemin-overexpressing 35S::PS plant were used to examine the role of the JA signaling pathway in AMF-primed disease defense. Pathogen infection on mycorrhizal 35S::PS plants led to higher induction of defense-related genes and enzymes relative to WT plants. However, pathogen infection did not induce these genes and enzymes in mycorrhizal spr2 mutant plants. Bioassays showed that 35S::PS plants were more resistant and spr2 plants were more susceptible to early blight compared with WT plants. Our finding indicates that mycorrhizal colonization enhances tomato resistance to early blight by priming systemic defense response, and the JA signaling pathway is essential for mycorrhiza-primed disease resistance.


Prevalence of obesity and contributing factors among Sherpa women in urban and rural Nepal.
Dietary and lifestyle changes have profound influences on the body mass and nutritional status of individuals living in developed countries. This report used data from a prospective longitudinal study to assess the prevalence of obesity among Sherpa women and to determine which factors were most predictive of it. The body mass index (BMI), energy consumption and expenditures, and physical activity patterns were compared for nonpregnant, premenopausal women living in urban low altitude (n = 216); urban high altitude (n = 56); and rural high altitude (n = 93) settings. Area of residence was highly predictive of the BMI. The mean body weight and BMI were significantly higher for the urban low altitude sample (53.3 kg and 23.5 kg/m2 , respectively) than for the total high altitude sample (51.4 kg and 21.8 kg/m2 , respectively). The rural, high altitude sample had the lowest mean body weight (50.1 kg), triceps skinfold (18.5 mm), and BMI (21.3 kg/m2 ). Although mean BMI was in the range associated with the overall lowest risk to health, distribution of the BMI showed that 29% of the urban low altitude sample were classified obese. The prevalence of obesity was correlated with reduced energy expenditure, not to an increase in consumed calories. Reduced energy expenditures appear to be related to shifts in occupation, access to motorized transportation, and increased affluence, which has allowed Sherpas to hire servants to do manual labor. These data suggest that Sherpa women may potentially be at risk of chronic health problems in the future because of increased adiposity. Am. J. Hum. Biol. 10:519-528, 1998. © 1998 Wiley-Liss, Inc.


Interacting Electrons in Graphene: Fermi Velocity Renormalization and Optical Response.
We have developed a Hartree-Fock theory for electrons on a honeycomb lattice aiming to solve a long-standing problem of the Fermi velocity renormalization in graphene. Our model employs no fitting parameters (like an unknown band cutoff) but relies on a topological invariant (crystal structure function) that makes the Hartree-Fock sublattice spinor independent of the electron-electron interaction. Agreement with the experimental data is obtained assuming static self-screening including local field effects. As an application of the model, we derive an explicit expression for the optical conductivity and discuss the renormalization of the Drude weight. The optical conductivity is also obtained via precise quantum Monte Carlo calculations which compares well to our mean-field approach.


Management of patients with chronic hepatitis B.
Better understanding of hepatitis B virus (HBV) replication and the natural history and immunopathogenesis of chronic hepatitis B, together with the introduction of effective agents with different mechanisms of action, is the basis for better therapeutic strategies against chronic hepatitis B. Substantial experience has now been accumulated in the use of some of these drugs, and an Asia-Pacific Consensus has been reached on indications for their use. The goals of therapy and aspects of general management will be reviewed here. Among currently available drugs, alpha-interferon therapy gives a response rate (hepatitis B e antigen (HBeAg) seroconversion) of 30-40% compared with 10-20% in matched controls, but patients with lower alanine aminotransferase (ALT), higher HBV-DNA, and immunosuppressed patients have a poorer response, and alpha-interferon can be dangerous in cirrhosis. Meta-analysis of four controlled trials also suggests that thymosin-alpha1 is effective, but more studies are needed. Lamivudine has been most extensively studied. It is effective in terms of HBV-DNA loss, ALT normalization, HBeAg seroconversion, and improvement in histology, as well as being well tolerated. After 1 year of treatment, HBeAg seroconversion rate increased with higher pretherapy ALT levels, suggesting that patients with stronger endogenous antiviral defenses to kill hepatocytes harboring covalently closed circular DNA have a better response to direct antiviral effects. Lamivudine is also beneficial in HBeAg negative chronic hepatitis B, and patients with decompensated cirrhosis and HBV replication. However, genotypic-resistant tyrosine-methionine-aspartate-aspartate (YMDD) mutations start to emerge after 9-10 months of lamivudine therapy, and their incidence increases more quickly than the HBeAg seroconversion rate durating prolonged therapy. Thus the benefits of long-term lamivudine must be balanced against concern about YMDD mutations, and the durability of treatment response. There are encouraging preliminary results for adefovir dipivoxil, entecavir, emtricitabine, clevudine and other nucleoside/nucleotide analogs in the early stages of appraisal; entecavir and adefovir dipivoxil appear effective in patients with YMDD mutants. Further development of new drugs and new strategies, such as combination or sequential therapy, may help to better achieve the goals of treatment for chronic hepatitis B in the new century.


[Highly polymorphic regions of the genes for apolipoprotein B and angiotensin-converting enzyme in the Udmurt population].
The hypervariable regions of the 3'-end of the apolipoprotein B gene (APOB3'-VNTR) and angiotensin converting enzyme gene (ACE), which had 10-15 alleles each, were studied in a sample from the Udmurt population by means of polymerase chain reaction (PCR). From the literature data, the genetic position of Udmurts among 12 groups of Caucasoid, Mongoloid, and Negroid populations was determined. The data obtained by the method of principal components indicated that Udmurts held an isolated position in the northern branch of the Caucasoid race.


The Effect of Perceiving a Calling on Pakistani Nurses' Organizational Commitment, Organizational Citizenship Behavior, and Job Stress.
People differ considerably in the way in which they express and experience their nursing careers. The positive effects associated with having a calling may differ substantially based on individuals' abilities to live out their callings. In a working world where many individuals have little to no choice in their type of employment and thus are unable to live out a calling even if they have one, the current study examined how perceiving a calling and living a calling interacted to predict organizational commitment, organizational citizenship behavior, and job stress with career commitment mediating the effect of the interactions on the three outcome variables. The purpose of the study is to investigate the mediating effect of career commitment between the relationships of calling and (a) nurses' attitudes (organizational commitment), (b) behaviors (organizational citizenship behavior), and (c) subjective experiences regarding work (job stress). Using a descriptive exploratory design, data were collected from 332 registered nurses working in Pakistani hospitals. Descriptive analysis and hierarchical regression analysis were used for data analysis. Living a calling moderated the effect of calling on career commitment, organizational citizenship behavior, and job stress, and career commitment fully mediated the effect of calling on organizational commitment, organizational citizenship behavior, and job stress. Increasing the understanding of calling, living a calling, and career commitment may increase nurses' organizational commitment and organizational citizenship behavior and decrease job stress. The study provided evidence to help nursing managers and health policy makers integrate knowledge and skills related to calling into career interventions and help nurses discover their calling.


