3DRobot: automated generation of diverse and well-packed protein structure decoys.
Computationally generated non-native protein structure conformations (or decoys) are often used for designing protein folding simulation methods and force fields. However, almost all the decoy sets currently used in literature suffer from uneven root mean square deviation (RMSD) distribution with bias to non-protein like hydrogen-bonding and compactness patterns. Meanwhile, most protein decoy sets are pre-calculated and there is a lack of methods for automated generation of high-quality decoys for any target proteins. We developed a new algorithm, 3DRobot, to create protein structure decoys by free fragment assembly with enhanced hydrogen-bonding and compactness interactions. The method was benchmarked with three widely used decoy sets from ab initio folding and comparative modeling simulations. The decoys generated by 3DRobot are shown to have significantly enhanced diversity and evenness with a continuous distribution in the RMSD space. The new energy terms introduced in 3DRobot improve the hydrogen-bonding network and compactness of decoys, which eliminates the possibility of native structure recognition by trivial potentials. Algorithms that can automatically create such diverse and well-packed non-native conformations from any protein structure should have a broad impact on the development of advanced protein force field and folding simulation methods. AVAILIABLITY AND IMPLEMENTATION: http://zhanglab.ccmb.med.umich.edu/3DRobot/ firstname.lastname@example.com; email@example.com Supplementary data are available at Bioinformatics online.


Monoclonal antibodies that recognize the type-2 activin receptor, ACTR2.
Monoclonal antibodies (MAbs) were raised in mice against a bacterial fusion protein composed of the intracellular serine/threonine kinase domain of the type-2 activin receptor, ACTR2, fused to glutathione S-transferase. Three MAbs with high affinity toward the ACTR2 kinase domain were isolated, one of which recognized specifically ACTR2 expressed transiently in vascular endothelial cells. These reagents should be of use in the elucidation of mechanisms of transmembrane signaling by this member of the emerging receptor serine threonine kinase family.


[A Case of Triple Negative Spindle Cell Carcinoma of the Breast and Improved Quality of Life Following Irinotecan Chemotherapy].
We report a case of triple negative spindle cell carcinoma of the breast, responsive to irinotecan chemotherapy. A 49-year old woman who had a tumor in the chest wall with a skin ulcer visited our hospital. After being diagnosed with triple negative spindle cell carcinoma of the breast, she underwent surgery, adjuvant chemotherapy, and radiation at the other hospital. Fourteen months after the surgery, she developed an ipsilateral breast tumor as a result of local recurrence. Since eribulin and paclitaxel plus bevacizumab chemotherapies were not effective, she was transferred to our hospital, and we administered irinotecan as third-line chemotherapy. Skin lesions and effusion were reduced and her quality of life improved for 4 months.


Nurse autonomy in cancer care.
The concept of autonomy is regarded as an essential element for gaining professional status. Yet, it remains poorly defined and understood. To date, there is little research that has focused on exploring how nurses in different specialty areas perceive autonomy. The purpose of this research was to explore oncology nurses' perceptions of autonomy and understand how they develop and exhibit autonomy in their everyday practice. Using Leininger's ethnonursing method, data were collected from 15 oncology nurses using semistructured interviews. Participant observation was also carried out through job shadowing to complement interview data. Three themes emerged from the findings: autonomy is an unspoken opportunity in the workplace; autonomy is developed through professional and personal growth acquired over time; and demonstrating autonomous behaviors is a conscious choice. The findings provide insight into how oncology nurses perceive, develop, and exhibit autonomy in everyday practice and how autonomous and collaborative clinical decision making contributes to quality cancer care. Descriptions of the meaning of autonomy and its explication in a nursing specialty practice can add to nursing knowledge by clarifying nurse autonomy and its relevance to nurses' work life. Descriptive studies can identify nurse behaviors and attitudes related to autonomy that may be measurable and relevant to real life.


The molding of intraspecific trait variation by selection under ecological inheritance.
Organisms continuously modify their environment, often impacting the fitness of future conspecifics due to ecological inheritance. When this inheritance is biased toward kin, selection favors modifications that increase the fitness of downstream individuals. How such selection shapes trait variation within populations remains poorly understood. Using mathematical modelling, we investigate the coevolution of multiple traits in a group-structured population when these traits affect the group environment, which is then bequeathed to future generations. We examine when such coevolution favors polymorphism as well as the resulting associations among traits. We find in particular that two traits become associated when one trait affects the environment while the other influences the likelihood that future kin experience this environment. To illustrate this, we model the coevolution of (a) the attack rate on a local renewable resource, which deteriorates environmental conditions, with (b) dispersal between groups, which reduces the likelihood that kin suffers from such deterioration. We show this often leads to the emergence of two highly differentiated morphs: one that readily disperses and depletes local resources, and another that maintains these resources and tends to remain philopatric. More broadly, we suggest that ecological inheritance can contribute to phenotypic diversity and lead to complex polymorphism.


[Association of fibrinogen B beta-chain gene polymorphism with factors affecting obesity].
To study the association of fibrinogen(Fg) B beta -854G/A, -455G/A, -249C/T, -148C/T, 448G/A and Bcl-1G/A gene polymorphisms with factors affecting obesity, and the fibrinogen function such as plasma fibrinogen concentration and molecular reactivity. One thousand and three hundred ninety-one subjects from Kailuan corporation were enrolled by medical examination and questionnaire survey, and were divided into normal weight, overweight and obese groups based on body mass index (BMI). Blood biochemistry, fibrinogen concentration, fibrin monomer polymerized velocity (FMPV), and FMPV/A(max) were measured. The gene polymorphisms of the six loci were detected by polymerase chain reaction-restriction fragment length polymorphism. The frequencies of Bcl-1A and its mutated genotype in the overweight group were significantly higher than that in the normal weight group (P< 0.01). In all the three groups, Fg concentration, FMPV, FMPV/A(max) in individuals with B beta -854 mutated genotype were significantly higher than those with wild type genotype (P< 0.01), and in the overweight group, FMPV/A(max) in those with B beta -455 mutated genotype, FMPV in those with B beta -249 mutated genotype, were higher than those with wild type genotype (P< 0.05). Individuals with Bcl-1A and its mutated genotype are susceptible to overweight. The B beta -455 and -249 mutated genotypes are accumulative genes for overweight by regulating the Fg function.


Diagnosis of endometriosis with imaging: a review.
Endometriosis corresponds to ectopic endometrial glands and stroma outside the uterine cavity. Clinical symptoms include dysmenorrhoea, dyspareunia, infertility, painful defecation or cyclic urinary symptoms. Pelvic ultrasound is the primary imaging modality to identify and differentiate locations to the ovary (endometriomas) and the bladder wall. Characteristic sonographic features of endometriomas are diffuse low-level internal echos, multilocularity and hyperchoic foci in the wall. Differential diagnoses include corpus luteum, teratoma, cystadenoma, fibroma, tubo-ovarian abscess and carcinoma. Repeated ultrasound is highly recommended for unilocular cysts with low-level internal echoes to differentiate functional corpus luteum from endometriomas. Posterior locations of endometriosis include utero-sacral ligaments, torus uterinus, vagina and recto-sigmoid. Sonographic and MRI features are discussed for each location. Although ultrasound is able to diagnose most locations, its limited sensitivity for posterior lesions does not allow management decision in all patients. MRI has shown high accuracies for both anterior and posterior endometriosis and enables complete lesion mapping before surgery. Posterior locations demonstrate abnormal T2-hypointense, nodules with occasional T1-hyperintense spots and are easier to identify when peristaltic inhibitors and intravenous contrast media are used. Anterior locations benefit from the possibility of MRI urography sequences within the same examination. Rare locations and possible transformation into malignancy are discussed.


In-flight medical emergencies during airline operations: a survey of physicians on the incidence, nature, and available medical equipment.
Data on the incidence of in-flight medical emergencies on-board civil aircraft are uncommon and rarely published. Such data could provide information regarding required medical equipment on-board aircraft and requisite training for cabin crew. The aim of the present study was to gather data on the incidences, nature, and medical equipment for in-flight medical emergencies by way of a survey of physician members of a German aerospace medical society. Using unipark.de (QuestBack GmbH, Cologne, Germany), an online survey was developed and used to gather specific information. Members of the German Society for Aviation and Space Medicine (Deutsche Gesellschaft für Luft- und Raumfahrtmedizin e.V.; DGLRM) were invited to participate in the survey during a 4-week period (21 March 2015 to 20 April 2015). Chi-square test was used for statistical analysis (p<0.05 was considered significant). Altogether, 121 members of the society responded to the survey (n=335 sent out). Of the 121 respondents, n=54 (44.6%) of the participants (89.9% male and 10.1% female; mean age, 54.1 years; n=121) were involved in at least one in-flight medical emergency. Demographic parameters in this survey were in concordance with the society members' demographics. The mean duration of flights was 5.7 hours and the respondents performed 7.1 airline flights per year (median). Cardiovascular (40.0%) and neurological disorders (17.8%) were the most frequent diagnoses. The medical equipment (78.7%) provided was sufficient. An emergency diversion was undertaken in 10.6% of the cases. Although using a different method of data acquisition, this survey confirms previous data on the nature of emergencies and gives plausible numbers. Our data strongly argue for the establishment of a standardized database for recording the incidence and nature of in-flight medical emergencies. Such a database could inform on required medical equipment and cabin crew training.


High-fidelity de novo synthesis of pathways using microchip-synthesized oligonucleotides and general molecular biology equipment.
Engineering and evaluation of synthetic routes for generating valuable compounds require accurate and cost-effective de novo synthesis of genetic pathways. Here, we present an economical and streamlined de novo DNA synthesis approach for engineering a synthetic pathway with microchip-synthesized oligonucleotides (oligo). The process integrates entire oligo pool amplification, error-removal, and assembly of long DNA molecules. We utilized this method to construct a functional lycopene biosynthetic pathway (11.9 kb encoding 10 genes) in Escherichia coli using a highly error-prone microchip-synthesized oligo pool (479 oligos) without pre-purification, and the error-frequency was reduced from 14.25/kb to 0.53/kb. This low-equipment-dependent and cost-effective method can be widely applied for rapid synthesis of biosynthetic pathways in general molecular biology laboratories.


