Selective detection of luminescence from semiconductor quantum dots by nanosecond time-gated imaging with a colour-masked CCD detector.
Quantum dots are of considerable interest as highly detectable labels with broad absorption, narrow spectral emission and good quantum yields. The luminescence emission has a longer decay time than that of the most common fluorophores, leading to facile rejection of much background emission (such as autofluorescence from biological samples) by means of gated detection. Here, it is shown that a new technique, true-colour nanosecond time-gated luminescence imaging, can be used for selective detection of quantum dot luminescence and should prove valuable for multiplexed detection on the basis of both spectral emission profile and luminescence decay time.


Racial disparities in time to laparoscopic cholecystectomy for acute cholecystitis.
Disparities in healthcare exist, yet few data are available on racial differences in time from admission to surgery. This study aimed to compare time from admission to laparoscopic cholecystectomy for acute cholecystitis between non-Hispanic Black and non-Hispanic White patients. Patients who underwent laparoscopic cholecystectomy for acute cholecystitis from 2010 to 2020 were identified using NSQIP. Time to surgery and additional preoperative, operative, and postoperative variables were analyzed. In the univariate analysis, 19.4% of Black patients experienced a time to surgery >1 day compared with 13.4% of White patients (p < 0.0001). In the multivariable analysis, controlling for potential confounding factors, Black patients were found to be more likely than White patients to experience a time to surgery >1 day (OR 1.23, 95% CI 1.17-1.30, p < 0.0001). Further investigation is indicated to better define the nature and significance of gender, race, and other biases in surgical care. Surgeons should be aware that biases may adversely impact patient care and should strive to identify and proactively address them to promote health equity in surgery.


Infraslow closed-loop brain training for anxiety and depression (ISAD): a protocol for a randomized, double-blind, sham-controlled pilot trial in adult females with internalizing disorders.
The core intrinsic connectivity networks (core-ICNs), encompassing the default-mode network (DMN), salience network (SN) and central executive network (CEN), have been shown to be dysfunctional in individuals with internalizing disorders (IDs, e.g. major depressive disorder, MDD; generalized anxiety disorder, GAD; social anxiety disorder, SOC). As such, source-localized, closed-loop brain training of electrophysiological signals, also known as standardized low-resolution electromagnetic tomography (sLORETA) neurofeedback (NFB), targeting key cortical nodes within these networks has the potential to reduce symptoms associated with IDs and restore normal core ICN function. We intend to conduct a randomized, double-blind (participant and assessor), sham-controlled, parallel-group (3-arm) trial of sLORETA infraslow (<0.1 Hz) fluctuation neurofeedback (sLORETA ISF-NFB) 3 times per week over 4 weeks in participants (n=60) with IDs. Our primary objectives will be to examine patient-reported outcomes (PROs) and neurophysiological measures to (1) compare the potential effects of sham ISF-NFB to either genuine 1-region ISF-NFB or genuine 2-region ISF-NFB, and (2) assess for potential associations between changes in PRO scores and modifications of electroencephalographic (EEG) activity/connectivity within/between the trained regions of interest (ROIs). As part of an exploratory analysis, we will investigate the effects of additional training sessions and the potential for the potentiation of the effects over time. We will randomly assign participants who meet the criteria for MDD, GAD, and/or SOC per the MINI (Mini International Neuropsychiatric Interview for DSM-5) to one of three groups: (1) 12 sessions of posterior cingulate cortex (PCC) ISF-NFB up-training (n=15), (2) 12 sessions of concurrent PCC ISF up-training and dorsal anterior cingulate cortex (dACC) ISF-NFB down-training (n=15), or (3) 6 sessions of yoked-sham training followed by 6 sessions genuine ISF-NFB (n=30). Transdiagnostic PROs (Hospital Anxiety and Depression Scale, HADS; Inventory of Depression and Anxiety Symptoms - Second Version, IDAS-II; Multidimensional Emotional Disorder Inventory, MEDI; Intolerance of Uncertainty Scale - Short Form, IUS-12; Repetitive Thinking Questionnaire, RTQ-10) as well as resting-state neurophysiological measures (full-band EEG and ECG) will be collected from all subjects during two baseline sessions (approximately 1 week apart) then at post 6 sessions, post 12 sessions, and follow-up (1 month later). We will employ Bayesian methods in R and advanced source-localisation software (i.e. exact low-resolution brain electromagnetic tomography; eLORETA) in our analysis. This protocol will outline the rationale and research methodology for a clinical pilot trial of sLORETA ISF-NFB targeting key nodes within the core-ICNs in a female ID population with the primary aims being to assess its potential efficacy via transdiagnostic PROs and relevant neurophysiological measures. Our study was prospectively registered with the Australia New Zealand Clinical Trials Registry (ANZCTR; Trial ID: ACTRN12619001428156). Registered on October 15, 2019.


Systematic review about etiologic association to the leukoerythroblastic reaction.
Leukoerythroblastic reaction (LER) is characterized by the presence of immature erythroid cells and myeloid precursors (metamyelocytes, myelocytes, promyelocytes, myeloblasts, and blasts) as well as, exclusively in myelofibrotic disorders, teardrop cells in the peripheral blood (J Pathol Bacteriol, 42, 1936, 541; Semaine Med, 22, 1902, 373). Research on how to interpret LER and its meaning in clinical practice is scarce, and there is no consensus on the diagnostic criteria. We summarize the current evidence with the aim of clarifying the knowledge on this subject. We conducted a comprehensive search of the PubMed-MEDLINE, EMBASE and ELSEVIER databases, the Cochrane Library, Google Scholar, and medical journals to identify relevant papers. Our search identified 425 papers, of which, 35 (11 trials and 24 case reports) ultimately met the inclusion criteria. These showed two principal groups of diseases associated with leukoerythroblastosis (LEB), corresponding to solid and hematological malignancies. The other etiologies, in order of frequency, were hemolytic diseases, infection, and others, while hemorrhage was only reported in the trials group. The literature on LER is scarce and heterogeneous. The etiological factors of LER are diverse, and its presence in malignant disease is an indicator of disease progression and an adverse prognosis suggesting poor survival. In those cases where LER had neither hematological nor solid neoplasms, its manifestation, prognosis and its impact on our daily clinical practice are unknown.


A self-administered semiquantitative food-frequency questionnaire with optical reading and its concurrent validation.
An improved semiquantitative self-administered food frequency questionnaire has been designed in order to investigate possible associations between diet and health, to plan nutrition education programmes, and to examine dietary compliance. The questionnaire consists of 16 printed forms and 16 pages with coloured photos of the most common foods and courses from the Italian diet. Instructions and other questions are included. The questionnaire uses optical reading from a scanner connected to a personal computer. The questionnaire was validated by comparing it with the seven-day weighed record method using 46 healthy adult volunteers. Significant correlations were found for all nutrients tested (Spearman rank correlation procedure), r ranging from 0.33 for ascorbic acid to 0.84 for alcohol. The two methods gave comparable results (Wilcoxon matched-pairs signed rank test) for all nutrients except riboflavin and alcohol. Similarity of the two methods in classifying relative intakes was examined by determining the frequency of similar classification into tertiles. Half of the subjects were correctly classified for most nutrients and for frequency of consumption of 18 food groups.


MicroRNA let-7b inhibits keratinocyte differentiation by targeting IL-6 mediated ERK signaling in psoriasis.
The extensive involvement of microRNA (miRNA) in the pathophysiology of psoriasis is well documented. However, in order for this information to be useful in therapeutic manipulation of miRNA levels, it is essential that detailed functional mechanisms are elucidated. This study aimed to explore the effects of IL-6 targeting by let-7b and ERK1/2 mediated signaling on keratinocyte differentiation in psoriasis. Following imiquimod cream (IMQ) application to let-7bTG (keratinocyte-specific let-7b overexpression mouse) and control mice for 7 days, we analyzed erythema, scaling and thickening of skin. A dual luciferase reporter assay and bioinformatics was carried out to detect target gene of let-7b. Additionally, the differentiation markers were measured. Immunohistochemistry analyses demonstrate a relationship of let-7b with IL-6 and ERK signaling. we found let-7bTG inhibits acanthosis and reduces the disease severity by treatment with IMQ compared to wild-type mice. Further study illustrated that let-7b promotes differentiation of keratinocytes in vivo and in vitro. Using bioinformatics and reporter gene assays, we found that IL-6 is a target gene of let-7b. In psoriasis, high expression levels of IL-6 lead to increased acivation of p-ERK1/2. High levels of let-7bTG transgene expression suppresses IL-6 expression and leads to increased keratinocyte differentiation. Moreover, let-7b acts as an upstream negative regulator of the ERK signaling pathway in keratinocytes of psoriasis. Our result reveals a previously unknown mechanism for regulation of IL-6 levels during psoriasis by let-7b and highlights a critical role for the ERK1/2 signaling pathway in epidermal differentiation during psoriasis. The ethical approval for this study was from the Affiliated Hospital of Medical University of Anhui _ Fast_ PJ2017-11-14.


A case of primary racemose hemangioma with endobronchial lesions demonstrating recurrent hemoptysis initially treated with bronchial arterial embolization.
Primary racemose hemangioma of the bronchial artery (RHBA) is one of the causes of massive hemoptysis. A 72-year-old woman was admitted to our hospital with recurrent hemoptysis. Bronchoscopy showed an endobronchial lesion, and the angiography of the right bronchial arteries indicated RHBA. Bronchial arterial embolization (BAE) was performed to prevent hemoptysis. Although the endobronchial lesion shrank after the first BAE, the lesion re-increased and caused massive hemoptysis. A thoracoscopic right upper lobectomy was performed, and hemoptysis did not recur. Therefore, in cases of RHBA where there is recurrent hemoptysis and the endobronchial lesions that remain after BAE, additional treatments should be considered.


5,6-Dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) induces apoptosis in breast cancer cells through inhibiting of Mcl-1 expression.
The effective treatment of breast cancer remains a profound clinical challenge, especially due to drug resistance and metastasis which unfortunately arise in many patients. The transcription inhibitor 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole (DRB), as a selective inhibitor of cyclin-dependent kinase 9, was shown to be effective in inducing apoptosis in various hematopoietic malignancies. However, the anticancer efficacy of DRB against breast cancer is still unclear. Herein, we demonstrated that administration of DRB to the breast cancer cell line led to the inhibition of cellular proliferation and induction of the typical signs of apoptotic cells, including the increases in Annexin V-positive cells, DNA fragmentation, and activation of caspase-7, caspase-9, and poly (ADP ribose) polymerase (PARP). Treatment of DRB resulted in a rapid decline in the myeloid cell leukemia 1 (Mcl-1) protein, whereas levels of other antiapoptotic proteins did not change. Overexpression of Mcl-1 decreased the DRB-induced PARP cleavage, whereas knockdown of Mcl-1 enhanced the effects of DRB on PARP activation, indicating that loss of Mcl-1 accounts for the DRB-mediated apoptosis in MCF-7 cells, but not in T-47D. Furthermore, we found that co-treatment of MCF-7 cells with an inhibitor of AKT (LY294002) or an inhibitor of the proteasome (MG-132) significantly augmented the DRB-induced apoptosis. These data suggested that DRB in combination with LY294002 or MG-132 may have a greater therapeutic potency against breast cancer cells.