Overexpression of brachyury contributes to tumor metastasis by inducing epithelial-mesenchymal transition in hepatocellular carcinoma.
Brachyury overexpression has been reported in various human malignant neoplasms, but its expression and function in hepatocellular carcinoma progression and metastasis remains unknown. The present study aimed to evaluate the critical role of Brachyury in HCC metastasis. The expression of Brachyury in human HCC (SMMC7721, HepG2, FHCC98, and Hep3B) and control cell lines was analyzed using quantitative reverse-transcriptase polymerase chain reaction and immunoflourence methods. Cancerous tissues collected from patients with HCC (n = 112) were analyzed using immunohistochemical method; a microarray analysis of HCC tissues was performed to explore the clinicopathological variables of HCC. The migratory and invasive capacities of Brachyury-SMMC7721 and Brachyury-HepG2 transfected cells were evaluated using in vitro scratch wound healing and Matrigel invasion assays, respectively. Further, six-week-old male BALB/c nude mice (n = 10) model was used in vivo assay. Elevated expression of Brachyury was detected in HCCs (62.5%) compared with that in adjacent nontumorous tissues. Clinicopathological analysis revealed a close correlation of Brachyury expression with distant metastasis and poor prognosis of HCC. Overexpression of Brachyury promoted epithelial-mesenchymal transition (EMT) and metastasis of HCC cells in vitro and in vivo. Brachyury overexpression enhanced Akt activation by inhibiting phosphatase and tensin homolog (PTEN), which led to subsequent stabilization of Snail, a critical EMT mediator. The study findings suggest that elevated Brachyury facilitates HCC metastasis by promoting EMT via PTEN/Akt/Snail-dependent pathway. Brachyury plays a pivotal role in HCC metastasis and may serve as a novel prognostic biomarker and therapeutic target.


Novel ADAMTS13 mutations in a patient with congenital thrombotic thrombocytopenic purpura.
Congenital thrombotic thrombocytopenic purpura (TTP) is a rare autosomal recessive genetic disorder caused by mutations in the ADAMTS13 gene. Approximately 200 mutations of the ADAMTS-13 gene have been identified, although only a few have been characterized through in vitro expression studies. We conducted an investigation on a male congenital TTP patient with reduced plasma levels of ADAMTS13 activity. DNA sequence analysis revealed two mutations on chromosome 9 (1.9q34.2) in the patient's ADAMTS13 gene. One mutation was a non-synonymous mutation (exon 5: c.A530G: p.Y177C), while the other was a nonsense mutation (exon 21: c.G2651A: p.W884X). Both mutations were found to be heterozygous. The patient's parents had no history of thrombocytopenia or neurological symptoms. DNA sequence analysis showed the patient's father was a heterozygote for the nonsense mutation of the ADAMTS13 gene (exon 21: c.G2651A: p.W884X), while the mother was a heterozygote for the non-synonymous mutation of the ADAMTS13 gene (exon 5: c.A530G: p.Y177C). To investigate the mechanism behind ADAMTS13 deficiency in this patient, wild type (WT), ADAMTS13 p.Y177C, and ADAMTS13 p.W884X were transiently expressed in 293-6E cells. Expression studies revealed a significant reduction in enzyme activity and secretion, although the protease was detected within the cells. The 3D structures of the natural and mutated ADAMTS-13 proteins were partially reconstructed using the Phyre2 web server. The mutation that replaces the tyrosine residue at amino acid position 177 with cysteine may result in decreased steric hindrance and a looser structure. This mutation affects the binding of calcium ions and the secretion of the enzyme from intracellular to extracellular compartments.


Formation of hydroxyl radicals by collapsing ozone microbubbles under strongly acidic conditions.
Hydroxyl radicals are strong oxidants in aqueous solution, reacting rapidly with a wide range of dissolved compounds. In contrast, ozone is a highly selective oxidant. Understanding the process by which ozone is transformed into hydroxyl radicals is important in the treatment of wastewater and drinking water. We use electron spin-resonance spectroscopy to demonstrate that when microbubbles of ozone in strongly acidic aqueous solution collapse, the ozone progressively decomposes and large quantities of hydroxyl radicals are generated. Moreover, the degradation of polyvinyl alcohol, which is ozone resistant, was also observed during the collapse of the microbubbles. These findings indicate that ozone microbubbles are potentially useful in future water-treatment applications.


Molecular Mechanisms of Resistance to Tyrosine Kinase Inhibitors Associated with Hepatocellular Carcinoma.
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death, which can be attributed to the high incidence and first diagnosis at an advanced stage. Tyrosine kinase inhibitors (TKIs), a class of small-molecule targeting drugs, are primarily used for the clinical treatment of HCC after chemotherapy because they show significant clinical efficacy and low incidence of clinical adverse reactions. However, resistance to sorafenib and other TKIs, which can be used to treat advanced HCC, poses a significant challenge. Recent mechanistic studies have shown that epithelial-mesenchymal transition or transformation (EMT), ATP binding cassette (ABC) transporters, hypoxia, autophagy, and angiogenesis are involved in apoptosis, angiogenesis, HCC cell proliferation, and TKI resistance in patients with HCC. Exploring and overcoming such resistance mechanisms is essential to extend the therapeutic benefits of TKIs to patients with TKI-resistant HCC. This review aims to summarize the potential resistance mechanism proposed in recent years and methods to reverse TKI resistance in the context of HCC.


The influence of different modes of ventilation on standing balance of athletes.
The respiratory movements are one of the factors influencing standing balance. Although well-trained athletes have better postural performance compared to untrained men, it's not quite clear, if the formers' upright posture would be more stable during different ventilation modes, maximal voluntary hyperventilation and inspiratory breath-holding. There are no studies on this subject in the available literature. The aim of this study was to investigate an influence of maximal inspiratory breath-holding and maximal voluntary hyperventilation on the standing balance of athletes. We assessed the amplitude and the velocity of postural sway in the athletes (n = 38) and untrained subjects (n = 28) by the force platform. The frequency characteristics of the center of pressure (CP) oscillations' were also analyzed. The amplitude and the frequency of respiratory movements were estimated by the strain gauge. It was found that during quiet breath velocity and frequency of CP oscillations were lower in the athletes. Breath holding led to an increase of velocity and frequency of CP displacement in both groups, increase of these indices was more pronounced in the athletes. Maximal voluntary hyperventilation caused a significant increase of all stabilographic indices in both groups. Increase of frequency and amplitude of respiratory movements were mainly observed during hyperventilation in athletes and it caused an increase of the velocity of CP displacement. Changes of sway amplitude were the same in both groups. Breath holding led to activation of the postural control, which was more pronounced in the athletes. Hyperventilation caused an impairment of the postural stability. The athletes' postural system compensated the impact of hyperventilation more efficiently versus controls, but it was achieved at the expense of greater effort.