Age-Related Changes in Post-Translational Modifications of Proteins from Whole Male and Female Skeletal Elements.
One of the key questions in forensic cases relates to some form of age inference, whether this is how old a crime scene is, when in time a particular crime was committed, or how old the victim was at the time of the crime. These age-related estimations are currently achieved through morphological methods with varying degrees of accuracy. As a result, biomolecular approaches are considered of great interest, with the relative abundances of several protein markers already recognized for their potential forensic significance; however, one of the greatest advantages of proteomic investigations over genomics ones is the wide range of post-translational modifications (PTMs) that make for a complex but highly dynamic resource of information. Here, we explore the abundance of several PTMs including the glycosylation, deamidation, and oxidation of several key proteins (collagen, fetuin A, biglycan, serum albumin, fibronectin and osteopontin) as being of potential value to the development of an age estimation tool worthy of further evaluation in forensic contexts. We find that glycosylations lowered into adulthood but deamidation and oxidation increased in the same age range.


[Study on the interaction of Et2SnCl2(phen) with DNA].
The absorbance, fluorescence and cyclic voltammetric methods as well as agarose gel electrophoresis were used to study the interaction of the antitumor compound Et2SnCl2(phen) with DNA. The results indicate that Et2SnCl2 (phen) mainly reacts electrostatically with the phosphate backbone of DNA. There also exists an intercalation into the double-helix of DNA through the phenanthroline group of Et2SnCl2(phen). At high concentration Et2SnCl2(phen) can cause unwinding of DNA. The molecular action mechanism of Et2SnCl2(phen) with DNA was first proposed.


Markers of oxidative injury in the cerebrospinal fluid of a premature infant with meningitis and periventricular leukomalacia.
Free radicals have been hypothesized to play a key role in the evolution of periventricular leukomalacia, although direct evidence of oxidative injury in the human infant is lacking. This case report is the first to demonstrate a marked elevation in the levels of lipid and protein oxidative products in the cerebrospinal fluid during the evolution of periventricular leukomalacia in a premature infant with meningitis.


A retrospective study of 60 cases of salivary gland tumors in a Thai population.
Sixty cases of salivary gland tumors were diagnosed in the Oral Pathology Department, Faculty of Dentistry, Mahidol University, Bangkok, Thailand, from 1973 to 2002. Fifty-two cases (86.7%) involved the intraoral minor salivary glands, six cases (10%) were found in the major glands, and two cases (3.3%) were intrabony. The predominance of malignant over benign tumors was evident with 68.3% being malignant and 31.7% benign. Patients ranged in age from 9 to 75 years. The female to male ratio of benign intraoral salivary gland tumors was 1.4 to 1 and of malignant types was 1.1 to 1. The principle site of occurrence was the palate (65.4%), followed by buccal mucosa (13.5%). Pleomorphic adenoma (30%) was the most common benign tumor, and mucoepidermoid carcinoma (44.3%) was the most common malignant tumor. Comparing the data from the present study with other series, some discrepancies exist.


Urinary neutrophil gelatinase-associated lipocalin rapidly decreases in the first week after kidney transplantation.
Recipient delayed graft function, which is defined as dialysis in the first week after transplantation, is one of the most common early complications after kidney transplantation. This study aimed to evaluate the daily changes in renal function-related biomarkers in the first week post-transplant. A total of 72 kidney transplant recipients were retrospectively included in this study. Clinical and laboratory data were collected daily during the first week post-transplant, including urinary concentrations of neutrophil gelatinase-associated lipocalin (NGAL), serum concentrations of NGAL, creatinine, urea nitrogen, uric acid (UA), β2-microglobulin, cystatin C, and estimated glomerular filtration rate (eGFR). There were no significant differences in urea nitrogen (P = .375), UA (P = .090), and cystatin C (P = .691), while urinary NGAL (P < .0001), serum NGAL (P < .0001), creatinine (P < .0001), β2-microglobulin (P < .0001), and eGFR (P < .0001) were statistically significant in the first week post-transplant. In comparison with serum NGAL (P < .0001), creatinine (P < .0001), β2-microglobulin (P = .001), and eGFR (P = .001), the change ratios of urinary NGAL changed the most between day 1 and day 2 after renal transplantation, while the changing degree of urinary NGAL showed no significant difference compared with these indicators between day 1 and day 7 after kidney transplantation. Urinary NGAL is a sensitive marker for indicating renal function. Urinary NGAL combined with other markers can be more helpful for evaluating renal function in the first week following kidney transplantation.


How many founders for a biological invasion? Predicting introduction outcomes from propagule pressure.
Ecological theory on biological invasions attempts to characterize the predictors of invasion success and the relative importance of the different drivers of population establishment. An outstanding question is how propagule pressure determines the probability of population establishment, where propagule pressure is the number of individuals of a species introduced into a specific location (propagule size) and their frequency of introduction (propagule number). Here, we used large-scale replicated mesocosm ponds over three reproductive seasons to identify how propagule size and number predict the probability of establishment of one of world's most invasive fish, Pseudorasbora parva, as well as its effect on the somatic growth of individuals during establishment. We demonstrated that, although a threshold of 11 introduced pairs of fish (a pair is 1 male, 1 female) was required for establishment probability to exceed 95%, establishment also occurred at low propagule size (1-5 pairs). Although single introduction events were as effective as multiple events at enabling establishment, the propagule sizes used in the multiple introductions were above the detected threshold for establishment. After three reproductive seasons, population abundance was also a function of propagule size, with rapid increases in abundance only apparent when propagule size exceeded 25 pairs. This was initially assisted by adapted biological traits, including rapid individual somatic growth that helped to overcome demographic bottlenecks.


Potential Opportunities for Prevention or Earlier Diagnosis of Child Physical Abuse in the Inpatient Setting.
To compare rates of previous inpatient visits among children hospitalized with child physical abuse (CPA) with controls as well as between individual abuse types. In this study, we used the Pediatric Health Information System administrative database of 44 children's hospitals. Children <6 years of age hospitalized with CPA between January 1, 2011, and September 30, 2015, were identified by discharge codes and propensity matched to accidental injury controls. Rates for previous visit types were calculated per 10 000 months of life. χ2 and Poisson regression were used to compare proportions and rates. There were 5425 children hospitalized for CPA. Of abuse and accident cases, 13.1% and 13.2% had a previous inpatient visit, respectively. At previous visits, abused children had higher rates of fractures (rate ratio [RR] = 3.0 times; P = .018), head injuries (RR = 3.5 times; P = .005), symptoms concerning for occult abusive head trauma (AHT) (eg, isolated vomiting, seizures, brief resolved unexplained events) (RR = 1.4 times; P = .054), and perinatal conditions (eg, prematurity) (RR = 1.3 times; P = .014) compared with controls. Head injuries and symptoms concerning for occult AHT also more frequently preceded cases of AHT compared with other types of abuse (both P < .001). Infants hospitalized with perinatal-related conditions, symptoms concerning for occult AHT, and injuries are inpatient populations who may benefit from abuse prevention efforts and/or risk assessments. Head injuries and symptoms concerning for occult AHT (eg, isolated vomiting, seizures, and brief resolved unexplained events) may represent missed opportunities to diagnose AHT in the inpatient setting; however, this requires further study.


Effects of glucagon-like peptide 1 (7-36 amide) on glucose kinetics during somatostatin-induced suppression of insulin secretion in healthy men.
Glucagon-like peptide 1 (GLP-1) is known to stimulate insulin secretion and biosynthesis, but has also been shown to decrease insulin requirements in type 1 diabetic subjects suggesting insulin-independent effects. To assess whether GLP-1 exerts also direct effects on whole-body glucose metabolism, 6,6-D2-glucose kinetics were measured in 8 healthy volunteers receiving once GLP-1, once saline during hyperglycemic glucose clamping, while somatostatin with replacement amounts of insulin, glucagon and growth hormone was infused. Even though endogenous insulin secretion could not be blocked completely (increased plasma concentrations of C-peptide and proinsulin), somatostatin infusion resulted in stable insulin and glucagon plasma levels in both protocols (GLP-1 vs. placebo: NS). After 3 h of GLP-1 infusion, peripheral glucose disappearance significantly increased compared to placebo (p < 0.03) despite of somatostatin-induced suppression of insulin and glucagon secretion. Thus, GLP-1 infusion seems to have direct stimulatory effects on peripheral glucose metabolism in man.


The impact of affective temperaments on clinical and functional outcome of Bipolar I patients that initiated or changed pharmacological treatment for mania.
Affective temperaments have been shown to impact on the clinical manifestations and the course of bipolar disorder. We investigated their influence on clinical features and functional outcome of manic episode. In a naturalistic, multicenter, national study, a sample of 194 BD I patients that initated or changed pharmacological treatment for DSM-IV-TR manic episode underwent a comprehensive evaluation including briefTEMPS-M, CTQ, YMRS, MADRS, FAST, and CGI-BP. Factorial, correlation and comparative analyses were conducted on different temperamental subtypes. Depressive, cyclothymic, irritable and anxious temperaments resulted significantly correlated with each other. On the contrary, hyperthymic temperament scores were not correlated with the other temperamental dimensions. The factorial analysis of the briefTEMPS-M sub-scales total scores allowed the extraction of two factors: the Cyclothymic-Depressive-Anxious (Cyclo-Dep-Anx) and the Hyperthymic. At final evaluation Dominant Cyclo-Dep-Anx patients reported higer scores in MADRS and in CTQ emotional neglect and abuse subscale scores than Dominant Hyperthymic patients. The latter showed a greater functional outcome than Cyclo-Dep-Anx patients. Affective temperaments seem to influence the course of mania. Childhood emotional abuse and neglect were related to the cyclothymic disposition. Cyclothymic subjects showed more residual depressive symptoms and Hyperthymic temperament is associated with a better short-term functional outcome.


Improved glucose control in nonhospitalized pregnant diabetic patients.
Methods for management of diabetic pregnancy in the outpatient setting require strict glucose control. To assess the effect of diet and injection of short and intermediate acting insulin on glucose, diabetic patients tested their urine daily for glucose and had biweekly serum glucose tests. A brief metabolic ward study in 9 diabetic patients during the third trimester yielded hourly glucose determinations. These results defined the range of serum glucose over a 24-hour period. Glucose data on 6 normal third trimester women also came from hourly glucose values. Glucose results of normal and diabetic subjects were similar. A 16th subject with diabetic eye, renal, and foot complications is included as a case report to illustrate management technics. Infants of the diabetic women had no perinatal mortality, morbidity, or macrosomia and thus differ from an earlier study where glucose was not strictly controlled. The data suggest hospitalization can be short and low perinatal morbidity and mortality are possible with this outpatient method of management of the pregnant diabetic patient.


