Preparation of graphene by exfoliating graphite in aqueous fulvic acid solution and its application in corrosion protection of aluminum.
Liquid phase exfoliation (LPE) method has great potential for the large-scale production of graphene due to its simplicity, scalability, and low cost. In this work, fulvic acid (FA) was chosen to assist the exfoliation of graphite into graphene for the first time via sonication in aqueous medium. The concentration of obtained graphene dispersion can reach 0.63 ± 0.04 mg mL-1. The graphene flakes mostly consisted of 1-5 layers with sizes range in submicron to micron and few defects in the basal-plane. The π-π interaction between graphene and FA, along with the electrostatic repulsion between negatively charged FA, played a major role in stabilization of the graphene dispersion. By adjusting the pH of graphene dispersion to 14, the nanosheets of graphene came to flocculation. The formed graphene slurry is favorable for storage and transportation due to the greatly decreased volume. The annealed coating of FA-graphene on aluminum sheets was used as corrosion inhibitor for aluminum in 0.5 M H2SO4 and 0.6 M NaCl solutions, with inhibition efficiencies of up to 85.5% and 99.4%, respectively. This shows that as-prepared graphene has great potential applications in the anti-corrosion of aluminum.


Selective hepatobiliary transport of nordeoxycholate side chain conjugates in mutant rats with a canalicular transport defect.
Canalicular transport of bilirubin diglucuronide, dibromosulfophthalein and several glutathione conjugates is deficient in mutant TR- rats. In contrast, transport of cholyltaurine (taurocholate), a conjugated bile acid, is normal. Previous studies using normal rats have shown that C23 nor-dihydroxy bile acids are conjugated with sulfate or glucuronide during hepatic transport in contrast to the natural C24 bile acids, which are amidated with glycine or taurine. Studies were performed to test the hypothesis that (a) in the TR- rat, nordeoxycholate would be conjugated with glucuronate or sulfate just as in the normal rat, and (b) that such conjugates would have defective biliary secretion. [C23-14C]Nordeoxycholate was administered intravenously to bile fistula rats (TR- and normal), and the biliary recovery of metabolites was assessed by chromatography and mass spectrometry. In both groups of rats, the major biotransformation product of nordeoxycholate was the side chain (23-ester) glucuronide. Conjugation on the nucleus with sulfate and glucuronide at the 3-position (ethereal linkage) also occurred, as well as amidation at the C23 carboxylic acid group. In the mutant rats, biliary secretion of the 3-sulfate and 3-glucuronide conjugates was less than 10% and 1%, respectively, of that of normal rats, whereas biliary secretion of the 23-ester glucuronide and the 23-taurine amidate, as well as unchanged nordeoxycholate, was not decreased. Canalicular secretion of nor-bile acid 3-ether glucuronides and 3-sulfates appears to involve the "bilirubin transport system," which is deficient in mutant rats. Canalicular secretion of unconjugated, amidated or esterified nordeoxycholate is mediated via another pathway, probably the "bile acid transport system."(ABSTRACT TRUNCATED AT 250 WORDS)


AAGL practice report: practice guidelines for laparoscopic subtotal/supracervical hysterectomy (LSH).
The first subtotal abdominal hysterectomy was described by Charles Clay in 1843, and the first laparoscopic subtotal hysterectomy (LSH) was described by Semm [1] in 1991. Whether to retain or remove the cervix remains controversial, with surgeons citing sexual satisfaction and prevention of pelvic organ prolapse as indicators for retention [2]. Because the only absolute indication for cervical removal is malignancy or its precursors, debate has continued as to the optimum surgical approach to hysterectomy for other indications. The evidence obtained from evaluating the effects of retaining the cervix, via any surgical approach, on sexual, urinary, and bowel function remains controversial [3-11]. The literature evaluating LSH is limited, and only 3 randomized controlled trials (RCTs), including 342 women, have reported psychologic outcomes, complications, and additional cervical procedures [4,12,13]. For the abdominal equivalent, there are 9 RCTs, including 1553 women, and a Cochrane review reported few important differences between the 2 approaches [8]. No such comparative data are available for LSH. This practice guideline will evaluate the evidence for LSH. This report was developed under the direction of the Practice Committee of the AAGL as a service to their members and other practicing clinicians.


Comparison of endogenous amino acid losses in broilers when offered nitrogen-free diets with differing ratios of dextrose to corn starch.
The nitrogen-free diet (NFD) method is widely used to determine the ileal endogenous amino acids (IEAAs) losses in broiler chickens. Starch and dextrose are the main components of NFD, but the effects of their proportion in the NFD on the IEAAs and the digestive physiology of broilers are still unclear. This preliminary study aims to explore the best proportion of glucose and corn starch in NFD to simulate the normal intestinal physiology of broilers, which helps to improve the accuracy of IEAAs determination. For this purpose, 28-day-old broiler chickens were allocated to five treatment groups for a 3-day trial, including a control group and four NFD groups. The ratios of dextrose to corn starch (D/CS) in the four NFD were 1.00, 0.60, 0.33, and 0.14, respectively. Results noted that NFD significantly reduced serum IGF-1, albumin, and uric acid levels compared with the control (P < 0.05), except there was no difference between group D/CS 0.33 and the control for IGF-1. The increased Asp, Thr, Ser, Glu, Gly, Ala, Val, Ile, Leu, His, Tyr, Arg, and Pro contents of IEAAs were detected in broilers fed the NFD with a higher ratio of D/CS (1.00 and 0.60) compared to the lower ratio of D/CS (0.33 and 0.14). Moreover, ileal digestibility of dry matter and activity of digestive enzymes increased as the D/CS elevated (P < 0.001). Further investigation revealed that the number of ileal goblet cells and Mucin-2 expression were higher in the group with D/CS at 1.00 when compared with group D/CS 0.33 and the control (P < 0.05). Microbiota analysis showed that NFD reshaped the gut microbiota, characterized by decreased microbial diversity and lower abundance of Bacteroidetes, and increased Proteobacteria (P < 0.05). Our results indicate that a higher D/CS ratio (1.00 and 0.60) in NFD increases IEAAs by promoting digestive enzymes and mucin secretion. However, the excessive proportion of starch (D/CS = 0.14) in NFD was unsuitable for the chicken to digest. The chickens fed with NFD with the D/CS ratio at 0.33 were closer to the normal digestive physiological state. Thus, the ratio of D/CS in NFD at 0.33 is more appropriate to detect IEAAs of broiler chickens.


Recognising and responding to outbreaks of hepatitis A associated with child day-care centres.
To assess the appropriateness of a protocol for recognising and responding to outbreaks of hepatitis A in child day-care centres and to determine if measles-mumps-rubella (MMR) vaccine was given too soon following the administration of normal human immunoglobulin (NIGH) to young children to control the outbreaks. Prospective surveillance to recognise cases of hepatitis A associated with, and outbreaks of hepatitis A in, day-care centres. The percentage of initial ('sentinel') cases of hepatitis A associated with day-care centres that were subsequently recognised as also being 'index' cases of outbreaks of hepatitis A in the centres, and the number of children 9-13 months of age when given NIGH who were subsequently given MMR less than three months later. Only 18 (16%) of the 114 sentinel day-care associated cases of hepatitis A were also index cases of outbreaks of hepatitis A in their respective centres. A total of 105 cases of hepatitis A were associated with the 18 outbreak centres; NIGH was administered to 928 (78%) of the attendee children, and to 105 (82%) of the susceptible staff, at the 18 centres. Three of the five children 9-13 months of age when given NIGH were given MMR less that three months later. Although outbreaks of hepatitis A were common events in day-care centres in north Queensland during the two-year study period, a single case of hepatitis A associated with a centre was a poor predictor of an outbreak within that centre. Precautions must be taken to ensure that live vaccines are not administered to young children too soon after NIGH.


Treatment of drug-susceptible tuberculosis among people living with human immunodeficiency virus infection: an update.
The present review describes recent advances in the treatment of drug-susceptible tuberculosis (DS-TB) among people living with human immunodeficiency virus (PLWH). Higher than standard rifampicin doses (>10 mg/kg/day) are well tolerated and have improved sterilizing activity. Standard pyrazinamide doses may result in low drug exposures; modeling reveals that higher doses (>25 mg/kg/day) may be required to reach target levels, although safety is unknown. Four-month fluoroquinolone-containing regimens are not recommended in the 2017 World Health Organization DS-TB treatment guidelines. These guidelines also recommend fixed-dose combination (FDC) therapy over single drug formulations based on patient preference, though FDC is not associated with improved outcomes. Treatment for 6 months is recommended, with an emphasis on expanded antiretroviral therapy (ART) coverage and monitoring for relapse among those not started on ART within 8 weeks of tuberculosis treatment. Directly observed therapy (DOT) is recommended over self-administered therapy, as is daily therapy over intermittent therapy - both are associated with better tuberculosis outcomes. Current WHO tuberculosis treatment guidelines recommend 6 months of daily tuberculosis treatment for PLWH who have DS-TB, and timely ART initiation. Higher rifampin and pyrazinamide doses may enhance treatment effectiveness, but safety data are needed. DOT and FDC therapy are recommended.