[Achievements of tumor surgery in tumors of the esophagus].
In the past the decisive problem influencing the prognosis of esophageal cancer was the high death rate of patients undergoing esophagectomy (approximately 30%). Intensive analysis of the preoperative risk factors, standardization of the operative procedure and improvement of postoperative intensive care have lowered this to an average of 15%, in specialized clinics to 7-8% and in especially selected patients even to 3%. The operation is the best therapeutic procedure for tumors which do not yet extend beyond the muscularis of the esophageal wall and in which less than 5 mediastinal lymph nodes are metastatically involved.


[Value of DCE-MRI and DWI in the differential diagnosis of inflammatory pseudotumor and lymphoma in the lacrimal gland].
Objective: To evaluate the value of dynamic contrast-enhanced MR (DCE-MRI) and diffusion weighted MR (DWI) in differential diagnosis of inflammatory pseudotumor and lymphoma in the lacrimal gland. Methods: In this retrospective study, a total of 24 cases of inflammatory pseudotumor and 22 cases of lymphoma in the lacrimal gland at Beijing Tongren Hospital confirmed by histological results were enrolled from January 2010 to January 2015.DCE-MRI and DWI were performed in these cases, and the type of time-signal intensity curve (time-intensity curve, TIC), the peak contrast index (CIpeak), maximum enhancement ratio (ERmax), washout ratio (WR) and ADC value were analyzed.Differences of these parameters between inflammatory pseudotumor and lymphoma in the lacrimal gland was evaluated by independent samples t test or Mann-Whitney U test.The receiver operating characteristic analysis was used to evaluate the utility of these parameters in discriminating the two diseases. Results: Type of TIC, CIpeak, WR, ERmax and ADC values were statistically different (all P<0.05) between the inflammatory pseudotumor and lymphoma in the lacrimal gland.ERmax, CIpeak and ADC values of inflammatory pseudotumor were greater than those of lymphoma, but the WR values of inflammatory pseudotumor was less than those of lymphoma.The area under the ROC of the CIpeak, WR, ERmax and ADC values was 0.68±0.08, 0.70±0.08, 0.70±0.08, 0.84±0.81 respectively.Using an ADC(b=0, 1000) value of 1.005×10(-3) mm(2)/s as the diagnostic threshold, the sensitivity, specificity and accuracy to differentiate benign lesions from malignant lesions were 84.2%, 65.0% and 75.0% respectively.The diagnostic ability of DWI combined with DCE-MRI was superior to that of DCE-MRI(P=0.000) or DWI alone(P=0.008) with overall sensitivity, specificity and accuracy of 86.3%, 87.5% and 86.9%. Conclusion: DCE-MRI and DWI may improve the diagnostic accuracy in differentiation of the inflammatory pseudotumors and lymphomas in the lacrimal gland, and play an important role in differentiation among them.


Localized polymyositis associated with chronic thyroiditis.
We describe a case of localized polymyositis accompanied by chronic thyroiditis. Computerized tomogram and magnetic resonance imaging (MRI) studies clearly revealed the lesion localized in the left gastrocnemius muscle. MRI was useful in determining the extent and severity of the muscle lesion. Steroid administration was very effective in the treatment of this patient.


A retrospective study of pattern of recurrence after radical surgery for thoracic esophageal carcinoma with or without postoperative radiotherapy.
The present study aimed to investigate the recurrence pattern of thoracic esophageal cancer (TEC) following radical surgery for guiding postoperative radiotherapy (PRT). Patterns of recurrence were analyzed in patients with recurrence for the first time after radical surgery at the First Affiliated Hospital of Anhui Medical University (Anhui, China) from January 2012 to December 2015. A total of 244 patients were reviewed in the study. The mean recurrence time for patients with PRT was >1 month longer than that for patients without PRT. The lymphatic, anastomotic and hematological recurrence ratios were 87.9 vs. 69.2%, 4.0 vs. 11.5% and 8.0 vs. 17.2%, respectively for patients without and with PRT. The most common recurrence regions were staion1 and station 2-4 (30.0 vs. 36.5% and 37.2% vs. 23.1%, respectively, for patients without and with PRT). The lymphatic recurrence of upper TEC was almost in station1 and station 2-4 (infield). The middle and lower TEC also had a high probability of lymphatic recurrence in station 1 and station 2-4 (totally 76.3 vs. 57.6% and 61.9 vs. 61.1%, respectively). The recurrence ratio significantly decreased in station 2-4 (infield) for middle TEC patients with PRT compared with patients without PRT (P=0.03), while no significant differences in the lymphatic recurrence ratios were observed in other regions (P>0.05). The differences of recurrence ratios in station 7, station 8 and celiac regions (infield) for lower TEC patients without and with PRT also demonstrated no statistical significance (P>0.05). The results of the present study indicated that the lower neck, supraclavicular regions and upper mediastinal regions (station 1, 2 and 4) should be included in the clinic target volume (CTV) for PRT, while lower mediastinal regions, celiac regions and anastomotic may not be included in CTV.


Characterization of catecholamine binding sites in the rat brain.
A systematic study of the effect of neurotoxic agents upon neurotransmitter binding to specific receptors requires the simultaneous assay of several closely related ligand-receptor interactions. Conditions are presented which allow the determination of dopaminergic, alpha-noradrenergic and beta-noradrenergic receptor sites within the same brain areas without major overlap of selectivity. As a result, regional distribution of catecholaminergic receptor sites and some characteristics of such binding are described.


Sexual imagery in cigarette advertising before and after the master settlement agreement.
This study examines how the sexual imagery in cigarette magazine advertisements changed as a result of the 1998 Master Settlement Agreement (MSA). After conducting a content analysis of 657 unduplicated cigarette ads from 1994 to 2003, our results revealed that cigarette advertisements featuring suggestive/partially clad female models increased significantly from the pre-MSA period (16.0%) to the post-MSA period (24.9%). In addition, we provide empirical evidence that there was an overall increase in sexually explicit cigarette advertising after the MSA. Several implications for policymakers are discussed in detail.


[Cholecystobiliary fistula: laparoscopic treatment with an endostapler].
The Authors report a case of cholecystobiliary fistula due to cholelithiasis and bile duct lithiasis, treated laparoscopically with an endostapler. In view of the rarity of this condition, we believe it may be useful to discuss the diagnostic work-up in the light of the diagnostic and therapeutic measures currently available. We also review the literature with a view to defining the existing classifications of cholecystobiliary fistulas. We conclude by stressing the importance the endoscopic placement of nasobiliary catheters preoperatively to facilitate laparoscopic treatment.


Berberine formate-succinic acid (1/1).
The title compound [systematic name: 9,10-dimethoxy-2,3-methylenedioxy-5,6-dihydrodibenzo[a,g]quinolizinium formate-succinic acid (1/1)], C(20)H(18)NO(4)(+).CHO(2)(-).C(4)H(6)O(4), contains centrosymmetric pairs of almost planar berberine cations, and hydrogen-bonded (C(4)H(6)O(4).HCOO(-))(2) rings of succinic acid with formate anions, bonded by O-H...O hydrogen bonds with O...O distances of 2.4886 (15) and 2.5652 (16) A. Pairs of cations and molecules of succinic acid are connected by non-conventional weak C-H.O hydrogen bonds, with C...O distances of 3.082 (2) and 3.178 (2) A.