Patterns of presentation and mortality in tetanus: a 10-year retrospective review.
To highlight the indications, problems and prospects of bedside non-surgically inserted jugular and subclavian dual luman catheters. Renal failure patients being managed in our centre with indications for central catheterisation were consecutively recruited at presentation. They had bedside non-surgical jugular and subclavian insertion using modified seldinger wire technique and the performance of the Gatheters monitored. Sixteen patients aged between 23 and 65 years had 32 central catheterisations during the 12-month period. The indications included its use as haemodialysis access in all patients, additional indications were CVP monitoring in 5, and parenteral hyperalimentation in 1. Three catheterisations were in right subclavian vein, 4 in let internal jugular vein and 25 in right internal jugular vein. The duration of use ranged between 3 days and 11 weeks and blood flow rate used ranged between 50 and 350ml/min. Nine (28.1%) catheterisations were complicated with exit site and systemic infection. Catheter blockage and accidental catheter removal were recorded in 3 patients each. Carotid artery puncture was recorded in 2 patients but haemostasis was maintained with direct digital compression. We conclude that percutaneous bedside internal jugular and subclavian (venous) catheterisation using dual lumen catheter is safe and devoid of major complications. Tetanus, an ubiquitous disease still ravages our population despite the fact that it is totally preventable. The mortality had remained high with its attendant socio-economic implications as it affects mainly farmers in their prime of life. We conducted this retrospective review to be able to determine pattern of presentation, case fatality rate and factors influencing mortality with a view to mapping out control strategies. The case records of all managed patients aged 16 and above over a ten-year period (1992-2001) were retrieved and socio-demographic and clinical data as well as results of laboratory investigations were collated. Analysis was done using SPSS package. Chi-square analysis and student t-test were used for comparison of means as appropriate. P-values of <0. 05 was taken as significant. There were a total of 114 patients managed during the period, which comprised of 85 males and 29 females. The means age (+/- SD) was 35.96 (+/-17.76). Sixty six (57.89%) patients are either jobless or farmers. Majority of the patients had injuries in the lower limb 59.65% when compared with 20.18% that had theirs in the upper limb. 107 (93.86%) of the patients presented with trismus while only 82 (71.93%) had opsthotonus. Only 51 (44.73%) patients survived while 61 (53.5%) died. The mean age (+/- SD) of the survivors was 32.35 (+ 14.45) years while that of those that died was 39.4 (+/- 19.89) years (P = 0.036). Other factors that significantly influenced survival included severity of spasms (P = 0/003), tachycardia (P = 0.044), and degree of sedation (P <0.0001). No association was found between survival and incubation period, period of onset, site of injury and associated medical conditions. Tetanus is still associated with high mortality rate. Factors such as severity of spasma, age, sedation and tachycardia were found to significantly influence mortality. It is recommended that prophylactic life immunisation against tetanus be given to all Nigerians.


Better Ask Than Tell: Responses to mHealth Interrogative Reminders and Associations With Colorectal Cancer Screening Subsequent Uptake in a Prospective Cohort Intervention.
Text message (short message service, SMS) interrogative reminders were adopted in population screening for the early detection of colorectal cancer (CRC). This study aims to examine responses to text message (SMS) reminders and associate responses with senders' characteristics, message type (interrogative/declarative), and subsequent screening uptake. We conducted a prospective cohort intervention. Text message (SMS) reminders to undergo CRC screening, randomized into interrogative and declarative phrasing, were sent to nonadherent 40,000 women and men (age 50-74 years) at CRC average risk. We analyzed recipient responses by message phrasing, recipient characteristics, and for content, the latter predicting subsequent CRC screening per program database. While interrogative text message (SMS) reminders elicited 7.67% (1475/19,227) responses, declarative ones elicited 0.76% (146/19,262) responses. Text message (SMS) responses were content analyzed and grouped into attitudes toward CRC screening (1237/1512, 81.8% positive) and intention to screen (1004/1512, 62.6%). Text message (SMS) respondents screened significantly more than nonrespondents after 6 months (415/1621, 25.6% vs 3322/36,868, 9.0%; χ12=487.5, P<.001); 1 year (340/1621, 21.0% vs 4711/36,868; χ12=91.5, P<.001); and 2 years (225/1621, 13.9% vs 3924/36,868; χ12=16.9, P<.001) following the reminders. In a multivariable logistic regression among text message (SMS) respondents, screening after 6 months was significantly predicted by older age, past sporadic screening, attitudes, and intentions. Interrogative text message (SMS) reminders reached previously uninvolved sectors in the CRC target population-men, sporadic-screenees, and the "never-tested" before. This novel application resulted in a population-level, incrementally enhanced screening. Asking patients about their future health behavior may be relevant for enhancing other health behaviors in preventive medicine and clinical settings.


[Recurrent hemangioendothelioma of the lower and middle segments of inferior vena cava with spread to previously installed prosthesis].
We report surgical treatment of a 65-year-old patient with recurrent hemangioendothelioma of inferior and middle segment of inferior vena cava with spread to previously established prosthesis. Advanced resection of inferior vena cava and right-sided nephrectomy were not followed by complications and resulted R0 resection. Surgery time was 180 min. Inferior vena cava cross-clamping time was 30 min. Total blood loss was 300 ml. Hemangioendothelioma is a rare tumor with unpredictable potential for malignant transformation and obligatory indications for surgical treatment. Resection and reconstruction of inferior vena cava and renal veins with a synthetic conduit is effective and safe procedure.


Taste Receptor Polymorphisms and Immune Response: A Review of Receptor Genotypic-Phenotypic Variations and Their Relevance to Chronic Rhinosinusitis.
Bitter (T2R) and sweet taste (T1R) receptors have emerged as regulators of upper airway immune responses. Genetic variation of these taste receptors additionally confers susceptibility to infection and has been implicated in severity of disease in chronic rhinosinusitis (CRS). Ongoing taste receptor research has identified a variety of biologically active compounds that activate T1R and T2R receptors, increasing our understanding of not only additional receptor isoforms and their function but also how receptor function may contribute to the pathophysiology of CRS. This review will discuss the function of taste receptors in mediating airway immunity with a focus on recently described modulators of receptor function and directions for future research into the potential role of genotypic and phenotypic receptor variation as a predictor of airway disease and response to therapy.


Light-driven liquid metal nanotransformers for biomedical theranostics.
Room temperature liquid metals (LMs) represent a class of emerging multifunctional materials with attractive novel properties. Here, we show that photopolymerized LMs present a unique nanoscale capsule structure characterized by high water dispersibility and low toxicity. We also demonstrate that the LM nanocapsule generates heat and reactive oxygen species under biologically neutral near-infrared (NIR) laser irradiation. Concomitantly, NIR laser exposure induces a transformation in LM shape, destruction of the nanocapsules, contactless controlled release of the loaded drugs, optical manipulations of a microfluidic blood vessel model and spatiotemporal targeted marking for X-ray-enhanced imaging in biological organs and a living mouse. By exploiting the physicochemical properties of LMs, we achieve effective cancer cell elimination and control of intercellular calcium ion flux. In addition, LMs display a photoacoustic effect in living animals during NIR laser treatment, making this system a powerful tool for bioimaging.


Pharmacokinetic analysis of enterohepatic circulation of etodolac and effect of hepatic and renal injury on the pharmacokinetics.
This study was designed to evaluate the enterohepatic circulation of racemic etodolac in rats. Additionally, the effect of hepatic and renal failure on the pharmacokinetics was estimated. The biliary excretion and the reabsorption of the drug excreted in bile were examined in order to clarify the effect of enterohepatic circulation on the disposition, and a pharmacokinetics model was applied to describe the enterohepatic circulation. The relatively rapid elimination of etodolac was seen in the bile-exteriorized rats (BE rat) compared with that in control rats. Total biliary excretion of etodolac, mainly as glucuronides, after intravenous administration was about 45% of the dose, indicating extensive enterohepatic circulation of the drug. The plasma concentrations of the drug in bile duct-linked rats approximately agreed with the simulation curve by the model, with the peak concentration 6-7 h after dosing. The elimination of the drug was markedly retarded in rats with hepatic (CCI4-induced) and renal (uranyl acetate-induced) failure, and high plasma levels were maintained over the longer times, due to greatly decreased distribution volume. The biliary excretion of etodolac enantiomers was not significantly different between the control and CCI4-groups, suggesting that hepatic glucuronyl transferase activity was preserved in rats impaired by CCI4.


Determinants of hyperkyphosis in patients with ankylosing spondylitis.
To determine clinical and radiographic determinants of hyperkyphosis in patients with ankylosing spondylitis. Spinal hyperkyphosis was assessed by occiput to wall distance (OWD) in 135 patients participating in the OASIS cohort and defined as OWD >0. Disease activity was assessed by the Bath ankylosing spondylitis disease activity index (BASDAI). Wedging of the vertebrae was calculated as the Ha/Hp ratio. Structural damage of the spine was assessed by the modified Stoke ankylosing spondylitis spine score (mSASSS). Hip involvement was assessed by the Bath ankylosing spondylitis radiology index (BASRI) and defined as a score >2. Data were analysed by multiple regression analysis on van der Waerden-normal OWD values, with mean Ha/Hp ratio, mSASSS, hip involvement, and BASDAI as explanatory variables, and age, sex, and disease duration after diagnosis as covariates. 61 patients (45.2%) had an OWD >0 cm. Of these, 81% were male, v 57% in the group with normal OWD (p<0.001). Forty two patients had wedged thoracic vertebrae, and 27 of these (44%) had an increased OWD, compared with 15 of 74 with a normal OWD (20%) (p = 0.005). OWD was correlated with mean wedging of the thoracic spine (r = -0.45, p = 0.01), mSASSS (r = 0.56, p = 0.01), and hip involvement (r = 0.2, p = 0.05). Multivariate analysis showed that mSASSS (standardised beta (stbeta) = 0.52; p<0.001), wedging of the thoracic spine (stbeta = -0.28; p = 0.01), and BASDAI (stbeta = 0.15; p = 0.05) were independent determinants of OWD. Radiological damage of the cervical and lumbar spine, thoracic wedging, and disease activity are determinants of hyperkyphosis in patients with ankylosing spondylitis. These findings could be important in determining treatment goals in this disease.