Clinical efficacy and safety of mirabegron and imidafenacin in women with overactive bladder: A randomized crossover study (the MICRO study).
We aimed to compare the efficacy and safety of mirabegron, a β3-adrenoceptor agonist, and imidafenacin, an anticholinergic agent, in overactive bladder patients. We conducted a multicenter, prospective randomized cross-over study at 5 hospitals in Japan from December 2012 to June 2015. We enrolled female patients with overactive bladder aged ≥50 years, who had never received treatment for the condition. The patients were assigned to Group A or B. Group A patients were administered mirabegron (50 mg per day) for 8 weeks, followed by a 2-week washout period, and then imidafenacin (0.2 mg per day) for 8 weeks. This order of drug administration was reversed in Group B. A total of 33 and 18 patients in Group A and 37 and 26 patients in Group B continued to receive treatment at weeks 8 and 18, respectively. Mirabegron administration significantly improved overactive bladder symptom score (OABSS), the urinary frequency per 24 hr, voided volume per micturition, and number of nocturia episodes per night at week 8. Moreover, imidafenacin administration improved all these variables, except for the number of nocturia episodes per night at week 8. No significant difference was observed in the drug effects between mirabegron and imidafenacin. Although imidafenacin administration significantly increased the scores for dry mouth, blurred vision, and constipation, mirabegron administration did not. Mirabegron and imidafenacin have the same efficacy. Imidafenacin administration is associated with a higher rate of dry mouth, blurred vision, and constipation as compared to mirabegron administration. Neurourol. Urodynam. 36:1097-1103, 2017. © 2016 Wiley Periodicals, Inc.


Inhalation of odors containing DMHF generated by the Maillard reaction affects physiological parameters in rats.
The effects of odors generated by the Maillard reaction from amino acids and reducing sugars on physiological parameters (blood pressure, heart rate, and oxidative stress levels) in Wistar rats were investigated in the present study. The Maillard reaction samples were obtained from glycine, arginine, or lysine of 1.0 mol/L and glucose of 1.0 mol/L with heat treatment. The odor-active compounds in the Maillard reaction samples were identified using the aroma extract dilution analysis. Among the odor-active compounds identified, 2,5-dimethyl-4-hydroxy-3(2H)-furanone (DMHF, FURANEOL and strawberry furanone) had the highest odor activity and its concentration was affected by amino acid types. The Maillard reaction odors generated from glycine or arginine significantly decreased systolic blood pressure and heart rate in rats when inhaled. These physiological effects were associated with DMHF. Furthermore, oxidative stress marker levels in rat plasma were decreased by the inhalation of DMHF. The inhalation of DMHF appears to at least partly affect physiological parameters by decreasing oxidative stress.


Simulation study on dynamic characteristics of gas diffusion in coal under nitrogen injection.
To reveal the mechanism of desorption of methane in coal seams by inert gas N2, the desorption behavior of CH4 after N2 injection was studied by using Giant Canonical ensemble Monte Carlo (GCMC) and Molecular Dynamics (MD) methods with wiser bituminous coal as the research object. The results show that the adsorption isotherms of CH4 and N2 in the molecular structure model of bituminous coal are in good agreement with the Langmuir adsorption isotherm model. The adsorption capacity of the two gases in the bituminous coal structure model is CH4 > N2. The higher the N2 injection pressure, the higher the temperature, and the more methane desorption. N2 can replace some adsorbed CH4 through competitive adsorption with CH4. Compared with injecting high-temperature nitrogen to desorb methane in coal seams, in high-pressure nitrogen, the diffusion effect of CH4 flowing in coal is more significant. The higher the nitrogen injection pressure, the better the effect of N2 promoting CH4 desorption. The relative concentration of CH4 in the vacuum layer gradually increases with the increase of water content. This indicates that the water in coal promotes the desorption of CH4. The mechanism of N2 injection and CH4 desorption in coal seams mainly includes gas displacement and gas dilution and diffusion. This study provides theoretical support for methane extraction technology in goaf.


Insulin binding by a cell line (HT 29) derived from human colonic cancer.
Insulin binding was demonstrated in cultured HT 29 cells originating from a human colon carcinoma. At 37 degrees and in complete medium, the binding of [125I]insulin (1-4x10-10M) reaches a maximum in 40 min and the cell associated radioactivity remains constant for at least 4 h. No degradation of the hormone is observed under these conditions. The binding is proportional to the number of cells and its pH optimum is 7.8. In the presence of excess insulin 50% of the [125I]insulin is dissociated from the complex after 10 min. At equilibrium, insulin binding is specific: proinsulin is 25 times less potent than native insulin in competing with [125I]insulin and related polypeptide hormones are inactive. Scatchard analysis indicates two classes of binding sites (1400 sites/cell of "high affinity" e.g. 4.7 x 108 M-1, and 20 000 sites of "low affinity" e.g. 4 x 107 M-1). The binding of insulin to this non-target cell shows the same kinetic characteristics and specificity as found for insulin in its target cells, except that HT 29 cells do not degrade the hormone. The problem of the correlation between insulin binding and a biological effect in these cells remains to be elucidated.


Streptozotocin diabetes protects against arrhythmias in rat isolated hearts: role of hypothyroidism.
We examined the contribution of hypothyroidism to streptozotocin diabetes-induced alterations in the arrhythmia susceptibility of ex vivo hearts to regional zero-flow ischaemia. Diabetic rats received either protamine zinc insulin (10 IU/kg/day, s.c.) or triiodothyronine (10 microg/kg/day, s.c.) for 8 weeks commencing 72 h after injection of streptozotocin (60 mg/kg, i.p.). Arrhythmias were determined in ex vivo Langendorff-perfused hearts, subjected to a 30-min main left coronary artery occlusion, followed by 30-min reperfusion. Serum free thyroxine concentrations, rectal temperature and ex vivo heart rate were significantly decreased in the 8-week diabetic group (P<0.001). These changes were prevented by administration of triiodothyronine or insulin. Ventricular fibrillation during reperfusion was abolished in hearts from diabetic rats. This protection was prevented by treatment with either triiodothyronine or insulin. Hearts from methimazole-hypothyroid rats also showed no ventricular fibrillation during reperfusion. The protection against ischaemia-reperfusion-arrhythmias observed in hearts from streptozotocin-diabetic rats may be due to diabetes-induced hypothyroidism.


Smallpox vaccine stability after maintenance at temperatures not recommended for shipping.
Two distinct smallpox vaccine formulations were exposed to temperatures beyond the ranges specified by the manufacturers for vaccine maintenance and shipping. Under the conditions investigated, titers of both Dryvax smallpox vaccine and Aventis Pasteur smallpox vaccine remained at or above the titers recommended for successful vaccination. From these data it can be inferred that vaccine efficacy would not be expected to be adversely affected by unintended fluctuations of temperature, within the ranges studied, for a 4-day period.


Communication in the diagnostic mammography suite: implications for practice and training.
The diagnostic mammography suite is a microcosm of challenging physician-patient communication in radiology. Little has been written about communication practices in the diagnostic mammography suite, the effect of this communication on both physicians and patients, and implications for radiology training programs. We surveyed radiology residents and staff about communication training, practices, and experiences communicating directly with patients in the diagnostic mammography suite. We asked the membership of the Association of Program Directors in Radiology to disseminate surveys to radiology residents and staff radiologists in their institutions. We analyzed response frequencies and correlations. We received responses from 142 residents and 120 staff radiologists. More than half of staff respondents spoke personally with every patient who had an abnormal diagnostic mammogram; 37% felt they had inadequate time to do so. Most residents and staff highly rated their own communication skills and confidence in ability to explain results and respond to patients' emotions, but experienced stress doing so. A majority of respondents reported no formal communication skills education after medical school. Twenty-nine percent of staff respondents regularly observed residents' communication with patients and 39% of residents reported receiving feedback about their communication. Residents' opportunities to observe staff communicate with a patient and to receive feedback on their own patient interactions were correlated with self-rated communication skill and confidence in ability to respond to patients' emotions (P < .05). Radiologists engage in challenging and stressful patient communication interactions. There is a paucity of educational curricula on interpersonal and communication skills in radiology. This has implications for both patient and physician satisfaction and patient outcomes.