The identification of byproducts from the catalytic reduction reaction of 4-nitrophenol to 4-aminophenol: A systematic spectroscopic study.
Acetaminophenol, commonly recognized as paracetamol (considered safer than aspirin) is formed by nitration of phenol (4-nitrophenol (4-NP)) for its conversion to 4-aminophenol (4-AP), followed by the acetylation for the final product. As 4-NP is an intermediate product in acetaminophenol (paracetamol) production from phenol the dynamic analysis of acetylation of amine group is important. This study focuses on the feasibility of spectroscopic studies to monitor the removal of 4-NP using sodium borohydride (NaBH4) probe reaction in the presence of silver, gold, and bimetallic Ag/Au nanoparticles. UV-visible absorbance and fluorescence spectroscopy measurements reveal the formation of 1,4-benzoquinone (BQ), hydroquinone (HQ), and phenol (Ph) as the final products, in addition to the formation of typically reported 4-AP. The intermediates of NaBH4 seem to play a significant role in the formation of BQ, which converts to HQ in the basic medium followed by the formation of phenol in an acidic medium. Complete kinetic analysis with respect to spectroscopic studies of the standard compounds is presented. Similar results were obtained with 4-NP spiked river and seawater samples. The present findings may lead to catalytic benchmarking that can differ from most of the current practices and highlight the importance of adopting a holistic approach towards the fundamental understanding of 4-NP catalytic reduction that must take into account the concentration of NaBH4 and pH interdependencies.


Characterization of the contamination fingerprint of wastewater treatment plant effluents in the Henares River Basin (central Spain) based on target and suspect screening analysis.
The interest in contaminants of emerging concern (CECs) has increased lately due to their continued emission and potential ecotoxicological hazards. Wastewater treatment plants (WWTPs) are generally not capable of eliminating them and are considered the main pathway for CECs to the aquatic environment. The number of CECs in WWTPs effluents is often so large that complementary approaches to the conventional target analysis need to be implemented. Within this context, multitarget quantitative analysis (162 compounds) and a suspect screening (>40,000 suspects) approaches were applied to characterize the CEC fingerprint in effluents of five WWTPs in the Henares River basin (central Spain) during two sampling campaigns (summer and autumn). The results indicated that 76% of the compounds quantified corresponded to pharmaceuticals, 21% to pesticides and 3% to industrial chemicals. Apart from the 82 compounds quantified, suspect screening increased the list to 297 annotated compounds. Significant differences in the CEC fingerprint were observed between summer and autumn campaigns and between the WWTPs, being those serving the city of Alcalá de Henares the ones with the largest number of compounds and concentrations. Finally, a risk prioritization approach was applied based on risk quotients (RQs) for algae, invertebrates, and fish. Azithromycin, diuron, chlortoluron, clarithromycin, sertraline and sulfamethoxazole were identified as having the largest risks to algae. As for invertebrates, the compounds having the largest RQs were carbendazim, fenoxycarb and eprosartan, and for fish acetaminophen, DEET, carbendazim, caffeine, fluconazole, and azithromycin. The two WWTPs showing higher calculated Risk Indexes had tertiary treatments, which points towards the need of increasing the removal efficiency in urban WWTPs. Furthermore, considering the complex mixtures emitted into the environment and the low dilution capacity of Mediterranean rivers, we recommend the development of detailed monitoring plans and stricter regulations to control the chemical burden created to freshwater ecosystems.


Neonatal organ dysfunction among newborns at gestational age 34 weeks and umbilical arterial pH<7.00.
Among newborns at 34 weeks or more with umbilical arterial pH<7.00, we endeavoured to determine the pH threshold and risk factors for neonatal organ injury within 72 hours of birth. Retrospectively, all non-anomalous newborns delivered over 6 years near term with a low pH were identified. Each case of a newborn with injury was compared with the next four neonates with a pH below 7.00 and no injury. A receiver-operating characteristic (ROC) curve and unconditional logistic regression was used. Of the 87 newborns with pathologic acidosis, 16% had neonatal organ system injury. Inspection of the ROC curve indicates that a pH of 6.92 is the threshold that identifies newborns who will have damage to organs. Unconditional logistic regression analysis indicates that the significant risk factors for morbidity were an Apgar score <or=7 at 5 minutes, an UA pH <or=6.92, a sentinel event, and a history of maternal seizures among those at 37 weeks or more. Among newborns at >or=37 weeks, pH <or=6.92 is the threshold linked with neonatal organ dysfunction.


Risk Factors for Tuberculosis (TB) Among Household Contacts of Patients With Smear-Positive TB in 8 Provinces of Vietnam: A Nested Case-Control Study.
Tuberculosis (TB) continues to account for significant morbidity and mortality annually. Household contacts (HHCs) of persons with TB are a key population for targeting prevention and control interventions. We aimed to identify risk factors associated with developing TB among HHCs. We conducted a nested case-control study among HHCs in 8 provinces in Vietnam enrolled in a randomized controlled trial of active case finding for TB. Cases were any HHCs diagnosed and registered with TB within the Vietnam National TB Program during 2 years of follow-up. Controls were selected by simple random sampling from the remaining HHCs. Risk factor data were collected at enrollment and during follow-up. A logistic regression model was developed to determine predictors of TB among HHCs. We selected 1254 HHCs for the analysis: 214 cases and 1040 controls. Underlying characteristics varied between both groups; cases were older, more likely to be male, with a higher proportion of reported previous TB and diabetes. Risk factors associated with a TB diagnosis included being male (adjusted odds ratio [aOR], 1.4; 95% confidence interval [CI], 1.03-2.0), residing in an urban setting (aOR, 1.8; 1.3-2.5), prior TB (aOR, 4.6; 2.5-8.7), history of diabetes (aOR, 3.1; 1.7-5.8), current smoking (aOR, 3.1; 2.2-4.4), and prolonged history of coughing in the index case at enrollment (OR , 1.6; 1.1-2.3). Household contacts remain an important key population for TB prevention and control. TB programs should ensure effective contact investigations are implemented for household contacts, particularly those with additional risk factors for developing TB.


The SMile Card: a computerised data card for multiple sclerosis patients. SMile Card Scientific Board.
The SMile Card was developed as a means for computerising clinical information for the purpose of transferability, accessibility, standardisation and compilation of a national database of demographic and clinical information about multiple sclerosis (MS) patients. In many European countries, centres for MS are organised independently from one another making collaboration, consultation and patient referral complicated. Only the more highly advanced clinical centres, generally located in large urban areas, have had the possibility to utilise technical possibilities for improving the organisation of patient clinical and research information, although independently from other centres. The information system, developed utilising the Visual Basic language for Microsoft Windows 95, stores information via a 'smart card' in a database which is initiated and updated utilising a microprocessor, located at each neurological clinic. The SMile Card, currently being tested in Italy, permits patients to carry with them all relevant medical information without limitations. Neurologists are able to access and update, via the microprocessor, the patient's entire medical history and MS-related information, including the complete neurological examination and laboratory test results. The SMile Card provides MS patients and neurologists with a complete computerised archive of clinical information which is accessible throughout the country. In addition, data from the SMile Card system can be exported to other database programs.


Gadolinium-enhanced computed tomography cystogram to diagnose bladder augment rupture in patients with iodine sensitivity.
Anaphylactic reaction to iodinated contrast is a potentially life-threatening complication of diagnostic imaging studies. We report the successful use of gadolinium as an alternative contrast agent for computed tomography cystogram in a patient with a history of anaphylactic reaction to iodinated contrast. This technique allowed us rapidly to diagnose a rupture of her bladder augmentation and pursue operative repair.


Chemistry-intuitive explanation of graph neural networks for molecular property prediction with substructure masking.
Graph neural networks (GNNs) have been widely used in molecular property prediction, but explaining their black-box predictions is still a challenge. Most existing explanation methods for GNNs in chemistry focus on attributing model predictions to individual nodes, edges or fragments that are not necessarily derived from a chemically meaningful segmentation of molecules. To address this challenge, we propose a method named substructure mask explanation (SME). SME is based on well-established molecular segmentation methods and provides an interpretation that aligns with the understanding of chemists. We apply SME to elucidate how GNNs learn to predict aqueous solubility, genotoxicity, cardiotoxicity and blood-brain barrier permeation for small molecules. SME provides interpretation that is consistent with the understanding of chemists, alerts them to unreliable performance, and guides them in structural optimization for target properties. Hence, we believe that SME empowers chemists to confidently mine structure-activity relationship (SAR) from reliable GNNs through a transparent inspection on how GNNs pick up useful signals when learning from data.


Nerve growth factor contributes to the up-regulation of growth-associated protein 43 and preprotachykinin A messenger RNAs in primary sensory neurons following peripheral inflammation.
Peripheral inflammation induced in adult rats by an intraplantar injection of complete Freund's adjuvant results in a rapid (6 h) increase in the expression of the messenger RNAs for the neuronal growth-associated protein 43 and for preprotachykinin A, the precursor for substance P, in dorsal root ganglion sensory neurons innervating the inflamed area. This increase peaks at 48 h and then declines by five days. The changes are present in the dorsal root ganglion cells innervating the inflamed skin (lumbar 4 or 5) but no elevation was found in the third lumbar dorsal root ganglion which innervates neighbouring non-inflamed skin. The increased growth-associated protein 43 messenger RNA in the dorsal root ganglion is followed by a marked increase in growth-associated protein 43-like immunoreactive fibres in the epidermis of the inflamed skin. Systemic administration of neutralizing anti-nerve growth factor antibodies immediately prior to the inflammation prevents the increase in growth-associated protein 43 and preprotachykinin A messenger RNAs in the sensory neurons. A subcutaneous injection of nerve growth factor (200 ng) into the hindpaw elevates preprotachykinin A but not growth-associated protein 43 messenger RNA in the fourth lumbar dorsal root ganglion 48 h post-injection and this could be prevented by co-administration of the anti-nerve growth factor serum. The production of nerve growth factor in inflamed target tissues leads to alterations in the phenotype of responsive adult primary sensory neurons which include a change in the levels of a growth-related protein and a peptide neuromodulator.(ABSTRACT TRUNCATED AT 250 WORDS)


A new ferulol derivative isolated from the aerial parts of Ferulago nodosa (L.) Boiss. growing in Sicily (Italy).
Ferulago nodosa (L.) Boiss. (Apiaceae) is a species occurring in the Balkan-Tyrrhenian area being present in Crete, Greece, Albania, and probably in Macedonia. Although the western disjointed population of Sicily has been classified as an endemic sub-species, F. nodosa subsp. geniculata (Guss.) Troia & Raimondo, it is not officially accepted. From the aerial parts of the Sicilian accession of this species four known metabolites (1-4), and a new ferulol derivative (5), were isolated and characterized. The structure of the new compounds was determined by mean of extensive NMR spectroscopic experiments.