Thy 1+ donor cells that promote allograft tolerance in sublethally irradiated MHC-disparate hosts.
We have previously demonstrated that depletion of Thy 1+ cells impairs the capacity of C57BL/6J, H-2b bone marrow cells, BMC, and BALB/cxC57BL/6J F1 BMC and spleen cells (SC) to establish mixed lymphoid chimerism and tolerance for donor-specific skin grafts in sublethally irradiated (240 cGy x3) BALB/c, H-2d hosts. In the present studies incubation with anti Ly2.2 + C markedly reduced the capacity of BALB/cxC57BL/6J, F1 SC to induce tolerance and chimerism (P less than .001). Incubation with anti-L3T4 + C had an inhibitory effect of borderline significance (P less than .04). Incubation with L-leucyl-L-leucine methyl ester (which removes NK cells, Tc, and precursor Tc) had no effect on the capacity of either C57BL/6J BMC or BALB/cxC57BL/6J F1 BMC or SC to establish chimerism and induce skin graft tolerance. These results suggest that tolerance-promoting Thy 1+ cells are not cytotoxic T cells. Both Ly2+ noncytotoxic CD8+ and L3T4+ noncytotoxic CD4+ cells may be involved. Alternatively the requisite Thy 1+ cells may be immature T cells that express both Ly2 and L3T4.


Extroversion, social support and life satisfaction in old age: a mediation model.
The aim of this study was twofold: on the one hand to analyze whether extroversion predicts social support in older people, and on the other hand to determine if different types of social support mediate the effect that extroversion has on older people's life satisfaction. The sample comprised 406 community-dwelling older adults (M = 74.88, SD = 6.75) from urban areas of Granada, southern Spain. Extroversion was positively correlated with emotional (r = .23) and with affectionate support (r = .30). Extroversion and all types of social support also positively correlated with life satisfaction. The multiple mediation analysis revealed that when age, gender, marital status and loneliness were controlled, extroversion predicted emotional (B = .008, p < .01) and affectionate support (B = .015, p < .01) and emotional and affectionate support mediated the association between extroversion and life satisfaction (total effect: B = .034, SE = .0024, p < .001, r2 = .295). Results from this study highlight the fact supportive social relations are crucial for older people's life satisfaction. Also emotional and affectionate support constitutes important explanatory mechanisms of the indirect effect of extroversion on life satisfaction. Personality traits should be considered when interventions aimed at promoting life satisfaction in old age and successful aging are designed.


Endovascular management of distal anterior inferior cerebellar artery aneurysms: Report of two cases and review of the literature.
Aneurysms of the anterior inferior cerebellar artery (AICA), especially those located in the distal portion of the AICA, are rare. There are few reported cases treated with surgery or endovascular embolization. We report two cases of fusiform distal AICA aneurysms presenting with subarachnoid hemorrhage. Parent artery occlusion with coils and n-butyl cyanoacrilate (n-BCA) resulted in complete aneurysm occlusion and prevented rebleeding. Both patients presented postprocedure neurological deficits, but have made a good recovery at 4 and 10 months, respectively. Occlusion of the parent artery for the treatment of ruptured fusiform distal AICA aneurysms is effective but has significant neurological risks.


[Effect of EA on the enzymes of microvasculature and CA fluorescence in acute myocardial ischemia].
It was aimed at observing the histochemical basis of physiological experiment about the effect of electroacupuncture (EA) on acute myocardial ischemia (AMI) in this paper. The capillaries of myocardium were reflected with both alkaline phosphatase (ALP) and Mg(2+)-ATPase. Thirty min after ligating the left ventricular branch (LVB), the capillaries stained by ALP were much decreased in the ischemic group without EA, while in EA group they were increased distinctly. The number and the total length of the capillaries in a 220 x 320 microns ischemic area of the posterior wall (section 10 microns) were measured and compared. In ischemic group the number was 17.2 +/- 1.65, the length was 634.62 +/- 66.24 microns, in EA group 22.5 +/- 1.44, 1187.57 +/- 103.69 microns, respectively. Both counts were significant differences (P < 0.05, P < 0.001). It reflected that EA could improve the microcirculation and metabolic function of AMI. Mg(2+)-ATPase was shown on the plasma membrane of endothelial cell of microvasculature and analysed quantitatively with a Univar scanning microspectrophotometer. After occluding LVB for 30 min its optic density of AMI was decreased to 106.83 +/- 14.06, while it was increased to 210.83 +/- 24.88 in EA group, P < 0.05. The activity of Mg(2+)-ATPase could increase in transporting Na+, k+ ions through the membrane of the endothelial cells of ischemic myocardium. The result was consistent with the physiological experiment, because EA could regulate the changes of mean repolarization rate induced by AMI and adjust the ion concentration of transmembrane. The catecholamine (CA) in myocardium was located at sympathetic adrenergic terminals with varicosities containing norepinephrine (NE).(ABSTRACT TRUNCATED AT 250 WORDS)


Mammalian cells contain a second nucleocytoplasmic hexosaminidase.
Some thirty years ago, work on mammalian tissues suggested the presence of two cytosolic hexosaminidases in mammalian cells; one of these has been more recently characterized in a recombinant form and has an important role in cellular function due to its ability to cleave beta-N-acetylglucosamine residues from a variety of nuclear and cytoplasmic proteins. However, the molecular nature of the second cytosolic hexosaminidase, named hexosaminidase D, has remained obscure. In the present study, we molecularly characterize for the first time the human and murine recombinant forms of enzymes, encoded by HEXDC genes, which appear to correspond to hexosaminidase D in terms of substrate specificity, pH dependency and temperature stability. Furthermore, a Myc-tagged form of this novel hexosaminidase displays a nucleocytoplasmic localization. Transcripts of the corresponding gene are expressed in a number of murine tissues. On the basis of its sequence, this enzyme represents, along with the lysosomal hexosaminidase subunits encoded by the HEXA and HEXB genes, the third class 20 glycosidase to be identified from mammalian sources.


Identification of candidate diagnostic serum biomarkers for Kawasaki disease using proteomic analysis.
Kawasaki disease (KD) is a systemic vasculitis and childhood febrile disease that can lead to cardiovascular complications. The diagnosis of KD depends on its clinical features, and thus it is sometimes difficult to make a definitive diagnosis. In order to identify diagnostic serum biomarkers for KD, we explored serum KD-related proteins, which differentially expressed during the acute and recovery phases of two patients by mass spectrometry (MS). We identified a total of 1,879 proteins by MS-based proteomic analysis. The levels of three of these proteins, namely lipopolysaccharide-binding protein (LBP), leucine-rich alpha-2-glycoprotein (LRG1), and angiotensinogen (AGT), were higher in acute phase patients. In contrast, the level of retinol-binding protein 4 (RBP4) was decreased. To confirm the usefulness of these proteins as biomarkers, we analyzed a total of 270 samples, including those collected from 55 patients with acute phase KD, by using western blot analysis and microarray enzyme-linked immunosorbent assays (ELISAs). Over the course of this experiment, we determined that the expression level of these proteins changes specifically in the acute phase of KD, rather than the recovery phase of KD or other febrile illness. Thus, LRG1 could be used as biomarkers to facilitate KD diagnosis based on clinical features.


A thermal porosimetry method to estimate pore size distribution in highly porous insulating materials.
Standard pore size determination methods such as mercury porosimetry, nitrogen sorption, microscopy, or x-ray tomography are not always applicable to highly porous, low density, and thus very fragile materials. For this kind of materials, a method based on thermal characterization is proposed. Indeed, the thermal conductivity of a highly porous and insulating medium is significantly dependent on the thermal conductivity of the interstitial gas that depends on both gas pressure and size of the considered pore (Knudsen effect). It is also possible to link the pore size with the thermal conductivity of the medium. Thermal conductivity measurements are realized on specimens placed in an enclosure where the air pressure is successively set to different values varying from 10(-1) to 10(5) Pa. Knowing the global porosity ratio, an effective thermal conductivity model for a two-phase air-solid material based on a combined serial-parallel model is established. Pore size distribution can be identified by minimizing the sum of the quadratic differences between measured values and modeled ones. The results of the estimation process are the volume fractions of the chosen ranges of pore size. In order to validate the method, measurements done on insulating materials are presented. The results are discussed and show that pore size distribution estimated by the proposed method is coherent.


Aberrant Huntingtin interacting protein 1 in lymphoid malignancies.
Huntingtin interacting protein 1 (HIP1) is an inositol lipid, clathrin, and actin binding protein that is overexpressed in a variety of epithelial malignancies. Here, we report for the first time that HIP1 is elevated in non-Hodgkin's and Hodgkin's lymphomas and that patients with lymphoid malignancies frequently had anti-HIP1 antibodies in their serum. Moreover, p53-deficient mice with B-cell lymphomas were 13 times more likely to have anti-HIP1 antibodies in their serum than control mice. Furthermore, transgenic overexpression of HIP1 was associated with the development of lymphoid neoplasms. The HIP1 protein was induced by activation of the nuclear factor-kappaB pathway, which is frequently activated in lymphoid malignancies. These data identify HIP1 as a new marker of lymphoid malignancies that contributes to the transformation of lymphoid cells in vivo.


Asymptomatic malposition of a pacing lead in the left ventricle: the case of a woman untreated with anticoagulant therapy for eight years.
We report the case of a woman with a low-rate atrial fibrillation and a wire lead inadvertently inserted in the left ventricle through an ostium secundum defect. The malposition of the lead was diagnosed 8 years after the procedure on the basis of the presence of a right bundle branch block pattern of the paced QRS, at echocardiography and at chest X-ray. The patient, who was neither on antiaggregant nor anticoagulant therapy, was asymptomatic. Biventricular pacing is a useful tool in the therapy of patients with severe chronic heart failure and intraventricular conduction delay but the insertion of the lead in the left ventricle through the coronary sinus is not always feasible. Because a patent foramen ovale is a frequent occurrence in the adult population, we suggest that in case of an unsuccessful catheterization of the coronary sinus, the physician should search for a patent foramen ovale through which to introduce the wire lead into the left ventricle, especially if the patient is already receiving anticoagulant therapy.