Drug abuse in athletes. Anabolic steroids and human growth hormone. Council on Scientific Affairs.
This report, the first in a three-part series on drug abuse by athletes, responds to adopted Resolution 4 (1984 Annual Meeting) and to Resolution 57 (1986 Annual Meeting), "Human Growth Hormone," which was referred to the Board of Trustees for action. Subsequent reports will cover other classes of abused drugs.


RNAi-mediated downregulation of CDKL1 inhibits growth and colony-formation ability, promotes apoptosis of human melanoma cells.
Cyclin-dependent kinase-like 1 (CDKL1) is a member of cell division control protein 2 (CDC-2)-related serine threonine protein kinase family, and is reported to be overexpressed in malignant tumors such as breast cancer and gastric cancer. This study aimed to evaluate the whether CDKL1 can serve as a potential molecular target for melanoma gene therapy. CDKL1 expression in two melanoma cell lines, A375 and MV3 was measured by real-time PCR. To investigate the role of CDKL1 in cell growth of melanoma, we constructed CDKL1-siRNA expressing lentivirus and infected A375 and MV3 cells. The effects of RNAi-mediated CDKL1 downregulation on A375 and MV3 cell proliferation and colony-formation ability were detected by methylthiazoletetrazolium (MTT) assay and colony-formation assay. The effects of CDKL1 downregulation on A375 and MV3 cell cycle and apoptosis were analyzed by FACS analysis. Human melanoma cell lines A375 and MV3 expressed CDKL1 mRNA. Knockdown of CDKL1 in A375 and MV3 by CDKL1-siRNA lentivirus infection significantly inhibited cell growth and colony formation ability, promoted cell apoptosis, and arrested cells in G1 phase. CDKL1 is associated with melanoma cell growth, colony formation, apoptosis, and cell cycle regulation. It may be considered as a valuable target for anti-melanoma therapeutic strategies.


Expanded use of sodium-glucose cotransporter 2 inhibitors: Evidence beyond heart failure with reduced ejection fraction.
Following the results observed in the DAPA-HF trial and subsequent FDA approval of dapagliflozin in patients living with heart failure with reduced ejection fraction (HFrEF), numerous trials quickly began to assess the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in a wide range of cardiovascular (CV) conditions. Since the publication of those findings, multiple SGLT2i have demonstrated benefit in patients regardless of left ventricular ejection fraction (LVEF)-allowing the drug class to establish itself within the first line of guideline-directed medication therapy. Although the full mechanistic properties of SGLT2i in heart failure (HF) have yet to be fully understood, benefits in other disease states have continued to emerge over the past decade. This review summarizes the findings of 14 clinical trials investigating the use of SGLT2i in various CV disease states, with a special focus on HF with preserved ejection fraction (HFpEF) and acute decompensated HF (ADHF). Additionally, studies assessing the CV-related mechanisms, cost-effectiveness, and exploratory effects of dual SGLT1/2 blockade are described. A review of select ongoing trials has also been incorporated to further characterize the research landscape with this medication class. The aim of this review is to serve as a comprehensive tool for healthcare providers to better understand how this class of diabetes medications established its place in the treatment of HF.


Relative increase in apolipoprotein CII content of VLDL and chylomicrons in a case with massive type V hyperlipoproteinaemia by nicotinic acid treatment.
VLDL of fasting serum was fractionated into 4 fractions of decreasing particle size by preparative ultracentrifugation in a density gradient from a patient with massive type V hyperlipoproteinaemia before and after treatment with 12 g daily of nicotinic acid. Serum triglycerides fell from 58 to 9 mmol/1 in response to treatment due particularly to reduction of larger VLDL particles. Total, insoluble (apoprotein B) and soluble protein of all VLDL fractions also fell but the ratio of these 3 protein fractions to triglyceride rose particularly in the smaller VLDL fractions. The relative amount of apolipoprotein CII increased in all fractions and the ratio apo CII to triglycerides increased by 60--90% in all VLDL fractions. The relative amounts of apo CI, apo CII-2 and apo E appeared also to increase. The results are consistent with the hypothesis that low amounts of apo CII may play a role for the development of hypertriglyceridaemia.


A generative tool for building health applications driven by ISO 13606 archetypes.
The use of Electronic Healthcare Records (EHR) standards in the development of healthcare applications is crucial for achieving the semantic interoperability of clinical information. Advanced EHR standards make use of the dual model architecture, which provides a solution for clinical interoperability based on the separation of the information and knowledge. However, the impact of such standards is biased by the limited availability of tools that facilitate their usage and practical implementation. In this paper, we present an approach for the automatic generation of clinical applications for the ISO 13606 EHR standard, which is based on the dual model architecture. This generator has been generically designed, so it can be easily adapted to other dual model standards and can generate applications for multiple technological platforms. Such good properties are based on the combination of standards for the representation of generic user interfaces and model-driven engineering techniques.


Corticotropin-releasing hormone receptor 1 coexists with endothelin-1 and modulates its mRNA expression and release in rat paraventricular nucleus during hypoxia.
To determine whether corticotropin-releasing hormone receptor 1 (CRHR1) coexists with endothelin-1 (ET-1) in rat paraventricular nucleus (PVN), ET-1 expression and its regulation by CRH and CRHR1 under hypoxia, rats were exposed to simulated continuous hypoxia at 5 km altitude (CH5km, equal to 10.8% O(2)) in a hypobaric chamber for 1, 2, 5, 10, 15 or 25 days. ET-1, CRH, and its mRNA were measured using radioimmunoassay (RIA), immunohistochemistry, and in situ hybridization. The coexistence of ET-1 and CRHR1 was identified by confocal immunofluorescence. The results showed that CH5km caused a significant decrease of ET-1 level in PVN at 5 days, but decreased CRH on days 1 and 2 while it increased on days 5 and 10. CH5km induced ET-1 mRNA upregulation and ET-1 decrease at 5 days, the effects were completely reversed by treatment with five-daily-injections of a CRHR1 antagonist (butyl-[2,5-dimethyl-7-(2,4,6-trimethylphenyl)-7H-pyrrolo[2,3-d] pyrimidin-4-yl]-ethylamine: CP-154,526). Also, this treatment significantly reversed the CH5km-induced increase in CRH and CRHmRNA in PVN at 5 days. Moreover we found that the changes in expression of ET-1 and CRHR1 induced by CH5km were co-localized in parvocellular PVN cells. In conclusion, CRHR1 coexists with ET-1 in parvocellular PVN, continuous hypoxia stimulates ET-1 and ET-1mRNA as well as CRH and CRHmRNA, and CRHR1 evidently modulates ET-1 release and ET-1mRNA activation caused by continuous hypoxia.


Assessing occupational stress in psychiatric nurses using the full job strain model: the value of social support to nurses.
The present research examined the effects of occupational stress in psychiatric nursing on employee well-being using the full Job Strain Model. The Job Strain Model was assessed for its ability to predict employee well-being in terms of job satisfaction and mental health. The original Job Strain Model was expanded to include social support based on previous research concerning the impact of social support on well-being. In the present study, both work support and non-work were assessed for their contribution to well-being. The results of this study indicate that the full Job Strain Model can be used to significantly predict job satisfaction and mental health in this sample of Australian psychiatric nurses. Furthermore, social support was shown to be an important component of the Job Strain Model.


Increased Bcl-xL expression mediates v-Src-induced resistance to anoikis in intestinal epithelial cells.
Acquisition of resistance to anoikis (detachment-induced apoptosis) is considered to be a requirement for transformed intestinal epithelial cells to invade surrounding tissues and metastasize to distant organs. Increased Src kinase activity, which is a feature of a large proportion of colorectal cancers, has been identified as one of the factors that can contribute to anoikis resistance. However, the molecular mechanism by which high levels of Src activity contribute to anoikis resistance in intestinal epithelial cells is unknown. Here we show that high Src activity confers resistance to anoikis in intestinal epithelial cells, at least in part, by inducing Bcl-xL overexpression, and that this induction is mediated by the MEK/MAPK pathway. Based on the findings reported here, and on our previous study showing that Bcl-xL plays a critical role in ras-induced resistance to anoikis, we propose that the increased Bcl-xL levels found in colorectal cancers play a significant role in the induction of resistance to anoikis during the progression of this disease.