Close proximity between residue 30 of phospholamban and cysteine 318 of the cardiac Ca2+ pump revealed by intermolecular thiol cross-linking.
Phospholamban (PLB) is a 52-amino acid inhibitor of the Ca(2+)-ATPase in cardiac sarcoplasmic reticulum (SERCA2a), which acts by decreasing the apparent affinity of the enzyme for Ca(2+). To localize binding sites of SERCA2a for PLB, we performed Cys-scanning mutagenesis of PLB, co-expressed the PLB mutants with SERCA2a in insect cell microsomes, and tested for cross-linking of the mutated PLB molecules to SERCA2a using 1,6-bismaleimidohexane, a 10-A-long, homobifunctional thiol cross-linking agent. Of several mutants tested, only PLB with a Cys replacement at position 30 (N30C-PLB) cross-linked to SERCA2a. Cross-linking occurred specifically and with high efficiency. The process was abolished by micromolar Ca(2+) or by an anti-PLB monoclonal antibody and was inhibited 50% by phosphorylation of PLB by cAMP-dependent protein kinase. The SERCA2a inhibitors thapsigargin and cyclopiazonic acid also completely prevented cross-linking. The two essential requirements for cross-linking of N30C-PLB to SERCA2a were a Ca(2+)-free enzyme and, unexpectedly, a micromolar concentration of ATP or ADP, demonstrating that N30C-PLB cross-links preferentially to the nucleotide-bound, E2 state of SERCA2a. Sequencing of a purified proteolytic fragment in combination with SERCA2a mutagenesis identified Cys(318) of SERCA2a as the sole amino acid cross-linked to N30C-PLB. The proximity of residue 30 of PLB to Cys(318) of SERCA2a suggests that PLB may interfere with Ca(2+) activation of SERCA2a by a protein interaction occurring near transmembrane helix M4.


Involvement of ABA- and H2O2-dependent cytosolic glucose-6-phosphate dehydrogenase in maintaining redox homeostasis in soybean roots under drought stress.
The roles of abscisic acid (ABA) and hydrogen peroxide (H2O2) in inducing glucose-6-phosphate dehydrogenase (G6PDH, EC 22.214.171.124) activity and the possible roles of G6PDH in regulating ascorbate-glutathione (AsA-GSH) cycle were investigated in soybean (Glycine max L.) roots under drought stress. Drought caused a marked increase of the total and cytosolic G6PDH activities and triggered a rapid ABA and H2O2 accumulation in soybean roots. Exogenous ABA or H2O2 treatment elevated the total and cytosolic G6PDH activities, whereas suppressing ABA or H2O2 production inhibited the drought-induced increase in total and cytosolic G6PDH activities, suggesting that ABA and H2O2 are required for drought-induced increase of total G6PDH activity, namely cytosolic G6PDH activity. Furthermore, ABA induced H2O2 production by stimulating NADPH oxidase activity under drought stress. Moreover, drought significantly increased the contents of AsA and GSH and the activities of key enzymes in AsA-GSH cycle, while application of G6PDH inhibitor to seedlings significantly reduced the above effect induced by drought. Taken together, these results indicate that H2O2 acting as a downstream signaling molecule of ABA mediates drought-induced increase in cytosolic G6PDH activity, and that enhanced cytosolic G6PDH activity maintains cellular redox homeostasis by regulating AsA-GSH cycle in soybean roots.


Videogames and guns in adolescents: T ests of a bipartite theory.
The possible role of video gaming in imprinting aggressive and specifically gun-related behaviors has been elusive, and findings regarding these associations have been inconsistent. I address this gap by proposing and testing a bipartite theory that can explain inconsistent results regarding the previously assumed linear association between videogames and gun-related behaviors. The theory suggests that this association follows a U-shape. It posits that at low levels of video gaming time, video gaming displaces gun-related behaviors and shelters adolescents by keeping them occupied and by reducing opportunities and motivation to acquire guns. However, at some level of gaming time (because most popular games adolescents play include violent aspects), the assumed imprinting of aggressive behaviors overpowers the positive displacement force, and this can trivialize and naturalize gun-carrying behaviors, and ultimately increase motivation to obtain and carry guns. I tested this theory with two national samples of American adolescents (n1 = 24,779 and n2 = 26,543, out of which 403 and 378, respectively, reported bringing a gun to school in the last month). Multiple analyses supported the proposed U-shaped association. These findings show that the moral panic over video games is largely unsubstantiated, especially among light to moderate gamers.


Differences of the effects of testosterone propionate on the production of LH and FSH.
The effects of testosterone propionate (1 mg/day) on the synthesis and circulating levels of FSH and LH were studied in normal adult male rats. The pituitary and serum gonadotrophins were measured by double antibody radioimmunoassay. The de novo synthesis of gonadotrophins was assessed by the rate of in vitro incorporation of [3H]leucine into the immunoprecipitable FSH and LH. After 4 days of treatment with testosterone propionate the circulating LH levels dropped significantly, while FSH remained unchanged. Pituitary LH content and concentration declined significantly after 1 day, and incorporation of [3H]leucine into the immunoprecipitable LH became undetectable 4 days after initiation of treatment. Pituitary FSH content and concentration showed a significant increase after the 4th day of treatment. A slight tendency towards increased incorporation of [3H]leucine into FSH was observed throughout the treatment period, although it was statistically not significant. The data provide direct evidence for a differential effect of TP on FSH and LH production by the pituitary and show that the decrease in the pituitary and plasma levels of LH in testosterone treated rats is due to the decrease in LH synthesis.


The lipidome in major depressive disorder: Shared genetic influence for ether-phosphatidylcholines, a plasma-based phenotype related to inflammation, and disease risk.
The lipidome is rapidly garnering interest in the field of psychiatry. Recent studies have implicated lipidomic changes across numerous psychiatric disorders. In particular, there is growing evidence that the concentrations of several classes of lipids are altered in those diagnosed with MDD. However, for lipidomic abnormalities to be considered potential treatment targets for MDD (rather than secondary manifestations of the disease), a shared etiology between lipid concentrations and MDD should be demonstrated. In a sample of 567 individuals from 37 extended pedigrees (average size 13.57 people, range=3-80), we used mass spectrometry lipidomic measures to evaluate the genetic overlap between twenty-three biologically distinct lipid classes and a dimensional scale of MDD. We found that the lipid class with the largest endophenotype ranking value (ERV, a standardized parametric measure of pleiotropy) were ether-phosphodatidylcholines (alkylphosphatidylcholine, PC(O) and alkenylphosphatidylcholine, PC(P) subclasses). Furthermore, we examined the cluster structure of the twenty-five species within the top-ranked lipid class, and the relationship of those clusters with MDD. This analysis revealed that species containing arachidonic acid generally exhibited the greatest degree of genetic overlap with MDD. This study is the first to demonstrate a shared genetic etiology between MDD and ether-phosphatidylcholine species containing arachidonic acid, an omega-6 fatty acid that is a precursor to inflammatory mediators, such as prostaglandins. The study highlights the potential utility of the well-characterized linoleic/arachidonic acid inflammation pathway as a diagnostic marker and/or treatment target for MDD.