[Y chromosome variations and hyplogroups from 15 biallelic markers in six Chinese populations].
By using 15 biallelic markers, 342 male individuals from six populations in China were genotyped with ASPCR (allele specific PCR). The 15 biallelic markers included M1 (YAP), M15 (9 bp insertion), M89 (C-->T), M9 (C-->G), M119 (A-->C), M50 (T-->C), M110 (T-->C), M103 (C-->T), M95 (C-->T), M88 (A-->G), M111 (2-bp deletion), M45 (G-->A), M122 (T-->C), M7 (C-->G) and M134 (1 bp deletion). The distribution of variation frequencies of 15 biallelic markers in six populations showed that with the extremely high frequencies of M9G (96.20% & 96.43%) and Han nationality displayed higher diversity than the four minority populations. It's noteworthy that M95T (82.14%) in Sichuan Han and M45A (18.57%) in Hui gave prominace to the two populations. The six populations displayed 34 (Fujian Han), 21 (Sichuan Han), 14 (Mongol), 26 (Hui), 10 (Xibo) and 8 (Hezhe) haplogroups respectively with 2, 1, 2, 1, 2 and 2 prominent haplogroups among them. Furthermore, the haplogroup analysis revealed that one predominant haplogroup was shared in the four minority populations and even two predominant haplogroups were shared in Mongol, Hezhe and Xibo. Unlike Han populations, the minority populations showed strikingly different haplogroups which were close to the ancestral pattern. However, the two Han populations exhibited divergence between them with the distinct frequencies of M89T and M95T. With the comparison of the number of people sharing the common haplogroups between any two of the four minority populations, relative genetic distance among them was deduced.


The revised critical thinking skills scale for a life-and-death course: preliminary scale refinement.
Death education involves acquiring knowledge, changing behavior, and developing proper views of life in both the affective and the value domains. Critical thinking that is honed through reflecting on life-and-death issues represents a way to reach these goals. Designing assessments able to measure college student content and critical thinking skills related to life-and-death issues is thus important. The Test of Critical Thinking Skills for Life-And-Death content (TCTS-LD) instrument requires the administration of additional tests to assess reliability and validity for future use in the assessment of perceptions on life and death. The purpose of this study was to refine the TCTS-LD. A cross-sectional, descriptive design was used to recruit 715 college students in southern Taiwan. Three structured scales were administered in class to the participants. Data were collected in 2004 and 2006. Confirmatory factor analysis was applied to validate the structure of scales. Examination of the reliability of the three-factor and 15-item scale revealed a Kuder-Richardson coefficient of internal consistency of .54. The split-half reliability coefficients were .47 in the Spearman-Brown correlation and .40 in the intraclass correlation coefficient (ICC). The test-retest reliability coefficients (n = 22) were .58 in Pearson correlation and .56 in ICC. In addition to content validity verification by experts and face validity by students, the validity of this test was assessed using three methods, including (a) a comparable validity rating between this test and the TCTS-A (r = .34, p < .001; (b) a contrast-group technique with different responses to the instrument between those in education and nursing majors (t = 2.71, p < .01), with scores of 10.98 (SD = 2.42) and 9.82 (SD = 2.25), respectively; and (c) a confirmatory factor analysis confirming that TCTS-LD is related to the three dimensions of assumption, evaluation, and induction (χ = 81.800, p = .158, normed chi-square χ/df = 1.169, comparative fit index [CFI] = .976, Tucker-Lewis index = .984, root mean square error of approximation [RMSEA] = 0.015). Three factors explained 31.19% of total variance for the revised TCTS-LD. The revised TCTS-LD scale improved performance and effectiveness to a certain degree. However, reliability and construct validity must be further tested to permit its use as an evaluation tool.


A new MAGDM method with 2-tuple linguistic bipolar fuzzy Heronian mean operators.
In this article, we introduce the 2-tuple linguistic bipolar fuzzy set (2TLBFS), a new strategy for dealing with uncertainty that incorporates a 2-tuple linguistic term into bipolar fuzzy set. The 2TLBFS is a better way to deal with uncertain and imprecise information in the decision-making environment. We elaborate the operational rules, based on which, the 2-tuple linguistic bipolar fuzzy weighted averaging (2TLBFWA) operator and the 2-tuple linguistic bipolar fuzzy weighted geometric (2TLBFWG) operator are presented to fuse the 2TLBF numbers (2TLBFNs). The Heronian mean (HM) operator, which can reflect the internal correlation between attributes and their influence on decision results, is integrated into the 2TLBF environment to analyze the effect of the correlation between decision factors on decision results. Initially, the generalized 2-tuple linguistic bipolar fuzzy Heronian mean (G2TLBFHM) operator and generalized 2-tuple linguistic bipolar fuzzy weighted Heronian mean (G2TLBFWHM) operator are proposed and properties are explained. Further, 2-tuple linguistic bipolar fuzzy geometric Heronian mean (2TLBFGHM) operator and 2-tuple linguistic bipolar weighted geometric Heronian mean (2TLBFWGHM) operator are proposed along with some of their desirable properties. Then, an approach to multi-attribute group decision-making (MAGDM) based on the proposed aggregation operators under the 2TLBF framework is developed. At last, a numerical illustration is provided for the selection of the best photovoltaic cell to demonstrate the use of the generated technique and exhibit its adequacy.


Health impact and related cost of ambient air pollution in Tehran.
Ambient air pollution represents one of the biggest environmental risks to health. In this study, we estimated the avoidable mortality burden attributable to ambient air pollution in Tehran, and derived the economic impact associated with these health effects. Using PM2.5 data from ground-level air pollution measurements in Tehran, we estimated PM2.5 exposure for 349 neighborhoods in Tehran, by the Environmental Benefits Mapping and Analysis Program (BenMAP-CE). We considered five scenarios related to PM2.5 levels: an increase to 35 μg/m3; a reduction to 25 μg/m3; a reduction to 15 μg/m3; a reduction to 10 μg/m3 (the WHO's air quality guideline value); and a full roll-back, assuming a reduction to 2.4 μg/m3. All scenarios used 2017 p.m.2.5 levels as a starting point. Using the concentration response function of the Global Exposure Mortality Model (GEMM), we estimated a total of 7146 (95% CI: 6596-7513) adult (age ≥25 years) deaths attributable to PM2.5 in 2017. The leading causes of death were ischemic heart disease (3437; 95% CI: 3315-3516), stroke (886; 95% CI: 693-1002), lower respiratory infections (531: 95% CI: 414-589), chronic obstructive pulmonary disease (364; 95% CI: 271-420), and lung cancer (274; 95% CI: 236-298). The estimated total annual economic benefit (2017) of reducing PM2.5 concentration levels to 2.4 μg/m3 was USD 0.591 (95% CI: 0.447-0.624) billion per year, using the value of a life year (VOLY) approach, and USD 2.894 (95% CI: 2.671-3.043) billion per year, using the value of a statistical life (VSL) approach.


Death of axotomized retinal ganglion cells delayed after intraoptic nerve transplantation of olfactory ensheathing cells in adult rats.
Intraorbital transection of the optic nerve (ON) always induces ultimate apoptosis of retinal ganglion cells (RGCs) and consequently irreversible defects of vision function. It was demonstrated that transplanted olfactory ensheathing cells (OECs) in partially injured spinal cord have a distant in vivo neuroprotective effect on descending cortical and brain stem neurons. However, this study gave no answers to the question whether OECs can protect the central sensitive neurons with a closer axonal injury because different neurons respond variously to similar axonal injury and the distance between the neuronal soma and axonal injury site has a definite effect on the severity of neuronal response and apoptosis. In the present study, we investigated the effect of transplanted OECs on RGCs after intraorbital ON transection in adult rats. Green fluorescent protein (GFP)-OECs were injected into the ocular stumps of transected ON and a significantly higher number of surviving RGCs was found together with a consistent marked increase in the mRNA and protein levels of BDNF in the ON stump and retina in the OEC-treated group at 7 days, but not 2 and 14 days, time point when compared to the control group. Our findings suggest that OEC transplantation induces the expression of BDNF in the ocular ON stump and retina and delays the death of axotomized RGCs at a certain survival period.


Antigen-specific human T cell factors. I. T cell helper factor: biololgic properties.
The in vitro induction and assay of an ovalbumin-specific human T cell helper factor are described. Peripheral blood T cells, cultured with ovalbumin in a Marbrook-Diener system, produce an antigen-specific factor(ThF120-OA), which can be purified by affinity chromatography. The in vitro studies with ThF120-OA pointed out that in the production of the factor as well as in the factor-B cell interaction the adherent cell determines the genetic restriction. The results of kinetic studies on T helper activities demonstrated that Thf120-OA provides an auxiliary activity at various moments during the differentiation of the human peripheral B cell into an antibody-secreting cell. The observed differences in the mode of action of Th cells and Th factor are discussed.


Influence of genetic variability in toll-like receptors (TLR 2, TLR 4, and TLR 9) on human immunodeficiency virus-1 disease progression.
It has been demonstrated that toll-like receptors (TLR2), TLR4, and TLR9 which were initially known for recognizing bacterial products are involved in the detection of viral components. It was planned to undertake a prospective longitudinal study among ethnically homogeneous antiretroviral treatment and antitubercular treatment naïve human immunodeficiency virus (HIV)-positive patients representing the north Indian population. The aim of the study was to investigate the influence of TLR2, TLR4, and TLR9 polymorphism in HIV disease progression. The present study was designed to investigate genetic polymorphism in TLRs (TLR2, TLR4, and TLR9) among HIV-infected patients with and without TB coinfection. The study population consisted of two groups: (i) HIV-positive patients without TB infection and disease (n = 223, HIV-positive patients); (ii) HIV-positive patients with latent tuberculosis infection (LTBI) (n = 150, HIV-positive LTBI patients). These participants were of either gender between 18 and 60 years of age and treatment naïve for both TB and HIV. HIV-positive and HIV-positive LTBI patients were longitudinally followed up for t2 years to study HIV disease progression. On comparing TLR2 and TLR4 allelic and genotypic frequencies between 306 HIV-positive patients (no TB/AIDS) and 47 HIV-positive patients progressed to active TB/AIDS, no significant difference was observed between the two groups. The frequency of "A" allele in TLR9 was found to be significantly increased in 47 HIV-positive patients who progressed to active TB/AIDS (61.7%) as compared to 42.16% in 306 HIV-positive patients (no TB/AIDS), (P < 0.001). Furthermore, a significantly increased frequency of "AA" genotype in TLR9 was observed in 47 HIV-positive patients progressed to active TB/AIDS (55.32%) as compared to 20.26% in HIV-positive patients (no TB/AIDS). Findings of the present study revealed that genetic variability in TLR9 may influence HIV disease progression. The AA genotype in TLR9 may be associated with progression to TB/AIDS for 2 years in HIV-positive patients.