Fluorescence-Based Measurements of the CRAC Channel Activity in Cell Populations.
Cytosolic Ca2+ plays an important role in cellular biology, and since its identification as a second messenger, a number of techniques and methods to analyze the changes in cytosolic Ca2+ concentration ([Ca2+]c) induced by physiological agonists have been developed. Changes in [Ca2+]c might be determined in single cells or in cell populations. Measurement in single cells allows to determine changes in [Ca2+]c at a subcellular level but often results in heterogeneous responses among cells. Determination of intracellular Ca2+ mobilization at the cell population level reduces this heterogeneity and allows [Ca2+]c measurements in small cells that load little amounts of indicator. Here, we describe the measurement of agonist-evoked changes in [Ca2+]c associated with Ca2+ influx in cell populations.


Activation of spinal extracellular signaling-regulated kinase-1 and -2 by intraplantar carrageenan in rodents.
We have examined the activation of spinal extracellular signaling-regulated kinase (ERK) in juvenile rats and adult mice after intraplantar carrageenan or saline and its relationship to pain behavior. In rats, intraplantar carrageenan evoked a peak five-fold activation of spinal ERK at 30 min measured by immunoblot. Saline injection resulted in a two-fold activation. This differential ERK activation correlated with a 2.5-fold greater pain response and the development of secondary hyperalgesia in carrageenan-injected rats, whereas both saline and carrageenan produced similar primary hyperalgesia. In mice, carrageenan injection produced a peak 3.5-fold activation of ERK, but saline was ineffective. We conclude that ERK activation may underlie spinal nociceptive processing and secondary hyperalgesia after carrageenan inflammation.


Diagnosis and differentiation of mature cystic teratoma of pancreas from its mimics: A case report.
Mature cystic teratoma originating in the pancreas is very unusual, often observed as an incidental finding during routine examinations or recognized perioperatively as the patients present with very unspecific clinical symptoms. The confirmatory diagnosis of a pancreatic cystic teratoma is generally made by histopathology after surgical excision. So, the preoperative diagnosis is very challenging, especially differentiation from the other pancreatic pathologies. A 23-year-old woman was admitted to our hospital with a complaint of mild grade periumbilical abdominal pain. A pancreatic mass was revealed on a preliminary abdominal ultrasound examination. Her medical history was unremarkable with no long-standing illness or malignancy. Mature cystic teratoma in the head of the pancreas. Roux-enY choledochojejunostomy with gastrojejunostomy was performed, excising the tumor from the pancreatic head. The postoperative course was uneventful; the patient was asymptomatic and has no evidence of recurrence on a 2-year follow up. Pancreatic cystic teratoma is a benign, well-differentiated, and extremely rare congenital tumor. MRI is the choice of imaging modality and phase-GRE or fat suppression is the best technique for pre-operative diagnosis.


Morphological characteristics of lateral pelvic lymph nodes in locally advanced lower rectal cancer: A retrospective study.
This study aimed to investigate the potential of the size and aspect ratio of metastatic and non-metastatic lateral pelvic lymph nodes (LPLNs) as low-risk markers for locally advanced lower rectal cancer, without treatment by neoadjuvant chemoradiation therapy or LPLN dissection. This single-center, retrospective cohort study evaluated 310 consecutive patients diagnosed with lower rectal cancer (T: T3/T4, N: any, and M: M0) who underwent curative surgery without neoadjuvant therapies between 2010 and 2018. The harvested LPLNs were categorized into groups A (metastasis-positive lymph nodes), B (metastasis-negative lymph nodes in the area bearing metastasis-positive lymph nodes), C (metastasis-negative lymph nodes in a metastasis-negative area in metastasis-positive patients), and D (lymph nodes in non-metastatic patients). The main outcome measure was the relationship among lymph node size, aspect ratio, and metastasis in the LPLNs. Overall, 3962 LPLNs were harvested. The long and short axes and the aspect ratio were significantly longer and higher, respectively, in group A than in the other groups (P < .001). The aspect ratio in group B was significantly higher than that in groups C and D (P < .001). The aspect ratio in group C was significantly higher than that in group D (P < .001). Furthermore, no metastasis-positive lymph nodes had an aspect ratio of less than 0.4. Metastasis-positive LPLNs tended to be larger and rounder than their metastasis-negative counterparts. Metastatic LPLNs in patients with lower rectal cancer are significantly larger and have a higher aspect ratio. Lymph nodes with aspect ratios of <0.4 were metastasis negative.


A Prospective Study of a Resorbable Intravesical Fiducial Marker for Bladder Cancer Radiation Therapy.
We conducted a prospective pilot study to evaluate safety and feasibility of TraceIT, a resorbable radiopaque hydrogel, to improve image guidance for bladder cancer radiation therapy (RT). Patients with muscle invasive bladder cancer receiving definitive RT were eligible. TraceIT was injected intravesically around the tumor bed during maximal transurethral resection of bladder tumor. The primary endpoint was the difference between radiation treatment planning margin on daily cone beam computed tomography based on alignment to TraceIT versus standard-of-care pelvic bone anatomy. The Van Herk margin formula was used to determine the optimal planning target volume margin. TraceIT visibility, recurrence rates, and survival were estimated by Kaplan-Meier method. Toxicity was measured by Common Terminology Criteria for Adverse Events version 4.03. The trial was fully accrued and 15 patients were analyzed. TraceIT was injected in 4 sites/patient (range, 4-6). Overall, 94% (95% confidence interval [CI], 90%-98%) of injection sites were radiographically visible at RT initiation versus 71% (95% CI, 62%-81%) at RT completion. The median duration of radiographic visibility for injection sites was 106 days (95% CI, 104-113). Most patients were treated with a standard split-course approach with initial pelvic radiation fields, then midcourse repeat transurethral resection of bladder tumor followed by bladder tumor bed boost fields, and 14/15 received concurrent chemotherapy. Alignment to fiducials could allow for reduced planning target volume margins (0.67 vs 1.56 cm) for the initial phase of RT, but not for the boost (1.01 vs 0.96 cm). This allowed for improved target coverage (D95% 80%-83% to 91%-94%) for 2 patients retrospectively planned with both volumetric-modulated arc therapy and 3-dimensional conformal RT. At median follow-up of 22 months, no acute or late complications attributable to TraceIT placement occurred. No patients required salvage cystectomy. TraceIT intravesical fiducial placement is safe and feasible and may facilitate tumor bed delineation and targeting in patients undergoing RT for localized muscle invasive bladder cancer. Improved image guided treatment may facilitate strategies to improve local control and minimize toxicity.


Recurrent urinary tract infections in kidney transplant recipients.
Urinary tract infection (UTI) constitutes the most frequent infection among kidney transplantation (KT) patients. The epidemiology and specific risk factors for recurrent UTI after KT have not been well studied. The aim of this work was to assess the incidence, pathogenic spectrum, and risk factors for recurrent post-KT UTI. This observational, cross-sectional study included all patients admitted to our transplantation department with a diagnosis of post-KT UTI from January 2010 to December 2011. Recurring post-KT UTI was defined as ≥ 2 UTIs in 6 months or ≥ 3 UTIs in 12 months. Factors associated with recurrent post-KT UTI were assessed using logistic regression analysis. The 154 patients were diagnosed with 315 episodes of post-KT UTI (28.6%), with recurrent post-KT UTI among 72% of cases. Most recurrent UTIs (73.6%) occurred during the first year after KT. Klebsiella species was the most common isolated pathogen (53.2%), being a serious problem for multidrug-resistance (odds ratio [OR], 13; 95% confidence interval [CI] 5.9-28.6; P < .001). The presence of nosocomial infection (OR, 2.8; 95% CI, 1.4-5.4; P < .003) and multidrug-resistant bacteria (OR, 3.8; 95% CI, 2-7.2; P < .001) emerged as independent predictors of recurrent post-KT UTI. KT recipient demographics and characteristics, factors related to KT and urologic complications, did not differ significantly between patients with versus without recurrent post-KT UTI. In conclusion, in a unit where recurrent post-KT UTI incidence was 72% and Klebsiella species was the prevailing uropathogen, nosocomial infection and multidrug-resistant bacteria appeared to be independent predictive factors for recurrent post-KT UTI.