Effect of antimicrobial de-escalation strategy on 14-day mortality among intensive care unit patients: a retrospective propensity score-matched cohort study with inverse probability-of-treatment weighting.
This study aimed to investigate the prevalence of antimicrobial de-escalation (ADE) strategy and assess its effect on 14-day mortality among intensive care unit patients. A single-center retrospective cohort study was conducted on patients admitted to the intensive care unit (ICU) with infectious diseases between January 2018 and December 2020. Patients were stratified into three groups based on the initial treatment regimen within 5 days of antimicrobial administration: ADE, No Change, and Other Change. Confounders between groups were screened using one-way ANOVA and Chi-square analysis. Univariate and multivariate analyses were performed to identify risk factors for 14-day mortality. Potential confounders were balanced using propensity score inverse probability of treatment weighting (IPTW), followed by multivariate logistic regression analysis to evaluate the effect of ADE strategy on 14-day mortality. A total of 473 patients met the inclusion criteria, with 53 (11.2%) in the ADE group, 173 (36.6%) in the No Change group, and 247 (52.2%) in the Other Change group. The 14-day mortality rates in the three groups were 9.4%, 11.6%, and 21.9%, respectively. After IPTW, the adjusted odds ratio for 14-day mortality comparing No Change with ADE was 1.557 (95% CI 1.078-2.247, P = 0.0181) while comparing Other Change with ADE was 1.282(95% CI 0.884-1.873, P = 0.1874). The prevalence of ADE strategy was low among intensive care unit patients. The ADE strategy demonstrated a protective effect or no adverse effect on 14-day mortality compared to the No Change or Other Change strategies, respectively. These findings provide evidence supporting the implementation of the ADE strategy in ICU patients.


Compartmented chambers for studying neurotrophic factor action.
Neurotrophic factors released by target tissues maintain the survival and differentiation of innervating neurons. The manner by which these target-derived neurotrophic proteins communicate with innervating neurons has been actively pursued for over three decades. The present chapter describes a technique for preparing and maintaining compartmented chambers for culturing neurons derived from either superior cervical ganglia (sympathetic neurons) or dorsal root ganglia (sensory neurons). This system recapitulates the selective stimulation of neuron terminals that occurs in vivo following release of target-derived neurotrophins.


A feedforward loop of NLRC5 (de)ubiquitination keeps IKK-NF-κB in check.
Many receptors signal via adaptors to the IKK-NF-κB axis, transducing extracellular cues to transcriptional regulation. In this issue, Meng et al. (2015. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201505091) reveal that the IKK regulator NLRC5 shapes NF-κB activity through a feedforward loop of NLRC5 ubiquitination and deubiquitination, highlighting a new pathway modulating IKK-NF-κB activity.


Hypovitaminosis D in dogs with spirocercosis.
Spirocercosis in dogs is characterized by esophageal nodules that can undergo neoplastic transformation. Hypovitaminosis D has been associated with neoplasia formation. We hypothesized hypovitaminosis D in neoplastic spirocercosis and that it could be a risk factor for neoplastic transformation. To measure and compare vitamin D status, assessed by serum 25-hydroxyvitamin D [25(OH)D] concentrations in non-neoplastic (n = 25) and neoplastic (n = 26) spirocercosis client-owned dogs and healthy dogs (n = 24). Twenty-five non-neoplastic dogs, 26 neoplastic dogs, and 24 healthy dogs. Fifty-one dogs were randomly selected from 119 dogs diagnosed with spirocercosis presenting to our hospital, and further divided into non-neoplastic or neoplastic groups. Exclusion criteria included dogs less than 1 year old, with concurrent diseases, received corticosteroids, or treated prophylactically for spirocercosis. Serum 25(OH)D concentration was measured by high-performance liquid chromatography. Spirocercosis dogs' appetites were graded and compared. Serum 25(OH)D concentrations were significantly different among all groups (P < .001). 25-Hydroxyvitamin D concentrations were significantly lower in neoplastic group (median 30.7 nmol/L [range 14.7-62.2]) compared to non-neoplastic (median 52.7 nmol/L [range 19.1-129.7, P < .05]) and healthy groups (median 74.6 nmol/L [range 37.4-130.5, P < .005]). 25-hydroxyvitamin D concentrations were significantly lower in non-neoplastic spirocercosis dogs compared to healthy ones (P < .05). Neoplastic and non-neoplastic spirocercosis dogs had similar appetite scores (P = 1.0). 25-Hydroxyvitamin D concentrations were not significantly different between dogs with normal (P = .087) and abnormal (P = .125) appetites within neoplastic and non-neoplastic spirocercosis groups. Further studies are warranted to determine potential use of vitamin D treatment in spirocercosis and explore role of hypovitaminosis D in pathogenesis of malignant transformation.


Premedication before day surgery. A double-blind comparison of diazepam and placebo.
Premedication with diazepam 0.25 mg kg-1 by mouth was compared with placebo in a double-blind trial in patients undergoing day-case surgery under general anaesthesia. Diazepam decreased significantly preoperative discomfort and apprehension. The patients were discharged on time regardless of the type of premedication, and complaints at the time of discharge and on the following day could be related only to the length of anaesthesia and not to the type of premedication. Premedication given early in the morning remained effective for up to 6 h.


Neurological soft-signs and minor physical anomalies in schizophrenia: differential transmission within families.
Markers of vulnerability have been identified in schizophrenia, and among them, neurological soft-signs (NSS) and minor physical anomalies (MPAs) also seem to occur in biological relatives. The similarities of these developmental markers within families may depend on either genetic or non-genetic factors. The aim of the study was to investigate the intra-familial similarities of NSS and MPAs within 18 nuclear families (18 probands with schizophrenia and 36 of their non-psychotic parents). A general linear model showed similarities within families for NSS (intra-class coefficient [ICC] = 0.64; F = 2.6; df = 17.17; p = 0.02) but not for MPAs (ICC = -0.10; F = 0.7; df = 17.17; ns). We thus found a direct evidence for the intra-familial transmission of NSS but not of MPAs, suggesting that this morphological phenotypic trait could be more dependent on epigenetic influences.


Seed migration in prostate brachytherapy depends on experience and technique.
To determine seed loss and pulmonary migration rate over time in permanent seed prostate brachytherapy. We analyzed the first 495 patients treated in our department. All patients were treated with loose (125)I seeds with automated seed delivery system and real-time intraoperative planning. Pelvic fluoroscopic imaging was done 30 days after the implant. Patients were divided into five groups of 100 patients according to the order they were treated, and groups were compared using χ(2) test and one-way analysis of variance. A total of 22.8% of patients lost at least one seed. The highest percentage of patients losing any number of seeds was in the first 100. Thirty-eight percent lost at least one seed. This number decreased gradually and was only 9% in Patients 400-499. The mean total seed loss rate (number of seeds lost/number seeds implanted) changed significantly over time (p<0.001). There was a continuous significant (p<0.001) decline after the first 100 patients (1.25% for the first 100 patients) followed by a rise in Patients 300-399, followed by another decline (0.21% for the last 100 patients). The seed loss rate to the thorax changed significantly over time (p=0.009). It rose after an initial rate of 0.25-0.42% in Patients 200-299 and 300-399 and declined later to a rate of 0.21% in the last 100 patients. We found a learning curve for seed migration. Avoiding implanting seeds outside of the capsule and modern transrectal ultrasound imaging can help decrease migration.


Fluorescent imaging for cancer therapy and cancer gene therapy.
The translation of laboratory science into effective clinical cancer therapy is gaining momentum more rapidly than any other time in history. Understanding cancer cell-surface receptors, cancer cell growth, and cancer metabolic pathways has led to many promising molecular-targeted therapies and cancer gene therapies. These same targets may also be exploited for optical imaging of cancer. Theoretically, any antibody or small molecule targeting cancer can be labeled with bioluminescent or fluorescent agents. In the laboratory setting, fluorescence imaging (FI) and bioluminescence imaging (BLI) have long been used in preclinical research for quantification of tumor bulk, assessment of targeting of tumors by experimental agents, and discrimination between primary and secondary effects of cancer treatments. Many of these laboratory techniques are now moving to clinical trials. Imageable engineered fluorescent probes that are highly specific for cancer are being advanced. This will allow for the identification of tumors for staging, tracking novel therapeutic agents, assisting in adequate surgical resection, and allowing image-guided biopsies. The critical components of FI include (1) a fluorescent protein that is biologically safe, stable, and distinctly visible with a high target to background ratio and (2) highly sensitive optical detectors. This review will summarize the most promising optical imaging agents and detection devices for cancer clinical research and clinical care.


Retinal neural progenitors express topographic map markers.
Transplantation of neural stem cells for replacing neurons after neurodegeneration requires that the transplanted stem cells accurately reestablish the lost neural circuits in order to restore function. Retinal ganglion cell axons project to visual centers of the brain forming circuits in precise topographic order. In chick, dorsal retinal neurons project to ventral optic tectum, ventral neurons to dorsal tectum, anterior neurons to posterior tectum and posterior neurons to anterior tectum; forming a continuous point-to-point map of retinal cell position in the tectal projection. We found that when stem cells derived from ventral retina were implanted in dorsal host retina, the stem cells that became ganglion cells projected to dorsal tectum, appropriate for their site of origin in retina but not appropriate for their site of implant in retina. This led us to ask if retinal progenitors exhibit topographic markers of cell position in retina. Indeed, retinal neural progenitors express topographic markers: dorsal stem cells expressed more Ephrin B2 than ventral stem cells and, conversely, ventral stem cells expressed more Pax-2 and Ventroptin than dorsal stem cells. The fact that neural progenitors express topographic markers has pertinent implications in using neural stem cells in cell replacement therapy for replacing projecting neurons that express topographic order, e.g., analogous neurons of the visual, auditory, somatosensory and motor systems.