[Establishment of a digital remote platform for respiratory support and intelligent early warning in intensive care units].
During the disease progression or treatment of critically ill patients with lung injury, the changes in respiratory mechanics are continuous and dynamic. Establishing a digital platform for respiratory support in the ICU, which enables the continuous recording, dynamic analysis, and real-time alerting of numerical and waveform data from mechanical ventilation, can help intensivists improve their understanding of "dynamic respiratory mechanics", improve respiratory therapy and patient outcomes, as well as reduce workload and increase work efficiency. The construction of a dedicated database for mechanical ventilation, based on ventilator waveforms provides essential data support for projects such as respiratory mechanics data algorithm models. This will facilitate the establishment of an auxiliary decision-making system, enable the realization of intelligent mechanical ventilation, and create a new era of dynamic respiratory mechanics.


Genetics and molecular biology of the electron flow for sulfate respiration in desulfovibrio.
Progress in the genetic manipulation of the Desulfovibrio strains has provided an opportunity to explore electron flow pathways during sulfate respiration. Most bacteria in this genus couple the oxidation of organic acids or ethanol with the reduction of sulfate, sulfite, or thiosulfate. Both fermentation of pyruvate in the absence of an alternative terminal electron acceptor, disproportionation of fumarate and growth on H(2) with CO(2) during sulfate reduction are exhibited by some strains. The ability to produce or consume H(2) provides Desulfovibrio strains the capacity to participate as either partner in interspecies H(2) transfer. Interestingly the mechanisms of energy conversion, pathways of electron flow and the parameters determining the pathways used remain to be elucidated. Recent application of molecular genetic tools for the exploration of the metabolism of Desulfovibrio vulgaris Hildenborough has provided several new datasets that might provide insights and constraints to the electron flow pathways. These datasets include (1) gene expression changes measured in microarrays for cells cultured with different electron donors and acceptors, (2) relative mRNA abundances for cells growing exponentially in defined medium with lactate as carbon source and electron donor plus sulfate as terminal electron acceptor, and (3) a random transposon mutant library selected on medium containing lactate plus sulfate supplemented with yeast extract. Studies of directed mutations eliminating apparent key components, the quinone-interacting membrane-bound oxidoreductase (Qmo) complex, the Type 1 tetraheme cytochrome c(3) (Tp1-c(3)), or the Type 1 cytochrome c(3):menaquinone oxidoreductase (Qrc) complex, suggest a greater flexibility in electron flow than previously considered. The new datasets revealed the absence of random transposons in the genes encoding an enzyme with homology to Coo membrane-bound hydrogenase. From this result, we infer that Coo hydrogenase plays an important role in D. vulgaris growth on lactate plus sulfate. These observations along with those reported previously have been combined in a model showing dual pathways of electrons from the oxidation of both lactate and pyruvate during sulfate respiration. Continuing genetic and biochemical analyses of key genes in Desulfovibrio strains will allow further clarification of a general model for sulfate respiration.


Convalescent plasma to treat coronavirus disease 2019 (COVID-19): considerations for clinical trial design.
Case series studying convalescent plasma use in the treatment of COVID-19 have been promising, but additional, high-quality studies are needed to determine the efficacy of the treatment when applied for prophylaxis, for early phases of illness, and for severe illness. Previous studies of convalescent plasma in treating other viral diseases have identified factors to consider when designing treatment protocols, including timing of administration relative to onset of illness, timing of donation relative to resolution of symptoms, severity of illness of the donor, pretransfusion serology of the recipient, and antibody titers of the donor. There are many clinical trials studying treatment of, and prophylaxis against, COVID-19 using convalescent plasma. In addition to clinical trials, the FDA also allows treatment through two other pathways: the "Expanded Access to Convalescent Plasma for the Treatment of Patients with COVID-19" protocol, and emergency investigational new drug applications. The FDA also provides criteria for donation of convalescent plasma.


Posters as an educational strategy.
Posters are visual aids that are well suited to use as independent sources of information or as support for other presentation formats. By design, the message displayed is brief, constant, and interactive with the viewer. Guidelines for developing a poster include careful delineation of content, knowledge of audience needs, and the environment or setting for the poster. The application of basic design elements, such as simplicity of composition, attractive color combinations, and title spacings, results in a presentation mode that is both attracting and lingering.


High-accuracy measurement system for the refractive index of air based on a simple double-beam interferometry.
A measurement system based on a simple double-beam interferometry is built to realize the measurement of air refractive index with high accuracy. The basic principle of the system is that, through measuring the change of optical path difference caused by rapid and smooth vacuumization, measurement of refractive index of air is converted to length measurement. Error correction and signal processing are studied to ensure high-accuracy measurement of the refractive index of air. Three applicable methods are used in system. The system based on the methods realize the subdivision and counting of interference fringe by software with three-error correction, error compensation for the end-window plates' thickness change caused by vacuumization, steady realization of high vacuum conditions. To verify the accuracy and reliability of the system, the measurement results are compared with that obtained from the method based on empirical Edlén's formula. Analysis result shows that the expanded measurement uncertainty of the system is U = 5×10-9, with k = 2. The system can be used to compensate the laser wavelength error caused by the refractive index of air with high accuracy.


Analysis of the process of translation of knowledge regarding early childhood at the undergraduate level.
Objective To analyze innovative contents on Early Child Development Promotion. Method This action-research involves nine faculties from four Higher Education Institutions at inner-state of São Paulo, Brazil.Data were collected by syllabi analyses (2009-2011), interviews and focus group. We have adopted an ECDP underpinning from international consensus, thus evaluating KT Results We have found relevant incorporation between teaching and extension in Nursing (87,5%) and Psychology (75%) undergraduate courses, while Pedagogy was restricted to teaching. Conclusion This KT evaluation has evinced innovative potential of extension, regardless teaching and research, for a better Early Childhood.


Intrathymic differentiation of cytotoxic T lymphocyte (CTL) precursors. I. The CTL immunocompetence of peanut agglutinin-positive (cortical) and negative (medullary) Lyt 123 thymocytes.
To analyze the developmental and functional interrelationship between cortical and medullary thymocytes, the peanut agglutinin-(PNA) binding capacity was used to separate thymocytes into PNA+ (cortical) and PNA- (medullary) thymocytes. Virtually, all positively selected PNA+ thymocytes (90% of the overall thymocyte population) expressed the Lyt 123 phenotype, whereas 90% of negatively selected PNA- thymocytes expressed Lyt 1 alloantigens, about 10% being Lyt 123 thymocytes. Provided, the requirement of Lyt 1 T helper cells was bypassed by Interleukin 2, a nonspecific mediator of T help, PNA+ Lyt 123 thymocytes mounted cytotoxic T cell responses comparable in magnitude to that of peripheral T cells. Their repertoire included antigenic disparities coded for by the complete MHC complex, H-2K, I-A, H-2D, mutational events at H-2K, as well as antigenic disparities expressed on TNP conjugated- and Sendai virus-infected syngeneic cells. PNA- Lyt 123 thymocytes represent a highly reactive pool of primary cytotoxic T lymphocyte (CTL) precursors for both alloreactive and H-2-restricted CTL responses. Since PNA- thymocytes include also Lyt 1 T helper cells, PNA- responder thymocytes are able to mount autonomously (CTL responses. Our data are first to provide direct evidence that Lyt 123 cells represent a common source of alloreactive and H-2-restricted CTL precursors in unprimed lymphocyte populations. Moreover, the apparent immunocompetence of cortical PNA+ thymocytes is now explained by their lack of T helper cells.


Associations between paratuberculosis ELISA results and test-day records of cows enrolled in the Irish Johne's Disease Control Program.
The effect of the Mycobacterium avium ssp. paratuberculosis (MAP) ELISA status on test-day milk performance of cows from Irish herds enrolled in the pilot national voluntary Johne's disease control program during 2013 to 2015 was estimated. A data set comprising 92,854 cows and 592,623 complete test-day records distributed across 1,700 herds was used in this study. The resulting ELISA outcome (negative, inconclusive, and positive) of each cow within each year of the program was used to allocate the cow into different scenarios representing the MAP status. At MAPscenario1, all cows testing ELISA nonnegative (i.e., inconclusive and positive) were assigned a MAP-positive status; at MAPscenario2 only cows testing ELISA-positive were assigned a MAP-positive status; at MAPscenario3 only cows testing ELISA nonnegative (inconclusive or positive) and gathered exclusively from herds where at least 2 further ELISA nonnegative (inconclusive or positive) cows were found were assigned a MAP-positive status; at MAPscenario4 only cows testing ELISA-positive that were gathered exclusively from herds where at least 2 further ELISA-positive cows were found were assigned a MAP-positive status. Milk outputs based on test-day records were standardized for fat and protein contents (SMY) and the effect of MAP ELISA status on the SMY was estimated by a linear mixed effects model structure. The SMY mean difference recorded at test day between cows with a MAP-positive status and those with a MAP-negative status within MAPscenario1 was estimated at -0.182 kg/test day; the mean difference was -0.297 kg/test day for MAPscenario2; for MAPscenario3 mean difference between MAP-positive status and MAP test-negative cows was -0.209 kg/test day, and for MAPscenario4, the difference was -0.326 kg/test day.


Characterisation of a Spontaneous Mutant of Lemna gibba G3 (Lemnaceae).
A spontaneous mutant of the duckweed Lemna gibba clone no. 7796 (known as strain G3, WT) was discovered. In this mutant clone, L. gibba clone no. 9602 (mt), the morphological parameters (frond length, frond width, root length, root diameter) indicated an enlarged size. A change in the frond shape was indicated by the decreased frond length/width ratio, which could have taxonomic consequences. Several different cell types in both the frond and the root were also enlarged. Flow cytometric measurements disclosed the genome size of the WT as 557 Mbp/1C and that of the mt strain as 1153 Mbp/1C. This represents the results of polyploidisation of a diploid clone to a tetraploid one. The mutant clone flowered under the influence of long day-treatment in half-strength Hutner's medium in striking contrast to the diploid WT. Low concentration of salicylic acid (<1 µM) induced flowering in the tetraploid mutant but not in the diploid plants. The transcript levels of nuclear-encoded genes of the photosynthetic apparatus (CAB, RBCS) showed higher abundance in light and less dramatic decline in darkness in the mt than in WT, while this was not the case with plastid-encoded genes (RBCL, PSAA, PSBA, PSBC).