Receptive fields of neurons in areas 17 and 18 of tree shrews (Tupaia glis).
Receptive fields of 245 cells in areas 17 and 18 were explored in tree shrews. Cells with simple and complex receptive fields were found in both areas but with different statistical distriubtions. A small percentage of non-oriented fields were found to be binocularly activated in both areas. Cells in area 17 preferred dark over light stimuli. Selective for direction, speed of stimulus movement, and level of background illumination, as well as combinations of these were common. Few hypercomplex cells were found. The superior retention of visually guided behavior of three shrews after lesions of the striate cortex is not explained by any radical difference between the properties of their striate neurons and those of other mammals.


Venom immunotherapy during COVID-19 pandemic: Experience from a University Allergy Center in Northern Italy.
During the ongoing pandemic of Coronavirus Disease 2019 (COVID-19) allergic patients need to continue their constant and proper treatment, including allergen-specific immunotherapy. These patients are expected to be at a higher risk for exacerbation of lung inflammation during viral infection. We investigated the putative interplay existing between allergen-specific immunotherapy and COVID-19 infection in a Hymenoptera venom-allergic population. We evaluated the frequency and severity of COVID-19 infection in a cohort of 211 subjects referring to our center for the regular administration of venom immunotherapy (VIT). Our result showed that the median age of our cohort is similar to the one that in our region has been associated with a high incidence of COVID-19 infection, increased hospitalization, and mortality rates. We reported only an isolated positivity of COVID-19 in the overall group; whereas none suffered from upper airway symptoms associated with COVID-19 (fever, cough, dyspnoea, sore throat, anosmia, and/or ageusia). Even though the demographic characteristics pose a substantial risk for such a population, we suggest that a regular administration of VIT may help in the development of an immunological milieu able to down modulate the Th1/Th17 environment that has been linked to inflammatory manifestations of COVID-19. To the best of our knowledge, this is the first description of the incidence of COVID-19 infection in Hymenoptera venom allergic patients treated with VIT, suggesting indirectly that venom immune tolerance-inducing treatment may be capable of reducing the aberrant inflammatory response induced by the virus in this specific population.


Modulation of adriamycin transport by hyperthermia as measured by fluorescence-activated cell sorting.
Heat-induced (45.5 degrees C) modification of adriamycin uptake and efflux were measured by flow cytometry in CHO cells in vitro. Administration of adriamycin with simultaneous 15-min or 30-min heat treatment increased drug uptake in a dose-dependent manner. Fluorescence-activated cell sorting showed that cytotoxicity to adriamycin was correlated with relative cellular concentration (fluorescence) for both unheated cells and those heated and simultaneously treated with adriamycin. However, if adriamycin administration followed the heat treatment, accumulation was significantly reduced, primarily as a result of decreased passive drug diffusion (rather than increased efflux) in the heated cells. Cells made heat-tolerant by prior heating also exhibited reduced adriamycin uptake 12 h later, and further heating did not increase uptake. Cell sorting experiments indicated that cytotoxicity of adriamycin was not necessarily correlated with intracellular drug levels when drug administration followed the heat treatment. Also, heat-sterilized cells exhibited a two-fold increase in adriamycin uptake over surviving cells, as assessed by simultaneous measurement of dansyl lysine and adriamycin content. These results indicate that sensitization to adriamycin by simultaneous heat treatment is probably due to increased drug uptake. The decreased sensitization observed when drug administration is followed by heating is probably the result of both decreased uptake and decreased drug DNA accessibility.


The differential effect of maternal dietary patterns on quantiles of Birthweight.
Maternal dietary habits during pregnancy are considered essential for development and growth of the fetus as well as maternal health. It has an effect on the birthweight of infants. However, little is known about the effect of dietary patterns on birthweight in urban South Africa. This study aimed to investigate differential effect of dietary patterns of pregnant women on quantiles of birthweight. Data for the study were obtained from a Mother and Child in the Environment birth cohort study in Durban South Africa. Quantile regression was used to investigate the effect of maternal dietary patterns on quantiles of birthweight. Data collection was conducted during the period of 2013 to 2017 in Durban South Africa. Using factor analysis, eight dietary groups were identified from 687 pregnant women in the cohort. Quantile regression analysis was employed to identify the differential effects of the seven dietary groups and demographic factors on the birthweight. The quantile regression estimates at the 50th quantile and the ordinary regression estimates painted the same picture about the conditional mean effect of covariates on the birthweight. But unlike the quantile regression the ordinary regression fails to give insights about the covariates effect disparities at the low and/or upper birthweight quantiles. All the dietary groups show a significant differential effect at different birthweight quantiles. For instance, increased frequency of protein rich foods intake was associated with reduction in birthweight at lower and upper quantiles; increased frequency of junk foods intake has a slight increase in birthweight at the lower quantiles but significantly higher increase at the 95th quantile (p < 0.001); increase in consuming vegetable rich foods, reduced birthweight at 95th quantile (p < 0.001). The results further showed that employment (p = 0.006) and family size (p = 0.002) had differential effects across different birthweight quantiles. Both maternal undernutrition and overnutrition of protein rich foods, junk foods, snack and energy foods and vegetable rich foods have shown a substantial varying effects on those infants with birthweights in the lower and upper birthweight quantiles.


Correction of long term joint contractures of the hand by distraction. A case report.
Joint contractures are a common complication of hand trauma. The conventional treatment consists of arthrolysis, tenolysis and occasionally arthrodesis. Frequently, this does not achieve a good result, particularly when there has been a long delay in presentation. Progressive lengthening of a joint by distraction (joint distraction) allows the release of joint contractures even in cases of failure of traditional methods. We present a case of a delayed (20 years) work related traumatic flexion deformity of the PIP joint of the left index and middle fingers. This was the result of a complete division of both flexor tendons of both fingers. The range of movements, both active and passive, was limited to 90/100 degrees in the index finger and 95/100 degrees in the middle finger. Following joint distraction using our lengthening device (Antãotrade mark, Portugal) the patient was able to achieve an active and passive range of movements of 10/100 degrees for the PIP joint of the index finger and 40/100 degrees of the middle. This clinical case shows the simplicity and application of our technique for the correction of joint contractures.


Gentamicin solution for mediastinal irrigation: systemic absorption, bactericidal activity, and toxicity.
Local irrigation with gentamicin sulfate represents a possible substitute for neomycin sulfate, used for many years but now no longer available for use as an irrigation fluid. In this investigation, mediastinal irrigation with gentamicin was used in 12 patients who had experienced problems after a heart operation. The regimen employed for mediastinal irrigation with gentamicin was equipotent with that using neomycin. We sought to determine the degree of absorption and risk of either inadequate or toxic blood levels that might follow gentamicin absorption. Irrigation periods were short, ranging from one to four days and determined by measurements of plasma gentamicin concentration using radioimmunoassay evaluation. Systemic gentamicin absorption occurred in all patients. Toxic levels of higher than 8.0 micrograms/mL occurred and were size related, ie, correlated with smaller body weight and surface area, and sex related, ie, female sex. Larger-sized patients often had inadequate levels. Despite the potential risk from toxic blood levels, major increases in serum creatinine levels were not seen. These findings suggest that monitoring of plasma gentamicin levels during mediastinal irrigation with gentamicin is mandatory to avoid both inadequate treatment and toxicity.


Direct observation of the rapid aggregation of acetylcholine receptors on identified cultured myotubes after exposure to embryonic brain extract.
We have directly observed the redistribution of acetylcholine receptors (AChR) on the surface of cultured myotubes, induced by a soluble brain extract. The AChR were fluorescently labeled with rhodamine-conjugated alpha-bungarotoxin and viewed under low incident illumination with a video image intensification system. The results of our sequential observations indicate that AChR aggregates can be assembled rapidly (30-120 min) from mobile, diffuse AChR. This assembly was characterized by the initial formation of microaggregates (less than 1 micron diameter) that increased in number and coalesced or grew to form larger aggregates. The redistribution of fluorescently labeled AChR was completely inhibited by illumination of cells at levels used for conventional fluorescence micrography and could be observed only by using low light levels.