Viscosity of suspensions of yttrium oxide (Y2O3) nanopowder in ethyl alcohol.
This paper presents results from measurements of viscosity of suspensions of Yttrium Oxide Y2O3 ceramic nanopowder in ethyl alcohol. The study was conducted at the request of and in cooperation with the ICMB. This research will add important information about the formation and viscosity characteristics of suspensions of nanopowders. The behavior of nanopowder suspensions has been examined in a wide range of shear rates from 0.01 s(-1) to 2000 s(-1). Additionally, the behavior of the suspension has been studied in the temperature range from -15 degrees C to 20 degrees C. Complementary experiments have been performed by application of a Rheo-NMR at Bruker Biospin and by the use of RheoScope at ThermoFisher companies.


Pushing the limits of imagination: mental practice for learning sequences.
In 2 experiments, the efficacy of motor imagery for learning to type number sequences was examined. Adults practiced typing 4-digit numbers. Then, during subsequent training, they either typed in the same or a different location, imagined typing, merely looked at each number, or performed an irrelevant task. Repetition priming (faster responses for old relative to new numbers) was observed on an immediate test and after a 3-month delay for participants who imagined typing. Improvement across the delay in typing old and new numbers was found for the imagined and actual typing conditions but not for the other conditions. The findings suggest that imagery can be used to acquire and retain representations of sequences and to improve general typing skill.


[Effects of the stimulating point and non-point on human cerebral evoked potential and spinal cord evoked potential].
The experiments were carried out on 36 normal subjects. Pain stimulation points are at Neiguan or Hegu and pain stimulation nonpoints are nearby Neiguan or Hegu. The Record locations are at cortex and cervical vertebrae. The feature of evoked cerebral potential (ECP) and spinal cord evoked potential (ESP) by pain stimulation the points or non-points were studied. The results have been obtained. 1. Pain stimulation point ECP generally consists of wave P1, N1, P2, N2, P3, N3, P4 and N4. There is a certain amplitude and latency of each wave. 2. The elements of pain stimulation non-point ECP are Similar to point ECP in the feature. Comparing Pain stimulation Point ECP with non-point ECP, the amplitude of wave P3-N3 of stimulation point ECP increases (P < 0.05). 3. Pain stimulation Point ESP and non-point ESP consist of wave P1, N1 and P2, N3. Comparing Pain stimulation point with non-point there are no significant changes in the amplitude and the latency of ESP.


The shelf life extension of refrigerated grass carp (Ctenopharyngodon idellus) fillets by chitosan coating combined with glycerol monolaurate.
A novel chitosan-based coating solution was prepared by combining glycerol monolaurate (GML) for shelf life extension of refrigerated grass carp fillets. The control and coated fillets were analyzed periodically for physicochemical (pH, thiobarbituric acid (TBA) value, total volatile basic nitrogen (TVB-N) value, K value, and shear force), microbiological (total viable counts (TVC), psychrophilic bacteria counts (PTC), Pseudomonads and H2S-producing bacteria) and sensorial characteristics. The results showed that chitosan-GML coated samples presented better quality preservation effects than chitosan coating alone. In addition, 2% chitosan enriched with 0.3% GML showed the significant (P<0.05) effectiveness in inhibiting microbial growth, nucleotide breakdown, the formation of alkaline components and texture deterioration, and maintaining sensory acceptability among the groups. These findings confirmed that chitosan coating enriched with GML was a promising method to extend the shelf life of refrigerated fillets.


Neurochemical correlates of muricidal behavior in rats.
Surgical, pharmacological or environmental manipulation are widely employed to induce muricidal behavior in naive laboratory male rats. The genetic predisposition of an animal strain to kill mice remains, however, an important factor to obtain the muricidal reaction. Data from the pertinent literature suggest that muricidal behavior may possibly be sustained by increased dopaminergic or catecholaminergic activity in the presence of reduced serotoninergic activity. The results here presented indicate, instead, that complete abolition of brain serotoninergic control, i.e., maximal depletion of brain serotonin, is just enough per se to induce muricidal activity. Further, this chemically-induced muricidal activity goes well beyond any pre-existing strain predisposition to kill mice or not.


[Effects of cardiac glycosides on RNA content in cardio-regulating structures of the hindbrain].
In the experiments on 112 white mongrel male rats using cytophotometric investigation the authors showed that digoxin in doses 0.89 and 8.9 micrograms/g in single and repeated subcutaneous administration influences differently the level of RNA in cardio-regulating structures of the hindbrain.


Relationship of high density lipoprotein cholesterol to cholesterol metabolism in the baboon (Papio sp.).
Genetic effects on serum high density lipoprotein (HDL) cholesterol concentration and several parameters of a two-pool model of cholesterol metabolism were investigated in 79 baboons, the progeny of 6 sires. Significant differences (P less than 0.05) were observed among the sire progeny groups for HDL cholesterol (HDL-C), cholesterol production rate, cholesterol mass of pool A, and the rate constants KA and KAB. Rank correlations (rs) revealed that the sire progeny group means for HDL-C are closely correlated with those for the cholesterol mass of pool A (rs = 0.89), KA (rs = -0.78), and KAB (rs = -0.94). These strong correlations suggest that pool A, KA, and KAB are influenced to a large degree by the same genes that regulate HDL-C concentration. The strong inverse relationship (rs = -0.78) between HDL-C and KA suggests that the differences among these sire progeny groups for HDL-C are due chiefly to those metabolic processes which regulate cholesterol excretion from pool A. This conclusion is consistent with reports that HDL-C is a preferred precursor for bile acid synthesis.


Design and evaluation of a touchscreen apparatus for operant research with pigeons.
We developed a touchscreen apparatus for pigeons and conducted a series of experiments that assessed its utility for free-operant procedures. The apparatus incorporated an on-board Windows computer, an electromechanical interface, an amplified speaker, and the touchscreen. We found that merely projecting a virtual key on the screen was insufficient; too many pecks missed the key. Adding a visual target in the center of the key and providing visual feedback for on-key pecks both failed to improve response accuracy. Accuracy was improved by imposing a timeout after off-key pecks or providing a physical boundary around the key. With the physical boundary, response accuracy was comparable to that obtained with conventional plastic keys, and response acquisition via autoshaping also was comparable. Mixing the color elements of the screen's pixels produced color stimuli, but the colors did not function as pure wavelengths of light in tests of stimulus generalization. Both colors and geometric shapes functioned as discriminative stimuli in multiple schedules with variable-interval and extinction components or rich and lean fixed-ratio components. In general, our touchscreen apparatus is a viable alternative to conventional pigeon chambers and increases the experimenter's options for visual stimuli, auditory stimuli, and the number and location of response keys.