Sympathetic ophthalmia after 23-gauge transconjunctival sutureless vitrectomy.
We report a case of a sympathetic ophthalmia that occurred after 23-gauge transconjunctival sutureless vitrectomy for a retinal detachment. A 41-year-old Japanese woman underwent combined phacoemulsification with intraocular lens implantation and 23-gauge transconjunctival sutureless vitrectomy for a rhegmatogenous retinal detachment in the right eye. Endolaser photocoagulation and silicone oil tamponade were used to manage inferior retinal holes. Four weeks after the surgery, she returned with a 5-day history of reduced vision and metamorphopsia in her left eye. Slit-lamp examination showed a shallow anterior chamber in the right eye and moderate anterior uveitis bilaterally. Silicone oil bubbles and pigment dispersion were observed in the subconjunctival space adjacent to the right eye's superonasal sclerotomy site. Fundus examination showed multifocal serous retinal detachments in both eyes. A diagnosis of sympathetic ophthalmia was made and the patient was treated with intensive topical and systemic steroids. The subretinal fluid cleared in both eyes following treatment. Twelve months after the onset of inflammation, the patient's condition was stable on a combination of oral cyclosporine and topical steroids. Sunset glow retinal changes remain, but there has been no evidence of recurrent inflammation. Sympathetic ophthalmia can develop after 23-gauge transconjunctival sutureless vitrectomy despite its smaller sclerotomy size. We recommend that special care should be taken to inspect for adequate closure of sclerotomy sites at the end of this operation.


Pentadactylin: an antimicrobial peptide from the skin secretions of the South American bullfrog Leptodactylus pentadactylus.
Norepinephrine-stimulated skin secretions were obtained from male specimens of the South American bullfrog, Leptodactylus pentadactylus and shown to contain two peptides that inhibited the growth of microorganisms. The primary structure of a previously undescribed peptide, termed pentadactylin, was established as Gly-Leu-Leu-Asp-Thr-Leu-Lys-Gly-Ala-Ala-Lys-Asn-Val-Val-Gly-Ser-Leu-Ala-Ser-Lys-Val-Met-Glu-Lys-Leu.NH2. The second peptide, which differs from pentadactylin by eight amino acid residues, is identical to fallaxin previously isolated from skin secretions of the Caribbean mountain chicken frog L. fallax. Pentadactylin inhibited the growth of reference strains of both Gram-negative bacteria (Escherichia coli, Enterobacter cloacae, Klebsiella pneumoniae, Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus group B) but potencies were relatively low (MIC values in the range 25-200 microM). The peptide showed very low hemolytic activity against human erythrocytes (LD50>400 microM).


Future Perspectives in the Diagnosis and Treatment of Liver Disease Associated with Alpha-1 Antitrypsin Deficiency.
Alpha-1 antitrypsin deficiency (AATD) is one of the most common genetic diseases and is caused by mutations in the SERPINA1 gene. The homozygous Pi*Z variant is responsible for the majority of the classic severe form of alpha-1 antitrypsin deficiency, which is characterized by markedly decreased levels of serum alpha-1 antitrypsin (AAT) with a strong predisposition to lung and liver disease. The diagnosis and early treatment of AATD-associated liver disease are challenges in clinical practice. In this review, the authors aim to summarize the current evidence of the non-invasive methods in the assessment of liver fibrosis, as well as to elucidate the main therapeutic strategies under investigation that may emerge in the near future.


The WTS report on the current status of women in cardiothoracic surgery.
The purpose of this work was to assess career demographics, professional activities, and career satisfaction of board-certified female cardiothoracic surgeons in the United States, 50 years after certification of the first women diplomats by the American Board of Thoracic Surgery (ABTS). All ABTS-certified women were surveyed anonymously in December 2010, using surveymonkey.com. Questions were in five categories: demographics, training, practice activities, activities of nonpracticing cardiothoracic surgeons, and career satisfaction. Respondents were grouped by year of certification: group 1 (1961 to 1999) and group 2 (2000 to 2010). Broad comparisons to the entire thoracic surgery workforce were based on The Society of Thoracic Surgeons and American Association for Thoracic Surgery 2009 practice survey. Of the 204 living female diplomats, 190 were surveyed, as 14 (7%) were unavailable owing to lack of contact information. Survey response rate was 64% (121 of 190). Mean respondent's age was 48 years (range, 35 to 74), with the majority being Caucasian (94 of 121). Women spent a mean of 9.1 years in training, and 56% (68 of 121) reported non-Accreditation Council for Graduate Medical Education training time. Duration of training and resultant debt has increased over time, as respondents in group 1 (n=52) reported training for 8.5 years versus 9.5 years in group 2 (n=68; p=0.01), and a doubling of graduates with educational debt more than $100,000 from 19% to 41%, respectively (p=0.003). The average number of years in practice was 8 (range, 1 to 30), with the majority working in urban setting (65 of 106), in group practices of 2 to 10 surgeons (82 of 106), and as the sole female surgeon in their group (84 of 106). Of the 54 women with academic appointments, more than 60% (33 of 54) are at the instructor or assistant professor level, but 18% (10 of 54) are full professors. Nearly a third (16 of 54) have secured research funding, and 20% (11 of 54) have protected research time. Job satisfaction is high, with 64% (76 of 118) reporting being always or almost always satisfied with their career, and fewer than 9% (11 of 118) would choose a different career. Although demand on time is the greatest source of dissatisfaction, workplace politics for group 1 and lack of support for group 2 are significant issues. Only 12 respondents are no longer practicing, with the majority leaving because of retirement, health issues, or career advancement. Women represent a minority of cardiothoracic surgeons in the United States. The numbers in academic versus private practice are roughly equal, with high levels of job satisfaction in both. Importantly, 90% of surveyed women remain in practice and are academically productive; 50% entered the profession in the past 10 years. The exponential increase in the number of women in the field over the past 10 years provides optimism for continued recruitment.


Treatment of child abuse.
Standards of care have recently been established for the diagnosis and treatment of child abuse. This article addresses the key areas of treatment with which each primary care physician should be acquainted. As part of a community-based approach to this problem, the physician can positively impact the prognosis for the victimized child and his or her family.


Death caused by possible unrecognized (too Late Recognized) Mycobacterium gordonae infection in a patient with angioimmunoblastic T-cell lymphoma.
Here, we present possible death caused by Mycobacterium gordonae infection in a patient with angioimmunoblastic T-cell lymphoma. Our patient was severely immunocompromised in whom we suspect to an infection, but we did not have isolates until she died. After she died, we received a positive sputum culture of M. gordonae. We conclude that when having severely immunocompromised patients with suspicion of infection but without isolates we should always consider the saprophytic mycobacteria. These mycobacteria require a long period of isolation, but patients with these mycobacteria are potentially curable if appropriate treatment is applied for a sufficiently long period.


[Total heterotopic transplant of the small intestine in rats. Technical considerations on organ acquiring, preservation and transplantation].
In this paper, we report the modifications incorporated in the technique of the total heterotopic small bowel transplantation in the rat. Since the original description of Monchik and Russell in 1971, we evaluate all technical, preservation and transplantation aspects of the procedure. We review all the results from our laboratories and introduced new concepts on management and treatment. A total of 80 Sprague-Dawley rats were divided in 3 groups (immediate fresh transplant, 24 hours preservation with UW solution and with ADAAV) with immediate results of 80, 50 and 70 per cent survival respectively for the groups studied. The advantages of our technique are reviewed to bring about the best steps that need to be added for clinical transplantation.


Wastes as Aggregates, Binders or Additions in Mortars: Selecting Their Role Based on Characterization.
The production of waste has increased over the years and, lacking a recycle or recovery solution, it is forwarded to landfill. The incorporation of wastes in cement-based materials is a solution to reduce waste deposition. In this regard, some researchers have been studying the incorporation of wastes with different functions: aggregate, binder and addition. The incorporation of wastes should take advantage of their characteristics. It requires a judicious analysis of their particles. This research involves the analysis of seven industrial wastes: biomass ashes, glass fibre, reinforced polymer dust, sanitary ware, fluid catalytic cracking, acrylic fibre, textile fibre and glass fibre. The main characteristics and advantages of each waste are enunciated and the best type of introduction in mortars is discussed. The characterization of the wastes as particles is necessary to identify the most suitable incorporation in mortars. In this research, some wastes are studied with a view to their re-use or recycling in mortars. Thus, this research focuses on the chemical, physical and mechanical characterization of industrial wastes and identification of the potentially most advantageous type of incorporation.


Variable predation regimes predict the evolution of sexual dimorphism in a population of threespine stickleback.
Sexual dimorphism is widespread in nature and can be influenced by sex-specific natural selection resulting from ecological differences between the sexes. Here we show that contrasting life-history pressures and temporal shifts in ecology can exert a strong influence on the evolution of sexual dimorphism. The bony spines exhibited by stickleback are a defense against open-water avian predators but may be detrimental against benthic macroinvertebrate predators. Female stickleback from a coastal lake in western Canada occupy a more open-water ecological niche and exhibit greater dorsal and pelvic spine number than males, but the magnitude of these differences varies among life-history stages, seasons, and years. Ecological data on diet and parasite load and 62 seasonal estimates of selection over a 15-year period show that selection favors increased spine number in females and decreased spine number in males, but only when pronounced ecological differences between the sexes results in differential exposure to the two, divergent predation regimes. Thus occasional sex-reversals in ecological niche reversed the mode of selection. These processes caused a predictable response in the subsequent generation, indicating that divergent predation caused evolutionary change in dimorphism. However, temporal oscillations in sex-specific selection resulted in no net change in sexual dimorphism over the 15-year study period, indicating that fluctuations in directional selection can be responsible for long-term stasis. Replicated shifts in selective regime can demonstrate the primacy of ecological processes in driving evolution and our results illustrate how such shifts are detectable using long-term monitoring of natural populations.