Evaluation of position dependency in non-apneic snorers.
The aims of this study are to determine the prevalence of position dependency in non-apneic snorers, as defined by the American Academy of Sleep Medicine (AASM) guidelines, and to investigate the influence of various factors such as BMI, neck circumference, age, gender, and sleep efficiency on sleeping position. A cohort of consecutive patients was screened for complaints of excessive snoring or symptoms suspicious for sleep disordered breathing. Overnight polysomnographic data were collected and non-apneic snorers who met all the inclusion criteria were selected for statistical analysis. To assess position-dependent snoring, the snore index (total snores/h) was used. Supine-dependent patients were defined as having a supine snore index higher than their total non-supine snore index. 76 patients were eligible for statistical analysis. Prevalence of position dependency in non-apneic snorers was 65.8% (p < 0.008). A stepwise regression showed that only BMI had a significant effect (p < 0.003) on the supine snore index. This is the first study that uses the AASM guidelines to accurately define non-apneic snorers (AHI < 5) and provides scientific evidence that the majority of non-apneic snorers are supine dependent. Furthermore, these results show that non-apneic snorers with a higher BMI snore more frequently in supine position. The use of sleep position therapy therefore, has the potential to play a significant role in improving snoring and its associated physical and psychosocial health outcomes in this population.


Parental and community risk factors for childhood self-harm thoughts and behaviours.
Childhood self-harm is rare but increasing in frequency. Little is known about risk factors specifically for self-harm in preteen children. We examined self-harm thoughts and behaviours in children aged 3-14 years in association with parental and community-level risk factors, using a large general population-based record linkage sample (n = 74,479). Parental factors were strongly associated with childhood self-harm, with over three-quarters of children with self-harm having a parent with a history of mental disorder and/or criminal offending. Community-level factors (socioeconomic deprivation, remote or regional location, and neighbourhood crime rate) were not associated with childhood self-harm after adjustment for confounding factors. Measures of self-harm thoughts and behaviours derived from administrative data likely underestimate the prevalence of self-harm in the population. Intergenerational transmission of risk factors is likely an important contributor to childhood self-harm.


Overexpression of cyclin A overrides the effect of p53 alterations in breast cancer patients with long follow-up time.
The tumour suppressor gene p53 and its protein controls critical cellular functions in cell cycle regulation as well as in apoptosis. Recently, in an in vitro study on breast cancer cell line MCF-7, the apoptotic function of p53 has been shown to be altered by overexpression of cyclin A. In this study we have demonstrated a similar association in a consecutive series of 166 breast cancer patients operated for invasive breast carcinomas. We detected mutations (exon 5-8) in the tumour tissue from 28 (16.0%) of the patients, and positive immunoreactivity of p53 protein was detected in tumour tissue samples from 32 (18.8%) patients. A statistically significant correlation between TP53 gene mutations and positive immunohistochemistry of p53 protein was observed (p = 0.0038). Mutations of the TP53 gene, as well as positive immunoreactivity to p53, were associated with poor prognosis (mutations p = 0.053, HR = 1.8, 95% CI 0.99-3.4; positive immunoreactivity p = 0.029, HR 1.33, 95% CI 1.0-1.7; mutation and/or positive immunoreactivity p = 0.015, HR 2.1, 95% CI 1.2-3.7) when cyclin A was not included in the survival analysis. However, when cyclin A overexpression was included, alteration of the p53 protein (mutations and/or positive immunoreactivity) lost its statistical power (p = 0.088). In a stratified survival analysis the OR fell from 3.0 (95% CI 1.2-8.3, p = 0.03) in the low-expression cyclin A stratum to 1.3 (95% CI 0.42-4.1, p = 0.77) in the overexpression cyclin A stratum.


Rational polytherapy in the treatment of acute seizures and status epilepticus.
We used a model of severe cholinergic status epilepticus (SE) to study polytherapy aimed at reversing the effects of seizure-induced loss of synaptic GABA(A) receptors and seizure-induced gain of synaptic NMDA receptors. Combinations of a benzodiazepine with ketamine and valproate, or with ketamine and brivaracetam, were more effective and less toxic than benzodiazepine monotherapy in this model of SE.


The role of the absence of Hyrtl's anastomosis in monochorionic pregnancy: Friend or foe?: A case report.
Hyrtl's anastomosis, an intra-arterial shunt, plays a protective role when the placental territories supplied by the umbilical arteries are different in size. Its absence is associated with an increased risk of poor outcomes in singleton pregnancy. However, the literature and studies on the effect of absent Hyrtl's anastomosis in twin placentas are rare. We present a case of a monochorionic diamniotic twin pregnancy complicated with type I selective fetal growth restriction (SFGR). Despite discordance in placental territory and cord insertion sites, the patient had an overall good pregnancy process, suggesting that the absence of Hyrtl's anastomosis may have played a benign role. The absence of Hyrtl's anastomosis in our case seemed to show a favorable effect, representing a finding of opposite effects in monochorionic placentas compared with singleton placentas.


Relation between adiponectin and bone mineral density in elderly post-menopausal women: role of body composition, leptin, insulin resistance, and dehydroepiandrosterone sulfate.
Adipocytokines have been proposed as new mediators of the protective effects of fat mass on the skeleton. The aim of this study was to test the relationship between adiponectin, leptin, and bone mineral density (BMD), independently of body composition, insulin resistance, and other factors known to affect bone metabolism. Thirty-six post-menopausal non-diabetic elderly women, with ages ranging from 66 to 77 yr took part in the study. In all subjects we evaluated body weight, height, body mass index (BMI), waist circumference, adiponectin, leptin, insulin, DHEAS, and homeostasis model assessment of insulin resistance (HOMA), as well as yr since menopause. Total body fat mass (FM) and BMD at whole body and femoral level were measured with Dual energy X-ray Absorptiometry (DXA). Volumetric BMD was defined as the ratio between total body BMD and height. Leptin was positively and adiponectin negatively related with whole body and femoral BMD. Positive associations between insulin, HOMA, DHEAS, and BMD measures were also found. After adjusting for FM, only adiponectin maintained a significant relation with whole body and femoral BMD; the strength of this association was reduced after adjustment for insulin resistance, estimated by HOMA. In stepwise multiple linear regression analyses adiponectin explained 11.7% of total BMD variance, 17.4% of femoral neck BMD variance, and 30.7% of volumetric BMD variance, independently of BMI, FM, leptin, HOMA, and DHEAS. The present study may suggest possible involvement of adiponectin in bone metabolism, independently of FM and insulin resistance even in elderly post-menopausal women.


Effect of decentralization or contralateral ganglionectomy on obstruction-induced hypertrophy of rat urinary bladder muscle and pelvic ganglion.
After urethral obstruction the musculature of the rat urinary bladder undergoes extensive hypertrophy, irrespective of whether its innervation is intact or whether one of the two pelvic ganglia has been decentralized or excised. Even the excision of both ganglia does not inhibit muscle hypertrophy. The presence of nerves is not a prerequisite for the muscle growth to occur. The stimulus for growth resides in the bladder itself, and the present and previous observations are in agreement with the notion that the distension of the muscle is a primary stimulus for muscle growth. With bladder hypertrophy, the pelvic ganglion neurons undergo hypertrophy, even when they are devoid of their preganglionic input. Synaptic connection with the preganglionic fibres and stimuli from the spinal cord are not prerequisites for neuronal hypertrophy. However, the hypertrophy is less marked in the decentralized ganglion neurons than in the neurons of the contralateral intact ganglion. With bladder hypertrophy and contralateral ganglionectomy, the neuronal hypertrophy is greater than with either procedure alone, suggesting that the two forms of neuronal growth stimulation can be added to each other.


Environmental impact of desalination processes: Mitigation and control strategies.
Freshwater supplies are in shortage relative to the high demand for different human activities, making desalination of saline water a must. Desalination to extract water from saline water has been well established as a reliable non-conventional water supply. However, desalination as any human-based process has resulted in many impacts on the environment. Brine loaded with chemicals being discharged back to the environment, along with greenhouse gases (GHGs) emissions being released to the atmosphere, are the most significant impacts, which has been extensively studied, with some efforts given to its mitigation and control. The current work discusses the mitigation and control strategies (M&CS) to the different environmental impacts (EIs) of desalination processes. The article compiles the M&CS in one work, instead of the distributed and separate treatment of the EIs of each desalination step and its respective M&CS as currently present in literature. The article tracks the water flow in an intake-to-outfall approach exploring how to minimize the impacts at each step and as a whole process. This starts from intake, pretreatment processes, desalination technology, and finally, brine discharge. The EIs associated with each desalination process element is thoroughly discussed with proposed M&CS. The work shows clearly that many EIs can be eliminated or minimized by incorporating specific design criteria and process improvements. The feedwater source has shown to have a great effect on EIs. Similarly, desalination technology has shown a considerable effect on the EIs related to brine characteristics and energy consumption. Hybrid and emerging desalination systems have shown reduced EIs relative to conventional thermal and membrane desalination technologies, while the utilization of renewable and waste energy sources has shown a significant reduction in EIs related to energy consumption.


Comparison Between Thulium Laser VapoEnucleation and GreenLight Laser Photoselective Vaporization of the Prostate in Real-Life Setting: Propensity Score Analysis.
To compare in daily practice efficacy and safety of standard 180-Watt GreenLight laser photoselective vaporization (PVP) and Thulium laser Vaporesection of the prostate (ThuVEP). All men were evaluated with prostate volume, prostate-specific antigen, International Prostate Symptom Score, and maximum urinary flow. Patient global impression of improvement was evaluated with patient global impression of improvement scale for 6 months. Antiplatelet/anticoagulant therapy, operation time, 24-hour hemoglobin drop , length of catheterization, discharge day, early complications, and reoperation after 30 days were gathered. Differences between interventions were estimated using propensity scores to adjust for different patients characteristics. The propensity scores were estimated by fitting a stepwise logistic regression model with intervention type as the dependent variable and all the covariates. Five hundred five men underwent the surgical procedures (291 PVP and 214 ThuVEP). Mean age was 69.6 years. Mean prostate volume was 54 mL. Median operation time was 55 minutes. Median catheterization time was 2 days in both series. After matching, the postoperative stay was similar in both groups (2 days). Hemoglobin drop for 24 hours was statistically significantly lower in PVP (-0.5 vs -0.8 g/dL, P .002). Most of the complications were mild-to-moderate and comparable among groups. Δ Maximum urinary flow was similar 6-month after surgery before and after matching, whereas PVP group had a better improvement 12-month after surgery. 96.4% of all patients had an improvement of their symptoms, with no difference between groups, before and after matching. Our study demonstrated that PVP and ThuVEP are similar in term of complications and outcomes, with high patients' satisfaction.