[Ovarian metastasis of a thymoma].
Report about the rare occurrence of ovarian metastases from a thymoma. Exstirpation of a lymphoepithelial thymoma was performed in a female patient at the age of twenty. 10 months afterwards a large tumour in the abdomen was the cause for a laparotomy. The situs showed a gigantic ovarian tumour (size 20 X 20 X 10 cm). The histological diagnosis was a metastatic tumour from the lymphoepithelial thymoma. Salpingo-Oophorectomy, radiotherapy and immunosuppressive therapy with glucocorticoids were used.


The European core curriculum for radiotherapy technologists.
The Radiotherapy Technologist is the third member of the team responsible for the accurate delivery of radiotherapy to the cancer patient. Educational standards have been established for both radiotherapists and medical physicists and our group recognised the need to also standardise the education of radiotherapy technologists. The project commenced in 1990 and was completed by 1994 when an agreed core curriculum was presented at a consensus conference. All aspects of curriculum development and education delivery were reviewed during this four year period. Core topics were identified. educational entry standards described and a duration of three years, consistent with European Union mobility regulations, agreed. The core curriculum describes the standard necessary to be achieved for entry into the profession to ensure the optimum treatment is offered to all patients throughout the European Union. Regular review of the core curriculum should be carried out to ensure the defined standards are maintained.


One hour electrical stimulation accelerates functional recovery after femoral nerve repair.
The clinical outcome of peripheral nerve injuries requiring surgical repair is usually poor and efficient therapies do not exist. Recent work has suggested that low-frequency electrical stimulation of the severed nerve which produces repeated discharges of the parent motoneuron perikarya positively influences axonal regeneration, even if applied once for a period of only 1 h. Here we provide the first evidence for locomotor functional benefits of such stimulation. We transected the femoral nerve of adult C57BL/6J mice proximal to the bifurcation of the quadriceps and saphenous branches and electrically stimulated the proximal nerve stump for 1 h at 20-Hz frequency prior to nerve repair with a silicone cuff. Three months later, the ability of the quadriceps muscle to extend the knee in sham-stimulated mice had recovered to 63% of the preoperative values as estimated by single-frame motion analysis. After electrical stimulation, the outcome was only slightly better (73%) but the rate of functional recovery was considerably accelerated. Near-maximum recovery was achieved 6 weeks earlier than in the control group. The beneficial effects were associated with larger motoneuron cell bodies and increased diameters of regenerated axons in the quadriceps nerve branch, but not with enhanced preferential reinnervation by motoneurons of muscle as opposed to skin. The observed acceleration of functional restoration and the positive effects on motoneurons and regenerated axons indicate the potential of a clinically feasible approach for improvement of nerve repair outcome in human patients in which delayed target reinnervation is a factor limiting recovery.


The physician as fortune teller: a commentary on "The ethical justification for minimal paternalism.
...I shall summarize my argument to this point. 1) A new technology -- medicalizing life choices -- introduces additional sources of uncertainty into the physician-patient relationship. The implications for the authority-autonomy tension of that relationship are not fully worked out, as is evidenced by differing views on professional obligations. 2) The warrants for paternalism are complex, ranging from a pragmatic response in the face of uncertainty to a proactive, highly directive determination of the patient's best interests. 3) Although some proponents of autonomy argue that it entails positive rights to intervention and information, the "strong sense" of autonomy is not the prevailing view. 4) The as yet unclear benefits of knowledge about one's genetic makeup are even less clear in the case of HD. Strong circumstantial evidence of risks of harm from disclosure of unfavorable test results have not been dispelled by early experience with use of the HD test. 5) A cautious approach in the use of HD test seems warranted, even at the cost of restricting autonomy. Legitimating that approach by reference to traditional ethical theory is a necessary element in the transfer of the new technology to the wider clinical setting. 6) While PMP [the principle of minimal paternalism] attempts to offer such an approach, some questions do not appear to have been resolved or fully addressed by this formulation.


Descriptive Epidemiology of Sitting Time in Omani Men and Women: A Known Risk Factor for Non-Communicable Diseases.
Sedentary behaviors (too much sitting as distinct from too little exercise) are associated with increased risk of non-communicable diseases. Identifying the prevalence and sociodemographic correlates of sitting time can inform public health policy and prevention strategies. A population-based national survey was carried out among Omani adults in 2008 (n = 2 977) using the Global Physical Activity Questionnaire, which included a measure of total sitting time. Bivariate and regression analyses examined the associations of total sitting time with sociodemographic correlates (gender, age, education, work status, marital status, place of residence, and wealth). The proportion who sat for ≥ 7 hours/day was significantly higher in older than in younger adults (men: 22.0% vs. 14.6%, p < 0.010; women: 26.9% vs. 15.2%, p < 0.001, respectively). The odds ratio (OR) for prolonged sitting was half for men who were not working compared to those who were (p < 0.050). For younger women, the OR for sitting ≥ 7 hours/day was nearly a third for educated women compared to least educated (p = 0.035). For older women, the OR for prolonged sitting was more than double for married women compared to unmarried (p < 0.001). One in five Omani adults was identified as sitting for prolonged periods, at levels understood to have deleterious health consequences. Higher-risk groups include older adults and working men. With sitting time identified as a key behavioral risk to be targeted for the prevention of non-communicable diseases, further research is needed to understand the factors associated with domain-specific sitting time in order to guide prevention programs and broader public health approaches.


[Study of single cell PCR for HLA typing].
To apply the single cell nested multiplex polymerase chain reaction (PCR) to HLA typing, and analyze the influence factors on the amplification results. Single cell DNA templates were prepared with different methods. The exon 2, 3 and intron 2 of HLA-A, B, and exon 2 of DRBI were amplified using multiplex PCR. The second round of SSP-PCR HLA typing was carried out according to the large scale routine HLA typing results. Enzyme lysis method was the most efficient procedure for preparing the single cell DNA template, with a success rate (SR) of 93.3%, while the SRs of alkali lysis and freezing-thaw lysis methods were 83.3% and 73.3%, respectively. The second round amplification using enzyme lysis and SSP-PCR in 20 samples obtained a 95% success rate and a 15% allele drop out rate. The time for performing the whole procedure was less than 6 hours. The modified nested multiplex PCR technique is efficient for single cell HLA typing and might be applied to clinical preimplantation genetic diagnosis.