Increasing collective efficacy for physical activity: Design and rationale of Moms UNITE for Health.
Mothers are a population that engages in low levels of physical activity due to unique barriers to physical activity. As such, there is a need to develop and implement physical activity interventions for mothers that can be delivered in community settings. The objective of this article is to describe the Moms UNITE (Using Networks to Increase Togetherness and Efficacy) for Health walking intervention. This intervention, based on social cognitive theory, is designed to compare a collective efficacy enhanced intervention to a standard intervention for increasing physical activity and secondary outcomes. In this 6-week, randomized controlled trial, mothers will be assigned to either the standard or intervention (collective efficacy) group. Both groups will receive the same walking intervention and an evidence-based health education program. Strategies and messages focusing on building collective efficacy will be used in the intervention group. Data will be collected at baseline, post-intervention, and follow-up (after a 3 month no-intervention period) using a mixed methods approach. Quantitative data will include anthropometric measurements, objective physical activity, and questionnaires assessing self- and collective-efficacy. Post-intervention focus groups and weekly process evaluation surveys will describe participants' experiences within the program. This paper will serve as a theoretical framework for researchers and public health practitioners to develop and implement community-based walking programs for mothers.


The effect of peripheral blood contamination on colony yield from human bone marrow aspirates.
Serial bone marrow aspirates were taken from a single site in each of nine individuals. The colony forming capacity of these samples, measured by culturing the cells in semi-solid agar in diffusion chambers, fell as the aspirate volume increased. Comparison of the results from different individuals showed that this effect was consistent within the group and may be useful as a simple method for standardizing results from human bone marrow cultures.


High-BMI at diagnosis is associated with inferior survival in patients with osteosarcoma: a report from the Children's Oncology Group.
Body mass index (BMI), at diagnosis has been associated with lower survival and increased toxicity in cancer patients. We analyzed the effect of BMI at diagnosis on therapy related toxicities and outcome in pediatric osteosarcoma patients treated on Children's Oncology Group (COG) trial INT0133. All patients enrolled on COG-INT0133 with height, weight and toxicity information were eligible. BMI was expressed as age and gender specific percentiles using height and weight at diagnosis. Patients were classified into high, normal and low BMI groups. Logistic regression models were used to analyze toxicities; Kaplan-Meier curves were created to assess event free (EFS) and overall survival (OAS). Seven hundred and ten patients met eligibility criteria. BMI distribution was: 447 normal BMI, 74 low BMI, and 189 high BMI. Renal toxicity was higher in the high BMI group (OR = 2.7, 95% CI 1.2-6.4, P = = 0.01) only during one of the courses of therapy. Compared to the normal BMI group, patients with high BMI had significantly worse OAS at 5 years compared to those with normal BMI, 69.7% versus 80.5% (HR = 1.6, 95% CI 1.1-2.2, P = 0.005) and a trend towards worse event-free survival at 3 years 66.2% versus 75.5% (HR = 1.3 95% CI 0.9-1.8, P = 0.05). There was no difference in EFS or OAS in patients with low BMI compared to patients with normal BMI. High BMI at diagnosis is associated with worse OAS in patients with osteosarcoma. No clinically significant differences in toxicity were observed in the various BMI groups.


Evaluation and monitoring of patients with acute heart failure syndromes.
Advanced heart failure (HF) is associated with frequent hospitalizations, poor quality of life, and increased mortality. Despite optimal medical management, readmission rates remain high and account for approximately two thirds of all costs related to HF management. Evaluation of patients with HF is critical for the appropriate selection and monitoring of therapy as well as for the prevention of recurrent hospitalizations. This evaluation can be complex and relies on integration of the bedside evaluation and information available from invasive and other noninvasive diagnostic techniques. The clinical examination remains the cornerstone of HF evaluation. Key features of the history and physical examination can be used to assign hemodynamic profiles based on the absence or presence of congestion and adequacy of perfusion. These hemodynamic profiles provide prognostic information and may be used to guide therapy. Direct measurement of hemodynamics may be helpful in patients in whom the physical examination is limited or discordant with symptoms. Although the pulmonary artery catheter (PAC) is not recommended during routine therapy of patients hospitalized with HF, it is reasonable to consider the use of PAC monitoring to adjust therapy in patients who demonstrate recurrent or refractory symptoms despite ongoing standard therapy adjusted according to clinical assessment. This is particularly relevant in centers with experience in hemodynamic monitoring for HF. B-type natriuretic peptide (BNP) testing has been shown to facilitate diagnosis of the etiology of dyspnea in the urgent setting for patients without a prior diagnosis of HF. Furthermore, BNP levels provide important prognostic information in patients with chronic HF, but serial BNP testing has not been validated as a guide to inpatient or outpatient management. Echocardiographic assessment can provide prognostic information about ventricular function and size as well as information about hemodynamic status. Development of validated and reproducible noninvasive techniques to monitor patients with acute HF will be an important step in maximizing interventions to improve outcomes in this patient population.


Incidence of inflammatory bowel disease in the province of Styria, Austria, from 1997 to 2007: a population-based study.
The incidence of inflammatory bowel disease (IBD) varies widely between different countries. This large variation is also observed for the incidence of its main two forms, ulcerative colitis (UC) and Crohn's disease (CD). Controversy exists whether IBD incidence is increasing, especially in western countries. Currently no data are available for Austria. This study therefore aimed to evaluate for the first time the incidence of IBD over an eleven-year period in Styria, a province of Austria with a population of 1.2 million. All patients with an initial diagnosis of IBD between 1997 and 2007, who were Styrian residents, were eligible for this retrospective study. Data were acquired from electronically stored hospital discharge reports and individual reports by patients and physicians. According to population density Styria was divided into two rural and one urban area. Throughout the study period 1527 patients with an initial diagnosis of IBD were identified. The average annual incidence was 6.7 (95% CI 6.2-7.1) per 100,000 persons per year for CD and 4.8 (95% CI 4.5-5.2) for UC. The average annual incidence increased significantly (p<0.01) for both diseases during the 11 year study period. Median age at initial diagnosis was 29 years (range 3-87) for CD and 39 years (range 3-94) for UC. At diagnosis, 8.5% of all IBD patients were <18 years of age. The incidence of both CD and UC was significantly higher in the urban area than in rural areas (CD: 8.8, 95% CI 7.8-9.8 versus 5.5, 95% CI 4.7-6.4 and 5.9, 95% CI 5.3-6.7; [p<0.001]; UC: 5.8, 95% CI 5.1-6.6 versus 4.0, 95% CI 3.4-4.7 and 4.7, 95% CI 4.1-5.4; [p=0.04]). We observed an overall increase in the incidence of ulcerative colitis and Crohn's disease in a part of Austria during an eleven year period. IBD was more predominant in the largest urban area than in rural areas.


Arachnoid Membranes: Crawling Back into Radiologic Consciousness.
The arachnoid membranes are projections of connective tissue in the subarachnoid space that connect the arachnoid mater to the pia mater. These are underappreciated and largely unrecognized by most neuroradiologists despite being found to be increasingly important in the pathogenesis, imaging, and treatment of communicating hydrocephalus. This review aims to provide neuroradiologists with an overview of the history, embryology, histology, anatomy, and normal imaging appearance of these membranes, as well as some examples of their clinical importance.


Cytotoxicity and induction of protective mechanisms in HepG2 cells exposed to cadmium.
Cadmium is a widespread industrial pollutant. The primary route of exposure occurs via contaminated drinking water or food supplies, and tobacco. Its chronic introduction and ingestion lead to bio-magnification in target organs, as the liver. The aim of this paper is to determine Cd cytotoxic concentrations in the human hepatoma cell line HepG2. Further aims are the study of the activation and involvement of protection mechanisms against Cd hepatotoxicity. Cd was accumulated within the cells, as measured by ICP-AES. Metallothioneins (MT-1 and -2), a family of metal-binding proteins, were induced in a dose-dependent way after treatment with concentrations below the IC(50) value (mean value 22 microM). The over-expression of MT by Zn pre-treatment was able to defend against Cd cytotoxicity. Heat shock protein 70 kDa (hsp70) was induced at high non-cytotoxic concentrations (5, 10 microM) probably as a consequence of proteotoxicity, but its over-expression by a sub-lethal heat shock was not able to protect the cells from Cd cytotoxic concentrations (20, 50, 100 microM).