Methylation and gene expression of histone deacetylases 6 in systemic lupus erythematosus.
The purpose of this study is to investigate the role of methylation in the histone deacetylases 6 (HDAC6) promoter and HDAC6 messenger RNA (mRNA) expression in the pathogenesis of systemic lupus erythematosus (SLE). Direct bisulfite-polymerase chain reaction (PCR) sequencing was performed to detect the HDAC6 promoter methylation in 33 patients with SLE and 35 healthy controls. The HDAC6 mRNA expression was measured in 93 SLE patients and 84 healthy controls by using the method of quantitative real-time PCR. This study demonstrated that the methylation rates at HDAC6-680, -660 and -658 were significantly increased in the SLE patients compared with healthy controls (P = 0.041, 0.034 and 0.029, respectively). The SLE patients also had lower HDAC6 mRNA expression than the controls (P = 0.031). However, there was no significant difference in HDAC6 mRNA expression between patients with active and inactive SLE. The SLE patients had higher methylation in the HDAC6 promoter and lower HDAC6 mRNA expression than the controls. These changes may be related to the susceptibility of SLE. However, they are not associated with the disease activity of SLE.


The role of condensed tannins in the nutritional value of Lotus pedunculatus for sheep. 5. Effects on the endocrine system and on adipose tissue metabolism.
1. Three experiments were conducted using Lotus pedunculatus containing high concentrations of condensed tannins (CT), and utilizing the principle that polyethylene glycol (PEG) application (molecular weight 3350) will irreversibly bind a portion of the CT and thus reduce the dietary reactive (i.e. non-PEG bound) CT concentration. Lotus diets containing 95, 45 and 14 g total reactive CT/kg dry matter (DM), induced by spraying with three PEG rates, were given to sheep at hourly intervals (600 g DM/d) for 21 d (Expt 1). In Expts 2 and 3, lambs grazed areas oversown with either lotus (89 g CT/kg DM) or clovers (Trifolium repens and Trifolium pratense; less than 1 g CT/kg DM) for 42 and 92 d respectively. In Expt 2 half the animals grazing each forage received oral PEG (75 g/d), whilst in Expt 3 half the lambs were sired by rams selected respectively for low or high levels of subcutaneous fat deposition. 2. Hormone concentrations in plasma (Expt 1 only) were determined by radioimmunoassay. Rates of [U-14C]-acetate and D-[U-14C]glucose incorporation and oxidation by subcutaneous and abdominal adipose tissue removed at slaughter, together with rate of glycerol release, were determined during in vitro incubation in all three experiments. 3. Plasma concentration of growth hormone was positively and linearly related to dietary reactive CT concentration, whilst 3,5,3'-triiodothyronine (T3) concentration tended to be negatively and linearly related to dietary reactive CT concentration. Diet CT concentration had no effect on plasma concentrations of the other hormones measured.(ABSTRACT TRUNCATED AT 250 WORDS)


How did bacteria come to be?
Bacteria in the modern taxonomic sense are one of the three Domains. They must have split from the other two after the bulk of the development of biochemistry and cell biology had taken place. Up to the time of the Last Universal Ancestor (LUA) the world had been monophyletic with little stable diversity. This is to say that as advances took place the older forms were eliminated and diversity was only temporary. Two kinds of events could, in principle, permit stable diversity to arise. One kind occurs when two nearly simultaneous, different advances occur, both of which overcome the same problem. While the previous type would be supplanted, if the new types did not compete with each other, new niches and habitats could lead to stable diversity. The second kind is a saltation or macroevolutionary event that greatly expands the biota and reduces previous constraints and thereby drastically reduces competition; this generally leads to a 'species radiation' and results in the development of a spectrum of biological types some of which persist and do not compete with each other. It is proposed that the two splits to yield the three Domains of Bacteria, Archaea, and Eukarya, resulted from one of each of these two processes leading to diversity. One arose from the consequences of cells accumulating substances from the environment, thus increasing their internal osmotic pressure. This resulted in two nearly simultaneous biological solutions: one (Bacteria) was the development of the external sacculus, i.e. the formation of a stress-bearing exoskeleton. The other (Eukarya) was the development of cytoskeletons and mechanoenzymes, i.e. formation of an endoskeleton. The other event causing diversity was the invention of an effective way to tap a new energy source and allow the biomass to increase extensively permitting a radiation of many different types of organisms. I suggest that this seminal advance was the development of methanogenesis. This caused a short-lived expansion and radiation before oxygen-producing photosynthesis allowed a still more major expansion and decreased the number of methanogens. Some details of these processes are elaborated. In particular, the evolutionary process that permitted the development of a sacculus, interpreted in light of the bacterial physiology of today's organisms is presented. It is argued that many great advances arise by developing a number of totally different processes for other purposes that can then each be modified to combine for yet another purpose.


The structural basis for the interaction between nonsense-mediated mRNA decay factors UPF2 and UPF3.
Nonsense-mediated mRNA decay (NMD) is a surveillance mechanism by which eukaryotic cells detect and degrade transcripts containing premature termination codons. Three 'up-frameshift' proteins, UPF1, UPF2 and UPF3, are essential for this process in organisms ranging from yeast to human. We present a crystal structure at a resolution of 1.95 A of the complex between the interacting domains of human UPF2 and UPF3b, which are, respectively, a MIF4G (middle portion of eIF4G) domain and an RNP domain (ribonucleoprotein-type RNA-binding domain). The protein-protein interface is mediated by highly conserved charged residues in UPF2 and UPF3b and involves the beta-sheet surface of the UPF3b RNP domain, which is generally used by these domains to bind nucleic acids. We show that the UPF3b RNP does not bind RNA, whereas the UPF2 construct and the complex do. Our results advance understanding of the molecular mechanisms underlying the NMD quality control process.


Classification of Adolescent Psychiatric Patients at High Risk of Suicide Using the Personality Assessment Inventory by Machine Learning.
There are growing interests on suicide risk screening in clinical settings and classifying high-risk groups of suicide with suicidal ideation is crucial for a more effective suicide preventive intervention. Previous statistical techniques were limited because they tried to predict suicide risk using a simple algorithm. Machine learning differs from the traditional statistical techniques in that it generates the most optimal algorithm from various predictors. We aim to analyze the Personality Assessment Inventory (PAI) profiles of child and adolescent patients who received outpatient psychiatric care using machine learning techniques, such as logistic regression (LR), random forest (RF), artificial neural network (ANN), support vector machine (SVM), and extreme gradient boosting (XGB), to develop and validate a classification model for individuals with high suicide risk. We developed prediction models using seven relevant features calculated by Boruta algorithm and subsequently tested all models using the testing dataset. The area under the ROC curve of these models were above 0.9 and the RF model exhibited the best performance. Suicide must be assessed based on multiple aspects, and although Personality Assessment Inventory for Adolescent assess an array of domains, further research is needed for predicting high suicide risk groups.


Who uses a mobile phone while driving for food delivery? The role of personality, risk perception, and driving self-efficacy.
The existing literature on mobile phone use while driving (MPUWD) mainly targets the participants from general population and the young adults, however, few studies pay attention to this form of distracted driving with samples in professional contexts. The present study aims to bridge the gap by identifying the extent of and the motives behind making use of mobile phones while driving for food dispatch among deliveryman. The snowball sampling was used to collect the data (N = 317) through a self-reported questionnaire, including demographics, personality traits, risk perception, driving self-efficacy, and mobile phone use while driving. Descriptive analysis for the assessed MPUWD behaviors showed that 96.3% (N = 315) of food deliveryman undertook the MPUWD behaviors, though disproportionate distribution among these behaviors existed. Structural equation modeling analysis displayed that psychoticism and driving self-efficacy directly predicted the MPUWD behaviors. The mediating role of driving self-efficacy was verified with the findings that driving self-efficacy completely mediated the relationships that between risk perception and MPUWD behaviors and that between extraversion and MPUWD behaviors, as well as partially mediated the correlation between psychoticism and MPUWD behaviors. The present study confirms the prevalence of MPUWD behaviors among food deliveryman. The SEM estimates and bootstrap estimates suggest that personality traits and perceived risk perception per se display limited predicting utility to MPUWD behaviors among food deliveryman, whereas driving self-efficacy and the proposed predictors together well illustrate the assessed MPUWD behaviors among food deliveryman. Practical Applications: These findings imply that developing and implementing intervention efforts in a concerted way would curb these behaviors effectively.


A Prospective Comparison of the 21-Gene Recurrence Score and the PAM50-Based Prosigna in Estrogen Receptor-Positive Early-Stage Breast Cancer.
The 21-gene Recurrence Score(®) assay (Oncotype DX(®), Genomic Health, Inc.) is a validated predictor of recurrence risk/chemotherapy benefit in patients with estrogen receptor-positive (ER+) early-stage breast cancer treated with endocrine therapy. The Prosigna(®) assay (NanoString Technologies Inc.) is a validated prognosticator in postmenopausal patients with low-risk ER+ early-stage breast cancer treated with endocrine therapy. The assays were analytically/clinically developed and validated differently. This study focused on comparing recurrence risk estimates as determined by these assays and is the first blinded comparison of these assays on matched patient samples. Sequential breast cancer specimens from postmenopausal, node-negative, ER+ patients treated at the Marin General Hospital were analyzed: first by the 21-gene assay then by the Prosigna assay in an independent lab blinded to the Recurrence Score results. The final analysis included 52 patients. Correlation between the Recurrence Score and the Prosigna assay results was poor (r = 0.08). Agreement between risk classifications based on these assays was 54%; 4/7 of patients classified as high risk by the Prosigna assay had low Recurrence Score results. Two tumors with high Recurrence Score results had low ER expression (close to positivity threshold); both of which had a low/intermediate Prosigna assay result. The Prosigna assay classified 73.1% and 23.1% of samples as luminal A and luminal B, respectively. A range of Recurrence Score results was observed within the subtypes; 83% of luminal B samples had a low Recurrence Score result. Consistent with prior comparisons between the 21-gene and other genomic assays, our study demonstrated substantial differences in the way patients are risk stratified, suggesting that the different assays are not interchangeable. Genomic Health, Inc.


[Esophageal carcinoma: novelties and challenges in surgery].
Surgical resection of esophageal carcinoma is one of the mainstays of curative treatment for these cancers. During the last decade, numerous improvements in surgical approaches and perioperative management of these patients have resulted in a decrease in postoperative morbidity and mortality. Thus, centralization of patients with esophagogastric adenocarcinoma in high volume center, development of minimally invasive surgery and improvements in surgical imaging have led to reduce mortality rate, major pulmonary complication rate and postoperative chylothorax rate. Optimization of postoperative management with enhanced recovery programs has meanwhile reduced the rate of major postoperative complication and the hospital length of stay. The objective of this review is to give an overview of novelties and challenges regarding surgical management of patients with esophageal carcinoma.