Perceived Neighborhood Environment Impacts on Health Behavior, Multi-Dimensional Health, and Life Satisfaction.
The impacts of perceived neighborhood environment on adults' health and life satisfaction have drawn increasing academic attention. However, previous studies usually examine multi-dimensional (physical, mental, and perceived) health and life satisfaction separately, and few studies dealt with them simultaneously. Moreover, limited research revealed the mechanisms behind the effects of perceived neighborhood environment on health and life satisfaction, as well as how such effects are moderated by socio-demographics. Therefore, employing the 2016 China Family Panel Study Dataset and using structural equation modeling, this study delves into the complicated relationships among perceived neighborhood environment, health behavior, health outcomes (i.e., body mass index, self-rated health status, and depression), and life satisfaction. Notably, it considers mediation and moderation simultaneously. It finds: (1) Better perceived neighborhood environment significantly promotes physical activity and reduces sedentary behavior, smoking, and drinking; (2) Health behavior fully mediates the effects of perceived neighborhood environment on health; (3) Perceived neighborhood environment significantly affects life satisfaction both directly and indirectly (through health behavior and health outcomes); (4) Socio-demographics moderate the above relationships. This study disentangles the complicated impacts of perceived neighborhood environment on adults' multi-dimensional health and life satisfaction, thus providing policy makers and practitioners with nuanced knowledge for intervention.


Programmable i-motif DNA folding topology for a pH-switched reversible molecular sensing device.
Four-stranded DNAs including G-quadruplexes and i-motifs are formed from four stretches of identical bases (G or C). A challenge remains in controlling the intermolecular folding of different G-rich or C-rich strands due to the self-association of each component. Here, we introduce a well-designed bimolecular i-motif that does not allow the dimerization of the same strand, and illustrate its usefulness in a pH-switched ATP-sensing DNA molecular device. We analyze two groups of i-motif DNAs containing two stretches of different C-residues (Cn-1TmCn and CnTmCn-1; n = 3-6, m = 1, 3) and show that their bimolecular folding patterns (L- and H-form) noticeably differs in the thermal stability. The L-form structures generally display a relatively low stability, with a bigger difference from that of conventional i-motifs formed by CnTmCn. It inspires us to at utmost improving the structural stability by extending the core of L-form bimolecular i-motifs with a few flanking noncanonical base pairs, and therefore to avoid the dimeric association of each component. This meaningful bimolecular i-motif is then incorporated into a three-way junction (3WJ) and a four-way junction (4WJ) functionalized with two components of a ATP-binding split DNA aptamer, allowing the pH-triggered directional assembly of 3WJ and 4WJ into the desired (3+4)WJ structure that is verified by gel electrophoresis. It therefore enables the ATP-induced association of the split aptamer within the (3+4)WJ structure, as monitored by fluorescence quenching. In this way, the designed DNA system behaves as a pH-switched reversible molecular device, showing a high sensitivity and selectivity for fluorescent ATP analysis. The i-motif folding topology-programmed DNA nanoassembly may find more applications in the context of larger 2D/3D DNA nanostructures like lattices and polyhedra.


Full-endoscopic foraminoplasty for highly down-migrated lumbar disc herniation.
Multiple surgical approaches have been studied and accepted for the removal of highly downward migrated lumbar disc herniation (LDH). Here, we investigated the efficacy and safety of full-endoscopic foraminoplasty for highly downward migrated LDH. Thirty-seven patients with highly down-migrated LDH treated by the full-endoscopic foraminoplasty between January 2018 and January 2020 were retrospectively investigated. Clinical parameters were evaluated preoperatively and 1, 6, and 12 months postoperatively, using pre- and post-operative Oswestry Disability Index (ODI) scores for functional improvement, visual analog scale (VAS) for leg and back pain, and modified MacNab criteria for patients satisfactory. Thirty-seven patients with highly downward migrated LDH were successfully removed via the transforaminal full-endoscopic discectomy. The average VAS back and leg pain scores were significantly reduced from 7.41 ± 1.17 and 8.68 ± 1.06 before operation to 3.14 ± 0.89 and 2.70 ± 0.46 at postoperative 1 month, and 1.76 ± 0.59 and 0.92 ± 0.28 at postoperative 12 months, respectively (P < 0.05). The average ODI scores were reduced from 92.86 ± 6.41 to 15.30 ± 4.43 at postoperative 1 month, and 9.81 ± 3.24 at postoperative 12 months (P < 0.05). Based on the modifed MacNab criteria, 36 out of 37 patients (97.30%) were rated as excellent or good outcomes. The full-endoscopic foraminoplasty can be used successfully for surgical removal of high grade down-migrated LDH, and it could serve as an efficient alternative technique for patients with highly downward migrated LDH.


Targeting an allosteric site in dynamin-related protein 1 to inhibit Fis1-mediated mitochondrial dysfunction.
The large cytosolic GTPase, dynamin-related protein 1 (Drp1), mediates both physiological and pathological mitochondrial fission. Cell stress triggers Drp1 binding to mitochondrial Fis1 and subsequently, mitochondrial fragmentation, ROS production, metabolic collapse, and cell death. Because Drp1 also mediates physiological fission by binding to mitochondrial Mff, therapeutics that inhibit pathological fission should spare physiological mitochondrial fission. P110, a peptide inhibitor of Drp1-Fis1 interaction, reduces pathology in numerous models of neurodegeneration, ischemia, and sepsis without blocking the physiological functions of Drp1. Since peptides have pharmacokinetic limitations, we set out to identify small molecules that mimic P110's benefit. We map the P110-binding site to a switch I-adjacent grove (SWAG) on Drp1. Screening for SWAG-binding small molecules identifies SC9, which mimics P110's benefits in cells and a mouse model of endotoxemia. We suggest that the SWAG-binding small molecules discovered in this study may reduce the burden of Drp1-mediated pathologies and potentially pathologies associated with other members of the GTPase family.


One-step hot formamide extraction of RNA from Saccharomyces cerevisiae.
Current methods for isolating RNA from budding yeast require lengthy and laborious steps such as freezing and heating with phenol, homogenization with glass beads, or enzymatic digestion of the cell wall. Here, extraction with a solution of formamide and EDTA was adapted to isolate RNA from whole yeast cells through a rapid and easily scalable procedure that does not require mechanical cell lysis, phenol, or enzymes. RNA extracted with formamide-EDTA can be directly loaded on gels for electrophoretic analysis without alcohol precipitation. A simplified protocol for downstream DNase treatment and reverse transcription reaction is also included. The formamide-EDTA extraction of yeast RNA is faster, safer, and more economical than conventional methods, outperforms them in terms of total yield, and greatly increases throughput.


New Hypoxylon species and notes on some names associated with or related to Hypoxylon.
These new species of Hypoxylon are described: H. elevatidiscus, H. squamulosum, H. subalbum and H. vinosopulvinatum. A referenced list of all Hypoxylon species known to us described since 1996 is given and a key presented. Names associated with Hypoxylon that were not given in the Ju and Rogers monograph are annotated and diagnostic corrections of taxa discussed in that monograph are given.