Cone-beam CT-guided radiotherapy in the management of lung cancer: Diagnostic and therapeutic value.
Recent studies have demonstrated an increase in the necessity of adaptive planning over the course of lung cancer radiation therapy (RT) treatment. In this study, we evaluated intrathoracic changes detected by cone-beam CT (CBCT) in lung cancer patients during RT. A total of 71 lung cancer patients treated with fractionated CBCT-guided RT were evaluated. Intrathoracic changes and plan adaptation priority (AP) scores were compared between small cell lung cancer (SCLC, n = 13) and non-small cell lung cancer (NSCLC, n = 58) patients. The median cumulative radiation dose administered was 54 Gy (range 30-72 Gy) and the median fraction dose was 1.8 Gy (range 1.8-3.0 Gy). All patients were subjected to a CBCT scan at least weekly (range 1-5/week). We observed intrathoracic changes in 83 % of the patients over the course of RT [58 % (41/71) regression, 17 % (12/71) progression, 20 % (14/71) atelectasis, 25 % (18/71) pleural effusion, 13 % (9/71) infiltrative changes, and 10 % (7/71) anatomical shift]. Nearly half, 45 % (32/71), of the patients had one intrathoracic soft tissue change, 22.5 % (16/71) had two, and three or more changes were observed in 15.5 % (11/71) of the patients. Plan modifications were performed in 60 % (43/71) of the patients. Visual volume reduction did correlate with the number of CBCT scans acquired (r = 0.313, p = 0.046) and with the timing of chemotherapy administration (r = 0.385, p = 0.013). Weekly CBCT monitoring provides an adaptation advantage in patients with lung cancer. In this study, the monitoring allowed for plan adaptations due to tumor volume changes and to other anatomical changes.


Oxygen free radicals and lungs.
Some of the metabolites resulting from the monovalent reduction of O2, superoxide anion and hydroxyl radical, are O2, radicals, whereas H2O2, which is not a radical since having no unpaired electron, is also an active O2 intermediate. These O2 metabolites are formed intracellularly as a result of normal metabolism. Their production can increase following exposure to high O2 concentration, radiations or certain drugs. An increased amount of extracellular O2 metabolites occurs after activation of certain inflammatory cells or during the course of the hypoxanthine-xanthine oxidase reaction. To counteract this oxidative stress, antioxidant defenses exist, whether enzymatic (superoxide dismutase, glutathione peroxidase, catalase, etc.) or nonenzymatic (GSH, vitamin E and C, etc.). Oxidative injury can result from an imbalance between oxidative stress and the defense mechanisms. The main targets are protein, DNA and lipids. The cellular response of the lung is stereotyped and involves cell injury (especially endothelial cells and type I pneumocytes), inflammatory reaction and repair processes.


Mast cells in the Harderian gland of female Syrian hamsters during the estrous cycle and pregnancy: effects of the light/dark cycle.
The number of identifiable mast cells and the intraluminal area occupied by porphyrin deposits was studied on semithin sections from female hamster Harderian glands during the estrous cycle and pregnancy. Although the serum levels of estradiol, progesterone, luteinizing hormone and follicle stimulating hormone exhibited significant changes throughout the cycle, no correlation between these changes and the variations in the number of recognizable mast cells was observed. However both during diestrous 1 and proestrous cycles, the number of identifiable mast cells was higher at midnight than at noon (in 14 h light:10 h dark photoperiod with lights on at 07:00 h). A more exhaustive study revealed the presence of 'degranulated mast cells' which were not stained with toluidine blue. Thus, a diurnal cycle in degranulation might occur in the Harderian glands from female hamsters. No significant variations were observed in the area occupied by intraluminal porphyrin deposits during the estrous cycle. However, both the relative number of mast cells and the area occupied by intraluminal porphyrins decreased from day 4 of pregnancy to day 14 showing a strong correlation. The Harderian glands from female Syrian hamsters might provide a useful model for the study of mast cell degranulation during porphyria.


Study on Factors That Influence Human Errors: Focused on Cabin Crew.
This study aims to reduce the possibility of human mistakes and accidents among airline cabin crew by identifying the cause of human errors by focusing on the importance of the causal relationship between human factors and human errors. According to statistical analysis, among the five human factors, physical fatigue, psychological stress, and the complacency of cabin crew had a positive impact on human errors. However, hurrying under time pressure and the distractions caused by external factors do not significantly affect human errors. Human errors have a negative impact on job crafting and mental health. This study analyzed the human factors influencing the cabin crew's errors and revealed the importance of complacency, which was not covered in previous studies. Finally, the research implications, limitations, and future studies were discussed.


Analysis and characterization of the genes encoding the Dicer and Argonaute proteins of Schistosoma japonicum.
The Dicer and Argonaute(AGO) proteins within the small RNA regulatory pathways (SRRPs) play an indispensable role in regulation of gene expression. In this study, we analyzed two genes, Dicer and Argonaute, from Schistosoma japonicum, along with their expression through a combination of bioinformatics and experimental approaches. Our results indicate that one Dicer and four Argonaute genes exist in Schistosoma japonicum, termed SjDicer and SjAGO1, 2, 3, and 4, respectively. SjDicer encodes 2590 amino acid residues that contains 5 conserved domains, including one amino-terminal helicase domain, one PAZ (Piwi-Argonaut-Zwille) domain, two RNAse III domains, and one dsRNA-binding domain. SjAGO1, 2, and 3 encode 1009, 945, and 904 amino acid residues, respectively, all of which contain PAZ and PIWI domains. In addition, we analyzed the expression profiles of SjDicer and SjAGO1 genes by qRT-PCR in eggs, miracidium, cercariae, schistosomula, and adult worms. Results showed consistent expression of both SjDicer and SjAGO1 in different stages; however, their expression levels were stage-dependent, with the highest being in the miracidium stage. This study provided the sequence of the Dicer and Ago genes of S. japonicum and their expression profiles which are essential for further investigation of functions of miRNA in Schistosoma japonicum.


Exploring novel hormones essential for seawater adaptation in teleost fish.
Marine fish are dehydrated in hyperosmotic seawater (SW), but maintain water balance by drinking surrounding SW if they are capable of excreting the excess ions, particularly Na(+) and Cl(-), absorbed with water by the intestine. An integrative approach is essential for understanding the mechanisms for SW adaptation, in which hormones play pivotal roles. Comparative genomic analyses have shown that hormones that have Na(+)-extruding and vasodepressor properties are greatly diversified in teleost fish. Physiological studies at molecular to organismal levels have revealed that these diversified hormones are much more potent and efficacious in teleost fish than in mammals and are important for survival in SW and for maintenance of low arterial pressure in a gravity-free aquatic environment. This is typified by the natriuretic peptide (NP) family, which is diversified into seven members (ANP, BNP, VNP and CNP1, 2, 3 and 4) and exerts potent hyponatremic and vasodepressor actions in marine fish. Another example is the guanylin family, which consists of three paralogs (guanylin, uroguanylin and renoguanylin), and stimulates Cl(-) secretion into the intestinal lumen and activates the absorptive-type Na-K-2Cl cotransporter by local luminocrine actions. The most recent addition is the adrenomedullin (AM) family, which has five members (AM1, 2, 3, 4 and 5), with AM2 and AM5 showing the most potent or efficacious vasodepressor and osmoregulatory effects among known hormones in teleost fish. Accumulating evidence strongly indicates that members of these diversified hormone families play essential roles in SW adaptation in teleost fish. In this short review, the author has attempted to propose a novel approach for identification of new hormones that are important for SW adaptation using comparative genomic and functional studies. The author has also suggested potential hormone families that are diversified in teleost fish and appear to be involved in SW adaptation through their ion-extruding actions.


Retinal detachment in pseudophakia.
In a series of cataract patients excluding myopic individuals, under age 60 years, and cases in which vitreous loss occurred, retinal detachment was no less frequent after intracapsular cataract extraction and Sputnik iris supported lenses than in controls. Both groups were followed up for a minimum of two years. The detachments predominantly occurred from retinal breaks in areas of the retina that looked normal preoperatively.


Isolation and characterization of a gene encoding cinnamoyl-CoA reductase from Isatis indigotica Fort.
A novel cinnamoyl-CoA reductase gene, designated as Iiccr (GenBank Accession No. GQ872418) was cloned from Isatis indigotica Fort. The full-length cDNA of Iiccr was 1368 bp with an ORF of 1026 bp that putatively encoded a polypeptide of 341 amino acids, with a predicted molecular mass of 37.50 kDa. The deduced amino acid sequence of IiCCR shared high homology with other known CCRs. No intron was detected in the genomic sequence of Iiccr. Southern-blot analysis revealed that Iiccr was a high-copy gene and real-time quantitative PCR analysis indicated that Iiccr was constitutively expressed in roots, stems and leaves of I. indigotica, with the highest expression level in roots. The results from treatment experiments using different signaling components for plant defense responses including methyl jasmonate (MeJA), gibberellins (GA(3)), abscisic acid (ABA) and ultraviolet-B revealed that expression of IiCCR had a prominent diversity. The full-length of ORF was sub-cloned into prokaryotic expression vector pET32a(+), which was then transferred into E. coli BL21(DE3). The recombinant protein had high expression level in E. coli BL21(DE3) with IPTG induction. A 2.6 kb long promoter sequence was isolated and its putative regulatory elements and potential specific transcription factor binding sites were analyzed. This study will enable us to further understand the role of IiCCR in the synthesis of phenylpropanoid compounds in I. indigotica Fort. at the molecular level.