The activation of M3 mAChR in airway epithelial cells promotes IL-8 and TGF-β1 secretion and airway smooth muscle cell migration.
Muscarinic acetylcholine receptors (mAChRs) have been identified in airway epithelium, and epithelium-derived chemokines can initiate the migration of airway smooth muscle (ASM) cells. However, the mAChRs that are expressed in airway epithelium and the mechanism underlying the regulation of ASM cell migration are not clear. The aim of this study was to test whether the effects of the epithelium-derived chemokines on ASM cell migration could be modulated by mAChRs. Human epithelial cells (A549 cells) were stimulated with cigarette smoke extract (CSE) or the mAChRs agonist carbachol. IL-8 and TGF-β1 production were measured by ELISA, and human ASM cell migration was measured using the transwell migration assay and scratch assay. The mRNA levels of the mAChRs subtypes and the acetylcholine concentrations were measured using RT-PCR and LC-MS/MS, respectively. ASM cell migration toward CSE-stimulated A549 cells was markedly reduced by Ac-RRWWCR-NH2 (IL-8 inhibitor) and SB431542 (TGF-β1 inhibitor). CSE-induced ASM cell migration was also suppressed by the mAChRs antagonist tiotropium. Interestingly, carbachol-stimulated A549 cells also induced ASM cell migration; this migration event was suppressed by tiotropium, Ac-RRWWCR-NH2 and SB431542. In addition, the effects of CSE on ASM cell migration were significantly and cooperatively enhanced by carbachol compared to CSE alone. Carbachol-induced ASM cell migration was reduced by selective inhibitors of PI3K/Akt (LY294002) and p38 (SB203580), suggesting that it occurred through p38 and Akt phosphorylation, which was inhibited by the M3 mAChR antagonist 4-DAMP. These findings indicate that M3 mAChR may be important therapeutic target for obstructive airway diseases, as it regulates the effects of the epithelial-derived chemokines on ASM cell migration, which results in lung remodeling.


Plasma Trimethylamine N-Oxide, a Gut Microbe-Generated Phosphatidylcholine Metabolite, Is Associated With Atherosclerotic Burden.
Trimethylamine N-oxide (TMAO), a gut microbiota metabolite from dietary phosphatidylcholine, has mechanistic links to atherosclerotic coronary artery disease (CAD) pathogenesis and is associated with adverse outcomes. This study sought to examine the relationship between plasma TMAO levels and the complexity and burden of CAD and degree of subclinical myonecrosis. We studied 353 consecutive stable patients with evidence of atherosclerotic CAD detected by elective coronary angiography between 2012 and 2014. Their high-sensitivity cardiac troponin T (hs-cTnT) levels were measured. SYNTAX (Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery) scores and lesion characteristics were used to quantify atherosclerotic burden. Fasting plasma TMAO was measured by mass spectrometry. In this prospective cohort study, the median TMAO level was 5.5 μM (interquartile range [IQR]: 3.4 to 9.8 μM), the median SYNTAX score was 11.0 (IQR: 4.0 to 18.5), and 289 (81.9%), 40 (11.3%), and 24 (6.8%) patients had low (0 to 22), intermediate (23 to 32), and high (≥33) SYNTAX scores, respectively. Plasma TMAO levels correlated (all p < 0.0001) with the SYNTAX score (r = 0.61), SYNTAX score II (r = 0.62), and hs-cTnT (r = 0.29). Adjusting for traditional risk factors, body mass index, medications, lesion characteristic, renal function, and high-sensitivity C-reactive protein, elevated TMAO levels remained independently associated with a higher SYNTAX score (odds ratio [OR]: 4.82; p < 0.0001), SYNTAX score II (OR: 1.88; p = 0.0001), but were not associated with subclinical myonecrosis (OR: 1.14; p = 0.3147). Elevated TMAO level was an independent predictor of the presence of diffuse lesions, even after adjustments for traditional risk factors and for hs-cTnT (OR: 2.05; 95% confidence interval: 1.45 to 2.90; p = 0.0001). Fasting plasma TMAO levels are an independent predictor of a high atherosclerotic burden in patients with CAD.


Selective functionalization of benzylic C-H bonds of two different benzylic ethers by bowl-shaped N-hydroxyimide derivatives as efficient organoradical catalysts.
A highly efficient, site-selective benzylic C-H bond amination of two different benzylic ether substrates was described by using bowl-shaped N-hydroxyimide organoradical catalysts with diethyl azodicarboxylate. The synthetic utility of this approach is demonstrated by the subsequent transformation of the amination products into the corresponding aldehydes and alkylhydrazines.


Baclofen toxicity in an 8-year-old with an intrathecal baclofen pump.
Baclofen delivered by intrathecal pumps (ITB) is increasingly being utilized in the pediatric population, however, resources and education to support problems with these devices are limited. Typical management strategies for systemic baclofen overdose include removal of baclofen from the device reservoir or removal of cerebrospinal fluid from the adjacent device catheter. Appropriate care of these patients requires awareness of the clinical patterns of toxicity and mechanics of the ITB pump delivery system. This report describes the clinical presentation, unfamiliar dilemmas, and the management of a pediatric patient with intrathecal baclofen toxicity, noting problems that may arise in the care of these patients.


The MIG1 repressor from Kluyveromyces lactis: cloning, sequencing and functional analysis in Saccharomyces cerevisiae.
Sequence comparisons between Saccharomyces cerevisiae ScMig1 and Aspergillus nidulans CREA proteins allowed us to design two sets of degenerate primers from the conserved zinc finger loops. PCR amplification on Kluyveromyces marxianus and K. lactis genomic DNA yielded single products with sequences closely related to each other and to the corresponding regions of ScMig1 and CREA. The KIMIG1 gene of K. lactis was cloned from a genomic library using the K. marxianus PCR fragment as probe. KIMIG1 encodes a 474-amino acid protein 55% similar to ScMig1. Besides their highly conserved zinc fingers, the two proteins display short conserved motifs of possible significance in glucose repression. Heterologous complementation of a mig1 mutant of S. cerevisiae by the K. lactis gene demonstrates that the function of the Mig1 protein is conserved in these two distantly related yeasts.


Early alcohol experiences and adolescent mental health: a population-based study in Taiwan.
In this study, we examine whether adolescent emotional and behavior problems vary by history of early alcohol experiences. A national sample of 6974 alcohol-naïve and 4337 alcohol-experienced youths aged 15-18 years were identified within the 2004 National Survey of Illegal Drug Use among Adolescents in Taiwan. Four alcohol experience groups were created based on recency and frequency of alcohol use: (1) naïve; never drank alcohol, (2) trial use; first and only consumption of alcohol occurred more than 6 months preceding the assessment, (3) past use; alcohol used on more than one occasion but had not had a drink in the 6 months prior to the assessment, and (4) current use; consumed alcohol more than once and drank within the 6 months preceding the interview. A Chinese adaptation of the Youth Self-Report (YSR) assessed eight behavior syndromes: withdrawn, anxious/depressed, somatic complaints, social problems, thought problems, attention problems, rule-breaking behavior, and aggressive behavior. Multivariate response models (GLM/GEE) were used to examine the relationship of alcohol experiences with emotional and behavior problems. Alcohol-using youth were more likely to experience several specific emotional or behavioral syndromes than their alcohol-naïve counterparts. For example, youth with a history of alcohol use had an estimated 30-60% increase in the odds of experiencing items within the aggressive behavior syndrome as compared with alcohol-naïve youth. The type of early alcohol involvement in adolescence may exert differential effects on emotions and behaviors expressed across and within syndromes; these may warrant distinctions in informing etiological research and preventive efforts.


NSAIDs in the treatment and/or prevention of neurological disorders.
Non-steroidal anti-inflammatory drugs (NSAIDs) have been used extensively in the treatment of inflammatory disorders and pain. In recent years, emerging data suggest that some NSAIDs possess pharmacological properties, in addition to cyclooxygenase inhibition, which may be beneficial in the treatment of several neurological conditions. For example, fenamate NSAIDs potentiate GABA-A receptor function, indomethacin scavenges nitric oxide free radicals, and acetylsalicylic acid inhibits the translocation of NF-κB, all of which may contribute to their neuroprotective actions in selected experimental models of stroke. The purpose of this review is to explore the diverse pharmacological properties of NSAIDs in relation to their potential value in the treatment of selected neurological diseases.


Flexible frequency selective metamaterials for microwave applications.
Metamaterials have attracted more and more research attentions recently. Metamaterials for electromagnetic applications consist of sub-wavelength structures designed to exhibit particular responses to an incident EM (electromagnetic) wave. Traditional EM (electromagnetic) metamaterial is constructed from thick and rigid structures, with the form-factor suitable for applications only in higher frequencies (above GHz) in microwave band. In this paper, we developed a thin and flexible metamaterial structure with small-scale unit cell that gives EM metamaterials far greater flexibility in numerous applications. By incorporating ferrite materials, the thickness and size of the unit cell of metamaterials have been effectively scaled down. The design, mechanism and development of flexible ferrite loaded metamaterials for microwave applications is described, with simulation as well as measurements. Experiments show that the ferrite film with permeability of 10 could reduce the resonant frequency. The thickness of the final metamaterials is only 0.3mm. This type of ferrite loaded metamaterials offers opportunities for various sub-GHz microwave applications, such as cloaks, absorbers, and frequency selective surfaces.


Elevated red cell distribution width is associated with negative P wave amplitude in lead V1: national health and nutrition examination survey (NHANES III).
Red cell distribution (RDW) is associated with atrial fibrillation (AF) incidence. However, its relationship with precursors of AF has not been established. We aim to investigate if association exists between RDW and negative P wave amplitude in V1, a marker of left atrial abnormality. NHANES III is a complex, multistage, clustered design survey of noninstitutionalized United States population between 1988-94. A Sample of 6403 individuals was extracted after excluding missing demographic, laboratory, anthropometric and ECG data and major ECG abnormalities. Variables were selected and univariate analysis was done first with a level of significance at P<0.01 (99% confidence). All the significant variables were included in a multivariate linear regression model. 53.58% of subjects were female. Racial distribution was caucasian 50.2%, hispanic 23.9% and african american 21.7%. Age, PR interval, heart rate, systolic blood pressure, red cell distribution width, glycated hemoglobin, serum cholesterol, serum ferritin, and body mass index showed a significant correlation with negative P wave amplitude in V1 (P<0.001). After including all these variables in a multivariate regression model, only age, body mass index, systolic blood pressure, PR interval, heart rate and red cell distribution width had a P≤0.001. Increased RDW is independently associated with negative P wave amplitude in V1 after correcting for other cardiovascular risk factors. Further studies are required to analyze the reason for this correlation.