Cesarean delivery rates, hospital readiness and quality of clinical management in Ethiopia: national results from two cross-sectional emergency obstetric and newborn care assessments.
Cesarean delivery (CD) rates have reached epidemic levels in many high and middle income countries while increasingly, low income countries are challenged both by high urban CD rates and high unmet need in rural areas. The managing authority of health care institutions often plays a role in these disparities. This paper shows changes between 2008 and 2016 in Ethiopian CD rates, readiness of hospitals to provide CD and quality of clinical care, while highlighting the role of hospital management authority. This secondary data analysis draws from two national cross-sectional studies to assess emergency obstetric and newborn care. The sample includes 111 hospitals in 2008 and 316 hospitals in 2016, and 275 women whose CD chart was reviewed in 2008 and 568 in 2016. Descriptive statistics are used to describe our primary outcome measures: population- and institutional-based CD rates; hospital readiness to perform CD; quality of clinical management, including the relative size of Robson classification groups. The national population CD rate increased from 2008 to 2016 (< 1 to 2.7%) as did all regional rates. Rates in 2016 ranged from 24% in urban settings to less than 1% in several rural regions. The institutional rate was 54% in private for-profit hospitals in 2016, up from 46% in 2008. Hospital readiness to perform CDs increased in public and private for-profit hospitals. Only half of the women whose charts were reviewed received uterotonics after delivery of the baby, but use of prophylactic antibiotics was high. Partograph use increased from 9 to 42% in public hospitals, but was negligible or declined elsewhere. In 2016, 40% of chart reviews from public hospitals were among low-risk nulliparous women (Robson groups 1&2). Between 2008 and 2016, government increased the availability of CD services, improved public hospital readiness and some aspects of clinical quality. Strategies tailored to further reduce the high unmet need for CD and what appears to be an increasing number of unnecessary cesareans are discussed. Adherence to best practices and universal coverage of water and electricity will improve the quality of hospital services while the use of the Robson classification system may serve as a useful quality improvement tool.


Juvenile myoclonic epilepsy starting in the eighth decade.
Juvenile myoclonic epilepsy (JME) typically begins at age 10-17 years. We present two patients, with no previous history of epileptic seizures, in whom JME began after the age of 70. The clinical picture of these patients did not differ from "typical" JME except for the patient's age and age at epilepsy-onset. We suggest that not only symptomatic epilepsy, but also some idiopathic epilepsies, can begin or can be reactivated in elderly people. This may be more evidence that susceptibility to epileptic seizures is increased after 60 years of age.


Development of nitric oxide catalytic coatings by conjugating 3,3-disulfodipropionic acid and 3,3-diselenodipropionic acid for improving hemocompatibility.
Nitric oxide (NO), discovered as an endothelium-derived relaxing factor, has been found to have multiple intracellular effects in vascular diseases including vasorelaxation regulation, endothelial regeneration, inhibition of leukocyte chemotaxis, and platelet activation. In the work described here, the authors have developed a NO-catalytic bioactive coating for improving hemocompatibility. The authors first prepared a dopamine and hexamethylendiamine (PDAM/HD) amine-rich adherent copolymer coating to introduce amine groups onto 316L stainless steel, followed by covalently conjugating 3,3-disulfodipropionic acid (S-S) and 3,3-diselenodipropionic acid (Se-Se), which mimic glutathione peroxidase-like catalytic production of NO. S-S and Se-Se were immobilized on the PDAM/HD surface via carbodiimide coupling chemistry. X-ray photoelectron spectroscopy analysis revealed clear S2p and Se3d signals, confirming the immobilization of S-S and Se-Se on the PDAM/HD surface. The NO release behavior of different samples was investigated. In detail, two species of thionitrites (RSNO), S-nitrosoglutathione (GSNO, endogenous NO donors) and S-nitrosoacetylpenicillamine (SNAP) were chosen as NO donors to investigate the NO catalytic properties of S-S and Se-Se modified PDAM/HD surfaces. Not only Se-Se@PDAM/HD but also S-S@PDAM/HD coatings showed the ability to continuously catalyze RSNO to generate NO in the presence of proper thiol reducing agent. For the Se-Se@PDAM/HD coating, the NO release amount and rate were greater than S-S@PDAM/HD in both GSNO and SNAP conditions. The results showed that organosulfide species possesses NO catalytic ability as well as organoselenium species. The authors demonstrated that both S-S@PDAM/HD and Se-Se@PDAM/HD coatings exhibited outstanding inhibition effect on platelet adhesion, aggregation and activation via the cyclic guanylate monophosphate signal pathway. Thus these results suggested that NO catalytic coatings based on organoselenium and organosulfide species immobilization can help to improve hemocompatibility. NO-catalytic strategies possess huge potential applications in blood-contacting devices.


Quality-of-Life and Economic Outcomes of Assessing Fractional Flow Reserve With Computed Tomography Angiography: PLATFORM.
Fractional flow reserve estimated using computed tomography (FFRCT) might improve evaluation of patients with chest pain. The authors sought to determine the effect on cost and quality of life (QOL) of using FFRCT instead of usual care to evaluate stable patients with symptoms suspicious for coronary disease. Symptomatic patients without known coronary disease were enrolled into 2 strata based on whether invasive or noninvasive diagnostic testing was planned. In each stratum, consecutive observational cohorts were evaluated with either usual care or FFRCT. The number of diagnostic tests, invasive procedures, hospitalizations, and medications during 90-day follow-up were multiplied by U.S. cost weights and summed to derive total medical costs. Changes in QOL from baseline to 90 days were assessed using the Seattle Angina Questionnaire, the EuroQOL, and a visual analog scale. In the 584 patients, 74% had atypical angina, and the pre-test probability of coronary disease was 49%. In the planned invasive stratum, mean costs were 32% lower among the FFRCT patients than among the usual care patients ($7,343 vs. $10,734 p < 0.0001). In the noninvasive stratum, mean costs were not significantly different between the FFRCT patients and the usual care patients ($2,679 vs. $2,137; p = 0.26). In a sensitivity analysis, when the cost weight of FFRCT was set to 7 times that of computed tomography angiography, the FFRCT group still had lower costs than the usual care group in the invasive testing stratum ($8,619 vs. $ 10,734; p < 0.0001), whereas in the noninvasive testing stratum, when the cost weight of FFRCT was set to one-half that of computed tomography angiography, the FFRCT group had higher costs than the usual care group ($2,766 vs. $2,137; p = 0.02). Each QOL score improved in the overall study population (p < 0.0001). In the noninvasive stratum, QOL scores improved more in FFRCT patients than in usual care patients: Seattle Angina Questionnaire 19.5 versus 11.4, p = 0.003; EuroQOL 0.08 versus 0.03, p = 0.002; and visual analog scale 4.1 versus 2.3, p = 0.82. In the invasive cohort, the improvements in QOL were similar in the FFRCT and usual care patients. An evaluation strategy based on FFRCT was associated with less resource use and lower costs within 90 days than evaluation with invasive coronary angiography. Evaluation with FFRCT was associated with greater improvement in quality of life than evaluation with usual noninvasive testing. (Prospective Longitudinal Trial of FFRCT: Outcomes and Resource Impacts [PLATFORM]; NCT01943903).