The 1,25D3 -MARRS receptor/PDIA3/ERp57 and lifespan.
Using MRI on mice bearing a targeted knockout (KO) of the 1,25D3 -MARRS receptor/PDIA3/ERp57 we found that they had decreased body fat relative to their littermate (LM) controls, a condition associated with increased lifespan. Others have found that lower body fat is correlated with decreased lipid droplets in intestinal cells that may be mediated by a factor secreted by germ cells (possibly estradiol). In a reducing environment estradiol competed for binding to the 1,25D3-MARRS receptor/PDIA3/ERp57. A consequence of this was that estradiol stimulated calcium uptake in enterocytes isolated from LM mice. In time course studies, lipid droplets increased in response to 1 nM estradiol from 1-5 D of culture, relative to corresponding controls, while at 6 and 7 D this steroid decreased lipid droplets. Enterocytes from LM or KOs incubated with estradiol for 1-4 D showed the hormone increased lipid droplets. Using the 4 D culture period, 1 and 10 nM estradiol significantly increased the number of lipid droplets in cells from LM mice by 40-60%, compared to equivalent conditions in KO mice. In assessing signal transduction pathways, the hormone increased phospho-Akt levels, but no differences were observed in phospho-mTORC1, or phospho-S6K (although cells from chicks did exhibit a hormone-mediated difference). Finally, the remaining mice (which had stopped reproducing) were allowed to die naturally and lifespan recorded. LM mice lived 687 ± 77 D (without an outlying value) while KO mice lived 740 D ± 80 D. These data suggest the 25D3 -MARRS receptor/PDIA3/ERp57 may contribute to the length of lifespan in mammals.


Use of a Mobile Application for Self-Monitoring Dietary Intake: Feasibility Test and an Intervention Study.
Given the increasing social and economic burden of chronic disease and the need for efficient approaches to prevent and treat chronic disease, emphasis on the use of information and communication technology (ICT)-based health care has emerged. We aimed to test the feasibility of a mobile application, Diet-A, and examine whether Diet-A could be used to monitor dietary intake among adolescents. In a three-month pre-post intervention study, 9 male and 24 female high school students aged 16-18 years consented and participated in this study. Participants were instructed to record all foods and beverages consumed using voice or text mode input. Nutrient intake was measured using 24-h recalls pre- and post-intervention. We compared nutrient intake data assessed by Diet-A application with those assessed by 24-h recalls. Participants tended to underreport intakes of nutrients compared to those assessed by two 24-h recalls. There were significant decreases in sodium (p = 0.04) and calcium (p = 0.03) intake between pre- and post-intervention. Of participants who completed questionnaires of feasibility (n = 24), 61.9% reported that they were satisfied using the application to monitor their food intake, and 47.7% liked getting personal information about their dietary intake from the application. However, more than 70% of participants answered that it was burdensome to use the application or that they had trouble remembering to record their food intake. The mobile application Diet-A offers the opportunity to monitor dietary intake through real-time feedback. However, use of Diet-A may not provide accurate information on the food intake of adolescents, partly because of the recording burden.


Development of the β-lactam type molecular scaffold for selective estrogen receptor α modulator action: synthesis and cytotoxic effects in MCF-7 breast cancer cells.
The estrogen receptors (ERα and ERβ) which are ligand inducible nuclear receptors are recognized as pharmaceutical targets for diseases such as osteoporosis and breast cancer. There is an increasing interest in the discovery of subtype Selective Estrogen Receptor Modulators (SERMs). A series of novel β-lactam compounds with estrogen receptor modulator properties have been synthesized. The antiproliferative effects of these compounds on human MCF-7 breast tumor cells are reported, together with binding affinity for the ERα and ERβ receptors. The most potent compound 15g demonstrated antiproliferative effects on MCF-7 breast tumor cells (IC50 = 186 nM) and ERα binding (IC50 = 4.3 nM) with 75-fold ERα/β receptor binding selectivity. The effect of positioning of the characteristic amine containing substituted aryl ring (on C-4 or N-1 of the β-lactam scaffold) on the antiproliferative activity and ER-binding properties of the β-lactam compounds is rationalized in a molecular modeling study.


Understanding the Influence of [EMIM]Cl on the Suppression of the Hydrogen Evolution Reaction on Transition Metal Electrodes.
We have studied the influence of low concentrations (0.1 M) of the ionic liquid 1-ethyl-3-methylimidazolium chloride ([EMIM]Cl) on suppressing the hydrogen evolution reaction (HER) using polycrystalline Ag, Cu, and Fe electrodes in aqueous acidic and basic media. HER suppression is generally desired when aiming to catalyze other reactions of interests, e.g., CO2 electro-reduction. Cyclic voltammetry and chronoamperometry measurements were performed at potentials between -0.2 and -0.8 V versus the reversible hydrogen electrode (RHE) to investigate HER activity in a simulated CO2 electrolysis environment without the CO2. In an acidic electrolyte, a decrease in HER activity was observed for all three electrodes with the largest effect being that of Fe, where the HER activity was suppressed by 75% at -0.5 V versus RHE. In contrast to the effect of [EMIM]Cl in an acidic electrolyte, no HER suppression was observed in basic media. Using 1H nuclear magnetic resonance spectroscopy on the electrolyte before and after electrolysis, it was determined that [EMIM]Cl breaks down at both the working and counter electrodes under reaction conditions under both acidic and basic conditions. These results underscore the challenges in employing ionic liquids for electrochemical reactions such as CO2 reduction.


Caregivers of people at the end of life: emerging evidence.
This review aims to identify and highlight recent evidence from studies that aim to improve outcomes for caregivers of patients living with life-limiting progressive conditions. It appears that although the volume and quality of studies reporting outcomes for this population is increasing, there is still a paucity of evidence that has reliable quality and can inform policy and practice. One trial has been reported, which found that a one-to-one psychoeducational intervention found no change in distress at 1 week after intervention but found improvements in preparedness and competence. Follow-up data at 8 weeks found that distress worsened significantly less for those with one home visit but surprisingly not for those who received two visits (in this three-arm trial) compared with controls. Although the evidence of outcome studies is small, the research agenda is broadening to include nontraditional families and caregivers in low-and middle-income countries.The recent trial of psychoeducational interventions suggests that longer-term benefits are present.


The relationship between role conception and ethical behaviour of student nurses in Hong Kong.
This paper was designed to explore the relationships of three role conception types (the professional, bureaucratic and service role conceptions) to the ethical behaviour of student nurses from the apprenticeship and degree nursing programmes in Hong Kong. The effect of role discrepancy on ethical behaviour will also be explored. A nonprobability convenience sampling of 140 certificate students from a hospital-based training course and 81 degrees nursing students from a tertiary programme were selected. Role conception and role discrepancy were measured by the modified Nursing Role Conception scale originally developed by Corwin. For ethical behaviour, the Judgement About Nursing Decisions scale developed by Ketefian was used. Multiple regression analyses showed that the ideal professional role conception was a significant predictor, accounting for 17% of the variance in the ideal ethical score of the degree students. Actual service role conception was a better predictor of the actual ethical score, explaining 10% and 14% of its variance for the certificate and degree students respectively. Professional and bureaucratic role discrepancies together were found to have a negative effect on the actual ethical behaviour of the degree students. These results suggest that professional values that have been developed through socialization in nurse education programmes could benefit patients only when degree students, in particular, could adapt successfully to the demands of bureaucratic organization.


Adrenal medullary grafts restore olfactory deficits and catecholamine levels of 6-OHDA amygdala lesioned animals.
Aside from motor and cognitive deficits, Parkinson patients also manifest a little-studied olfactory deficit. Since in Parkinson's disease there is a dopamine depletion of the amygdala due to mesocorticolimbic system degeneration, we decided to test olfactory and taste performance of 6-OHDA amygdala lesioned rats, as well as the possible restoration of either function with adrenal medullary transplants. Two 6-OHDA lesioned groups and one control group were tested in the potentiation of odor by taste aversion paradigm. On taste aversion none of the groups showed any impairment. In contrast, the 6-OHDA lesioned rats showed a marked impairment in olfactory aversion. At this point, one of the lesioned groups received a bilateral adrenal medullary graft within the lesioned area. After two months, all groups were submitted again to the behavioral paradigm. Taste remained unaffected, but the lesioned only group did not recover either olfactory aversion or normal catecholamine levels. The grafted group, on the other hand, restored olfactory aversion and catecholamine levels. It can be concluded from this study that catecholamine depletion of the amygdala is sufficient to produce a selective olfactory deficit, not accompanied by taste impairments, and that such a deficit can be reversed by adrenal medullary transplants, which in turn restore catecholamine levels.


Rectal Trauma: Evidence-Based Practices.
The management of rectal trauma has often been lumped in with colon trauma when, in fact, it is a unique entity. The anatomic nature of the rectum (with its intra- and extraperitoneal segments) lends itself to unique circumstances when it comes to management and treatment. From the four Ds (debridement, drainage, diversion, and distal irrigation), the management of rectal trauma has made some strides in light of the experiences coming out of the recent conflicts overseas as well as some rethinking of dogma. This article will serve to review the anatomy and types of injuries associated with rectal trauma. A treatment algorithm will also be presented based on our current literature review. We will also address controversial points and attempt to give our opinion in an effort to provide an update on an age-old problem.


Comparative transcriptomics of porcine liver-resident CD8αdim, liver CD8αhigh and circulating blood CD8αhigh NK cells reveals an intermediate phenotype of liver CD8αhigh NK cells.
Liver-resident NK (lrNK) cells have been studied in humans as well as in mice. Unfortunately, important differences have been observed between murine and human lrNK cells, complicating the extrapolation of data obtained in mice to man. We previously described two NK cell subsets in the porcine liver: A CD8αhigh subset, with a phenotype much like conventional CD8αhigh NK cells found in the peripheral blood, and a specific liver-resident CD8αdim subset which phenotypically strongly resembles human lrNK cells. These data suggest that the pig might be an attractive model for studying lrNK cell biology. In the current study, we used RNA-seq to compare the transcriptome of three porcine NK cell populations: Conventional CD8αhigh NK cells from peripheral blood (cNK cells), CD8αhigh NK cells isolated from the liver, and the liver-specific CD8αdim NK cells. We found that highly expressed transcripts in the CD8αdim lrNK cell population mainly include genes associated with the (adaptive) immune response, whereas transcripts associated with cell migration and extravasation are much less expressed in this subset compared to cNK cells. Overall, our data indicate that CD8αdim lrNK cells show an immature and anti-inflammatory phenotype. Interestingly, we also observed that the CD8αhigh NK cell population that is present in the liver appears to represent a population with an intermediate phenotype. Indeed, while the transcriptome of these cells largely overlaps with that of cNK cells, they also express transcripts associated with liver residency, in particular CXCR6. The current, in-depth characterization of the transcriptome of porcine liver NK cell populations provides a basis to use the pig model for research into liver-resident NK cells.