Jordanian National Study of Nurses' Barriers and Predictors for Research Utilization in Clinical Settings.
The nurses are the healthcare providers and researchers in the health institutions. Investment in the research potential of nurses will ultimately benefit society. The purpose of this study was to survey nurses regarding barriers to participating in research studies. This was a cross-sectional descriptive study using electronic surveys sent by email, and social media groups (WhatsApp). A total of 447 nurses agreed to participate in this study. Barriers were measured using the Barriers of Research Utilization (BRU) Scale. More than half (53.3%) of the participants perceived the barriers to be high, whereas a small fraction (8.9%) perceived them as low. Barriers related to the organization scored the highest (P<0.01) compared to the other domains (nurse, innovation, and communication). The regression analysis model showed that age, working experience, and nationality were associated with barriers to participate in research (P<0.05). More than half of the nurses in Jordan perceived barriers to participating in research studies to be high. The barriers associated with the organization had more influence. A comprehensive approach should be developed to boost research utilization among nurses by overcoming the barriers identified in the current study.


A gain-of-function mutation in PDR1 of Candida glabrata decreases EPA1 expression and attenuates adherence to epithelial cells through enhancing recruitment of the Mediator subunit Gal11A.
Genetic studies have revealed critical roles of transcription factor Pdr1 and the Mediator subunit Gal11A in regulating azole resistance in Candida glabrata. Recently, PDR1 gain-of-function (GOF) mutations have been shown to not only increase azole resistance but also enhance adherence during C. glabrata infection. However, mechanism of how Pdr1 regulates adherence, especially the implication of PDR1 GOF mutations in the regulation of the major adhesin gene EPA1, remains uncharacterized. Initially, we unexpectedly observed that expression of PDR1 harbouring GOF mutation G346D down-regulated EPA1 transcription and attenuated adherence to epithelial cells in different strain backgrounds. Given that PDR1 GOF mutations have been previously regarded as stimulators for adherence of this species, these findings prompted us to explore the regulation of EPA1 by wild-type Pdr1 and Pdr1 harbouring G346D mutation. Epitope tagged version of Pdr1 and Gal11A were utilized to determine the association of Pdr1 and Gal11A with EPA1 promoter. A combination of approaches including deletion, molecular, and biochemical assays showed that EPA1 is a direct target of Pdr1, and demonstrated for the first time that PDR1 G346D mutation decreases EPA1 expression and attenuates adherence to epithelial cells via enhancing recruitment of Gal11A. Taken together, our data propose a critical role of Gal11A in Pdr1-regulated EPA1 expression and adherence to epithelial cells, which could be utilized a novel therapeutic target for the treatment of hyper-adherent C. glabrata infection.


[Daptomycin in Gram-positive bacterial infections in oncohematological patients and transplant recipients].
Gram-positive infections are a major cause of morbidity and mortality in oncohematological patients and transplant recipients. The most frequently isolated Gram-positive organisms are the coagulase-negative staphylococci, Staphylococcus aureus and Enterococcus spp., and viridans group streptococci. Antibiotic resistance in these organisms is increasing and poses a challenge to clinicians. Daptomycin is rapidly bactericidal against a broad spectrum of gram-positive bacteria, including strains resistant to other drugs. The present article reviews some aspects of Gram-positive infections in these immunocompromised patients and provides a detailed analysis of experience with daptomycin in the treatment of these infections.


Kras-mutation influences outcomes for palliative primary tumor resection in advanced colorectal cancer-a Turkish Oncology Group study.
We aimed to investigate the prognostic effect of primary tumor resection (PTR) prior to bevacizumab-based treatments in unresectable metastatic colorectal cancer (mCRC). We retrospectively collected 341 mCRC cases with unresectable metastases at diagnosis. PTR was performed in 210 cases (the surgery group) and the other patients (n = 131) were followed without PTR (the no-surgery group). All the patients were treated with bevacizumab combined chemotherapy regimens. The median progression free survival (PFS) of the surgery group was 10.4 months (95% CI: 8.9-11.9), which was significantly better than that of the no-surgery group (7.6 months, 95% CI: 6.4-8.8, P=0.000). The median overall survival (OS) of the surgery group was longer than that of the no-surgery group (27.4 months vs. 18.3 months, respectively, P=0.000). The median PFS and OS of the surgery group were 10.4 months and 28.2 months, which were significantly longer than that of the no-surgery group in Kras-mutant patients (7.8 months and 18.3 months; P=0.004, P=0.028, respectively). There was no difference in terms of PFS and OS between the surgery and the no-surgery groups in Kras-wild type patients. Palliative PTR may improve the survival outcomes for unresectable mCRC patients. PTR may be preferred, particularly in Kras-mutant patients.


Distinguishing automatic and controlled components of attitudes from direct and indirect measurement methods.
Distinct automatic and controlled processes are presumed to influence social evaluation. Most empirical approaches examine automatic processes using indirect methods, and controlled processes using direct methods. We distinguished processes from measurement methods to test whether a process distinction is more useful than a measurement distinction for taxonomies of attitudes. Results from two studies suggest that automatic components of attitudes can be measured directly. Direct measures of automatic attitudes were reports of gut reactions (Study 1) and behavioral performance in a speeded self-report task (Study 2). Confirmatory factor analyses comparing two-factor models revealed better fits when self-reports of gut reactions and speeded self-reports shared a factor with automatic measures versus sharing a factor with controlled self-report measures. Thus, distinguishing attitudes by the processes they are presumed to measure (automatic vs. controlled) is more meaningful than distinguishing based on the directness of measurement.


Factors affecting achievement of glycemic targets among type 2 diabetes patients in South Asia: Analysis of the CARRS trial.
To assess the predictors of achieving and maintaining guideline-recommended glycemic control in people with poorly controlled type 2 diabetes. We analyzed data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) Trial (n = 1146), to identify groups that achieved guideline-recommended glycemic control (HbA1c < 7%) and those that remained persistently poorly controlled (HbA1c > 9%) over a median of 28 months of follow-up. We used generalized estimation equations (GEE) analysis for each outcome i.e. achieving guideline-recommended control and persistently poorly controlled and constructed four regression models (demographics, disease-related, self-care, and other risk factors) separately to identify predictors of HbA1c < 7% and HbA1c > 9% at the end of the trial, adjusting for trial group assignment and site. In the final multivariate model, adherence to prescribed medications (RR: 1.46, 95%CI: 1.09, 1.95), adherence to diet plans (RR: 1.79, 95% CI: 1.43, 2.23) and middle-aged: 50-64 years (RR: 1.32; 95% CI: 1.02-1.71) were associated with achieving guideline-recommended control (HbA1c < 7%). Presence of microvascular complications (RR: 0.70; 95%CI: 0.53-0.92) reduced the probability of achieving guideline-recommended glycemic control (HbA1c 7%). Further, longer duration of diabetes (>15 years), RR: 1.41; 95% CI: 1.15, 1.72, hyperlipidemia, RR: 1.19; 95% CI: 1.06, 1.34 and younger age group (35-49 years vs. >64 years: RR: 0.61; 95% CI: 0.47-0.79) were associated with persistently poor glycemic control (HbA1c > 9%). To achieve and maintain guideline-recommended glycemic control, care delivery models must put additional emphasis and effort on patients with longer disease duration, younger people and those having microvascular complications and hyperlipidemia.


Sulfate as a pivotal factor in regulation of Serratia sp. strain S2B pigment biosynthesis.
In the present work, we investigated the prodiginine family as secondary metabolite members. Bacterial strain S2B, with the ability to produce red pigment, was isolated from the Sarcheshmeh copper mine in Iran. 16S rDNA gene sequencing revealed that the strain was placed in the Serratia genus. Pigment production was optimized using low-cost culture medium and the effects of various physicochemical factors were studied via statistical approaches. Purification of the produced pigment by silica gel column chromatography showed a strong red pigment fraction and a weaker orange band. Mass spectrometry, FT-IR spectroscopy and (1)H NMR analysis revealed that the red pigment was prodigiosin and the orange band was a prodigiosin-like analog, with molecular weights of 323 and 317 Da, respectively. Genotoxicity and cytotoxicity studies confirmed their membership in the prodiginine family. Analysis of the production pattern of the pigments in the presence of different concentrations of ammonium salts revealed the role of sulfate as an important factor in regulation of the pigment biosynthesis pathway. Overall, the data showed that regulation of the pigment biosynthesis pathway in Serratia sp. strain S2B was affected by inorganic micronutrients, particularly the sulfate ions.


Effects of low-protein diet on the baroreflex and Bezold-Jarisch reflex in conscious rats.
The present study evaluated the effects of a low-protein diet (LP, 6% protein) on cardiovascular reflexes of Male Fisher rats. Three experimental groups, and their respective controls (15% protein), were used: (1) Baroreceptor reflex (BAR); (2) Bezold-Jarisch reflex (BJR); and (3) Prazosin treated. Dietary restriction began after weaning (three weeks) and lasted for a period of five weeks, after which animals were subjected to the experimental protocols. The BAR group was evaluated through injections of phenylephrine (0.5-5.0 microgram/Kg, i.v.) and sodium nitroprusside (0.7-7.0 microgram/Kg, i.v.) while the BJR was evaluated through injections of serotonin (2.5-10 microgram/Kg, i.v.). Our results showed an increased baroreflex gain bradycardia for the LP group (-0.96+/-0.34 vs. -2.12+/-1.06 bpm/mmHg) and a larger bradycardia for the BJR the LP group (160+/-18% greater than controls). Basal cardiovascular parameters were not different between LP and control rats, however LP animals treated with prazosin resulted in a larger fall of blood pressure (-19+/-3 vs. -28+/-5 mmHg). In conclusion, LP rats present an increased responsiveness of BAR and BJR, which could contribute to their normal levels of cardiovascular parameters, in spite of the possible increase in the sympathetic vasomotor tonus observed with the prazosin protocol.


gamma-Ray mutagenesis of cultured mammalian cells in vitro and in vivo.
The in vitro assay system used to study the reversion of L5178Y-Ala32 cells from an alanine requiring state to a non-requiring state has been modified in order to be of use in selected in vivo systems. Gamma-ray induced mutations were compared between cells cultured in vitro and those grown in vivo in the intraperitoneal cavity of mice. The expression time was chosen to be 2 days for cells grown in vitro and 5 days for those grown in vivo. The dose response curve can be described as cumulative for cells grown in vitro and linear for those grown in vivo. A dose-rate effect was observed in both systems. The cells grown in vivo were less sensitive to gamma-ray with respect to both mutation rate per rad and cell killing as compared to cells grown in vitro. The delayed expression and reduced sensitivity of cells in vivo with respect to induced mutation may be due to factors such as hypoxia and/or reduced availability of essential nutrients. Sensitization in vitro by BUdR was detectable at a concentration as low as 10(-6) M, using an exposure time of 15 h. Under these conditions, BUdR alone did not induce any observable mutations.


A comparison of the endoscopic and laparoscopic view of the gastroesophageal junction in the use of transoral fundoplication.
Endoscopic fundoplication requires accurate evaluation of the gastroesophageal junction (GJ) to determine if hiatal hernia repair is necessary before fundoplication. We compared the endoscopic and laparoscopic evaluations of the GJ. A total of 53 patients with gastroesophageal reflux disease underwent a laparoscopic repair of a hiatal defect before endoscopic fundoplication. The video of the preoperative endoscopic evaluation was compared with the laparoscopic video (n = 44). Nine patients were excluded because both endoscopic and laparoscopic videos were not available. A 2-tailed paired t test was used to assess the difference between the 2 study groups. The greatest transverse dimension of the hiatus assessed endoscopically was 3.30 cm ± 1.00 vs 3.88 cm ± 1.03 assessed laparoscopically, P < .001. In 22.8%, the average endoscopic Hill grade was lower than the estimated Hill grade when viewed laparoscopically. In 11.1% (range, 6% to 15%) of cases, the endoscopic view indicated a hiatal hernia repair was unnecessary when the matching laparoscopic view indicated hiatal repair would be needed. Endoscopic evaluation of the GJ may underestimate the radial size of the hiatal defect.


The complete sequence of Bacillus phage phi 29 gene 16: a protein required for the genome encapsidation reaction.
We have sequenced the region of the Bacillus phage phi 29 genome that encodes gene 16, the gene product of which catalyzes the in vivo and in vitro genome-encapsidation reaction. The identity of the coding frame was confirmed by sequencing a sus mutant, sus16(300). It is concluded that gene 16 encodes a 39-kDal protein and is comprised of 331 amino acids. Only 30 bp separates gene 16 from the last open reading frame of the right early region. Analysis of potential secondary structures in this region suggests that the same sequences may be involved in the termination of both the late and early transcripts.


Abnormality in cultured oligodendrocytes and Schwann cells isolated from the twitcher mouse.
Oligodendrocytes and Schwann cells were isolated from the brain and dorsal root ganglia of the twitcher mouse, a murine model of Krabbe's disease (globoid cell leukodystrophy), and grown in tissue culture. Oligodendrocytes were cultured for up to 22 d in vitro and were immunostained with a galactocerebroside antibody, a specific marker for oligodendrocytes. The control oligodendrocytes developed well-branched processes and membrane sheets, whereas the twitcher oligodendrocyte had wirelike processes with no membrane expansion and progressive degeneration. Schwann cells from the twitcher could not extend their processes as long as normal counterparts. The amounts of psychosine in the enriched population of oligodendrocytes and Schwann cells from the twitcher mouse are about 50-fold and 70-fold higher, respectively, than those in the control cells. These data suggest that psychosine may play an important role in the progression of abnormal features of oligodendroglial membrane formation and in the absence of process elongation in Schwann cells in the twitcher mutant.


Diospyros malabarica fruit preparation mediates immunotherapeutic modulation and epigenetic regulation to evoke protection against non-small cell lung cancer (NSCLC).
Diospyros malabarica is an ethnomedicinal plant with hypoglycaemic, anti-bacterial, and anti-cancer properties and it belongs to the Ebenaceae family which is well known for its medicinal uses since ancient times and application of its bark and unripened fruit has been significantly mentioned in Ayurvedic texts. The Diospyros malabarica species which is known as the Gaub in Hindi and Indian Persimmon in English is native to India, however, it is distributed throughout the tropics. As Diospyros malabarica fruit preparation (DFP) possesses medicinal values, the study aims to evaluate its role as natural, non-toxic, and cost-effective dendritic cells (DCs) maturing immunomodulatory agent and also as an epigenetic regulator to combat Non-small cell lung cancer (NSCLC) which is a type of lung cancer whose treatment options such as chemotherapy, radiation therapy, etc. are accompanied with some adverse side effects. Thus, immunotherapeutic strategies are in high demand to evoke tumor protective immunity against NSCLC without causing such side effects. Peripheral Mononuclear Cells (PBMCs) derived monocytes of normal subjects and NSCLC patients were utilized to generate DCs matured with either LPS (LPSDC) or DFP (DFPDC). Mixed Lymphocyte Reaction (MLR) was carried out with the differentially matured DCs co-culturing T cells and cytotoxicity of lung cancer cells (A549) was measured through LDH release assay and cytokine profiling was carried out via ELISA respectively. PBMCs of normal subjects and NSCLC patients have transfected separately in vitrowith CRISPR-activation plasmid of p53 and CRISPR-Cas9 knockout plasmid of c-Myc to analyze epigenetic mechanism(s) in the presence and absence of DFP. Diospyros malabarica fruit preparation (DFP) treated DC upregulates the secretion of T helper (TH)1 cell specific cytokines (IFN-γ and IL-12) and signal transducer and activator of transcription molecules (STAT1 and STAT4). Furthermore, it also downregulates the secretion of TH2-specific cytokines (IL-4 and IL-10). Diospyros malabarica fruit preparation (DFP) enhances p53 expression by reducing methylation levels at the CpG island of the promoter region. Upon c-Myc knockout, epigenetic markers such as H3K4Me3, p53, H3K14Ac, BRCA1, and WASp were enhanced whereas H3K27Me3, JMJD3, and NOTCH1 were downregulated. Diospyros malabarica fruit preparation (DFP) not only increases the expression of type 1 specific cytokines but also augments tumor suppression modulating various epigenetic markers to evoke tumor protective immunity without any toxic activities.


Peritoneal cytology of uncommon ovarian tumors.
Peritoneal cytology has been well established as a diagnostic and staging tool in the management of the common epithelial tumors of ovary. Germ cell, mesenchymal, and sex-cord stromal tumors are much less frequently encountered in peritoneal specimens, often with cytologic features that may pose problems in differential diagnosis. This report presents the cytomorphology of the ascitic fluid in cases of endodermal sinus tumor, dysgerminoma, and Sertoli-Leydig-cell tumor, and peritoneal washings in a case of ovarian malignant mixed mullerian tumor. The cytologic features of Sertoli-Leydig-cell tumors have not been well described. Careful correlation of peritoneal cytologic findings, cell-block preparations, and immunocytochemistry with the cytohistologic features of these tumors is crucial for correct tumor classification.


Safe intrahospital transport of critically ill ventilator-dependent patients.
To determine whether manual ventilation during intrahospital transport of mechanically ventilated critically ill patients results in blood gas and/or hemodynamic abnormalities. A single-blind prospective study evaluated arterial blood gas, blood pressure, heart rate, and arrhythmia changes during mechanical ventilation and manual transport ventilation. University hospital ICUs and various diagnostic or treatment areas. Twenty mechanically ventilated critically ill patients during intrahospital transport. Each patient received mechanical ventilation (MECH) with a volume ventilator while in the ICU and at the study/treatment area. They were manually ventilated (MAN) by a respiratory therapist during transport between areas. The MECH settings were: VT = 0.75 +/- 0.17 L; f = 16 +/- 4; VE = 12.6 +/- 4.3 L/min; FIO2 = 0.46 +/- 0.2. Mean peak Paw = 31 +/- 12 cm H2O and mean effective Cst = 44 +/- 15 ml/cm H2O. No hemodynamic abnormalities were observed. Arterial blood gas values did not vary to any clinically significant degree, except in two patients: one patient had a reduced PaO2 and increased PaCO2 associated with an accidental O2 disconnection and clamped chest tube; another patient had an increased pH by 0.13 units with only a 9 mm Hg fall in PaCO2. Manual ventilation during intrahospital transport of critically ill mechanically ventilated patients is safe provided the person performing manual ventilation knows the inspired oxygen fraction and minute ventilation required before transport and is trained to approximate them during transport.


Genetic mechanisms of hereditary hemostasis disorders.
This review summarizes known human genes whose mutations are associated with inherited hemostasis defects. These genes are divided into three groups. The genes of the first group are responsible for platelet adhesion, activation, and aggregation. The genes of the second group control the biosynthesis of blood-clotting factors and cofactors. The genes of the third group are required for the functioning of proteins involved in the anticoagulant system and fibrinolysis.


Control of the pars intermedia of the lizard, Anolis carolinensis. III. Changes in the ultrastructure of the disconnected neuro-intermediate lobe.
Morphological changes in the disconnected neuro-intermediate lobe were studied in the lizard, Anolis carolinensis from the 2nd to the 14th post-operative day using a threefold aldehyde fixative (Rodríguez, 1969). Two phases of colour change capacity were exhibited: Phase I started immediately after the transection, lasted for 6 days (mean) and was characterised by an excessive MSH release (brown skin). This phase proceeded gradually into Phase II, designated by an interruption by the MSH release (green skin). The degenerative processes and final elimination of neurons in the disconnected neural lobe propagate in a rostro-caudal direction from the transected area. The aminergic fibres (Type II) disappear within 2 days postoperatively, whereas the degeneration continues for more than 10 days in the peptidergic fibres (Type III, IV and V). The glia cells (ependyma and pituicytes) serve as very active macrophages, engulfing fragments of axons already affected by autolysis and transferring them into glial lysosomes. No apparent morphological changes occur in the shift from Phase I to II. The great majority of the secretory cells of the intermediate lobe are not affected by degenerative processes and appear to be markedly activated by the stalk transection. They exhibit numerous mitochondria, well-developed Golgi complexes forming numerous Golgi vesicles and extensive parallel cisternae of the rough endoplasmic reticulum, sometimes forming large intracisternal droplets (7 micron in diameter). Numerous pale vacuoles are seen, especially toward the intact capillaries, suggesting their coupling to the MSH release by extension of the active membrane area toward the perivascular septum. The number of these vacuoles is very markedly reduced in Phase II (no release), whereas the formation of new granules seems to proceed in early stages. The interruption of the MSH release implies a successive refilling of gradually growing secretory granules and a concomitant reduction in the development of the synthetic apparatus. Mechanisms probably involved in the control of the synthesis and release of MSH are discussed.