Renal effects of hypotensive anaesthesia in combination with acute normovolaemic haemodilution with hydroxyethyl starch 130/0.4 or isotonic saline.
Hypotensive anaesthesia (HA) and acute normovolaemic haemodilution (ANH) are used separately to decrease per-operative blood loss. Reducing blood viscosity by adding ANH to HA may appear profitable in a situation with lowered perfusion pressure and concern about organ ischemia. The aim of this study was to clarify the influence of HA in combination with ANH using crystalloid or colloid as replacement fluid on renal function. Hypotensive anaesthesia was induced in 11 patients referred to major spine surgery using sevoflurane in combination with fentanyl/remifentanil. Acute normovolaemic haemodilution was carried out by drawing venous blood into standard blood bags and replacing it by isotonic saline 0.9% (Group S) or HES 130/0.4 (Group V). Renal function was evaluated before, during and up to 8 h after hypotension as the glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) by means of 51Cr-EDTA and 125I-Hippuran clearances. Lowering mean arterial blood pressure decreased GFR and ERPF in both groups. During hypotension ERPF was lower in Group S (n = 5) than Group V (n = 6). Renal function was normalized postoperatively. We found a positive but non-significant correlation between the relative GFR change and the duration of hypotension. In conclusion, our study demonstrated that renal function, assessed by GFR and ERPF, is transiently reduced during the combination of hypotensive anaesthesia and acute normovolaemic haemodilution. A colloid-based fluid regime (HES 130/0.4) used for haemodilution may preserve renal function to a greater extent than a crystalloid-based regime (0.9% saline).


Regional and zonal variations in the sulfation patterns of chondroitin sulfate in normal equine corneal stroma.
To determine regional and zonal variation in sulfation patterns of chondroitin sulfate in normal equine corneal stroma. 22 normal eyes from 11 horses. Corneas were collected within 24 hours of death from equine necropsy specimens. After papain-chondroitinase digestion of corneal tissue, disaccharides deltaDi4S and deltaDi6S were quantified by use of capillary zone electrophoresis in the superficial, middle, and deep zones of central and peripheral regions of the cornea. For the 2 regions combined, deltaDi6S/deltaDi4S values were significantly lower in the deep and middle zones, compared with that of the superficial zone. In the central region, deep and middle zones had significantly lower deltaDi6S/deltaDi4S values than the superficial zone did. In the peripheral region, the deep zone had significantly lower deltaDi6S/deltaDi4S values, compared with superficial and middle zones. In the deep zone, the peripheral region had significantly lower deltaDi6S/deltaDi4S values than the central region did. Distribution of deltaDi6S/deltaDi4S values follows a gradient across the healthy equine cornea, being smallest in the deep and middle zones of the central region and the deep zone of the peripheral region. Regional and zonal differences in the distribution of stromal deltaDi6S and deltaDi4S may influence the role of glycosaminoglycans in health, disease, and wound repair of the equine cornea.


When surgeons face intraoperative challenges: a naturalistic model of surgical decision making.
Surgery is an environment in which being an expert requires the ability to manage the unexpected. This feature has necessitated a shift in surgical decision-making research. The present study explores the processes by which surgeons assess and respond to nonroutine challenges in the operating room. We used a grounded theory methodology supported on intraoperative observations and postoperative interviews with 7 faculty surgeons from various specialties. A total of 32 cases were purposively sampled to compile a dataset of challenging situations. Thematic data analysis yielded 3 main themes that were linked in a cyclic model: assessing the situation, the reconciliation cycle, and implementing the planned course of action. These elements were connected through 2 points of transition (ie, active and confirmatory reconciliation), during which time the surgeons continue to act although they may change the course of their action. The proposed model builds on existing theories of naturalistic decision making from other high-stakes environments. This model elaborates on a theoretic language that accounts for the unique aspects of surgery, making it useful for teaching in the operating room.


Spontaneous resolution of syringomyelia in an adult patient with tight cisterna magna.
Spontaneous resolution of syringomyelia in adult patients with Chiari malformation is exceptionally rare, with only 10 cases having been reported. A 21-year-old man working as a carpenter presented with a 1-year history of paresthesias in his right arm. A magnetic resonance imaging scan disclosed a cervicothoracic syrinx associated with tight tonsillar impaction of the cisterna magna without herniation. The patient left the carpentry job and underwent close monitoring with serial clinical and neuroradiological controls. The patient's symptoms gradually disappeared and magnetic resonance imaging studies revealed progressive shrinkage of the syrinx despite persistence of crowding of posterior fossa structures at the level of the foramen magnum. This case suggests that spontaneous resolution of syringomyelia can occasionally be triggered by the cessation of daily physical strain in patients with tight cisterna magna. Health care professionals should be aware that strenuous physical activities could affect the natural history of syringomyelia.


Mapping the nanoparticle-coating monolayer with NMR pseudocontact shifts.
Lanthanide ions Yb(3+) and Tb(3+), once bound to the monolayer of organic molecules coating the surface of gold nanoparticles, induce pseudo-contact shifts on the signals of nearby nuclear spins. This not only allows the investigation of the average structure of the ligands in the monolayer but also the mapping of the position of organic molecules bound to it.


Robotic Inguinal Hernia Repair Outcomes: Operative Time and Cost Analysis.
Robotic inguinal hernia repair is the latest iteration of minimally invasive herniorrhaphy. Previous studies have shown expedited learning curves compared to traditional laparoscopy, which may be offset by higher cost and longer operative time. We sought to compare operative time and direct cost across the evolving surgical practice of 10 surgeons in our healthcare system. This is a retrospective review of all transabdominal preperitoneal robotic inguinal hernia repairs performed by 10 general surgeons from July 2015 to September 2018. Patients requiring conversion to an open procedure or undergoing simultaneous procedures were excluded. The data was divided to compare each surgeon's initial 20 cases to their subsequent cases. Direct operative cost was calculated based on the sum of supplies used intra-operatively. Multivariate analysis, using a generalized estimating equation, was adjusted for laterality and resident involvement to evaluate outcomes. Robotic inguinal hernia repairs were divided into two groups: early experience (n = 167) and late experience (n = 262). The late experience had a shorter mean operative time by 17.6 min (confidence interval: 4.06 - 31.13, p = 0.011), a lower mean direct operative cost by $538.17 (confidence interval: 307.14 - 769.20, p < 0.0001), and fewer postoperative complications (p = 0.030) on multivariate analysis. Thirty-day readmission rates were similar between both groups. Increasing surgeon experience with robotic inguinal hernia repair is associated with a predictable reduction in operative time, complication rates, and direct operative cost per case. Thirty-day readmission rates are not affected by the learning curve.


Prevalence and risk factors for High-Risk Human Papillomavirus (hrHPV) infection among HIV-infected and Uninfected Rwandan women: implications for hrHPV-based screening in Rwanda.
New World Health Organization guidelines recommend high-risk human papillomavirus (hrHPV) screen-and-treat strategies for cervical cancer prevention. We describe risk of, and risk factors for, testing hrHPV positive in a pilot study of hrHPV screen-and-treat conducted in Rwanda. A total of 2,964 women, 1,289 HIV-infected (HIV [+]) and 1,675 HIV-uninfected (HIV [-]), aged 30-60 years and living in Rwanda were enrolled in 2010. Cervical specimens were collected and tested by careHPV, a DNA test for a pool of 14 hrHPV types. Prevalence with binomial 95% confidence intervals (95% CI) and determinants of testing hrHPV positive were calculated. hrHPV prevalence was higher in HIV [+] (31.8%, 95% CI = 29.2-34.4%) than HIV [-] women (8.2%, 95% CI = 6.7-9.8%; P < 0.0001). Among HIV [+] women, there was a significant trend (ptrend <0.001) of higher hrHPV prevalence with lower CD4 cell count, with the highest hrHPV prevalence among those with <200 CD4 cell counts (45.5%, 95% CI = 34.8-56.4%). In multivariate analysis of HIV [+] women, testing hrHPV positive was positively associated CD4 count of <200 cells/μL, history of 3 or more sexual partners, and history of using hormonal contraception, and negatively associated with older age. In HIV [-] women, testing hrHPV positive was negatively associated only with older age groups of 45-49 and 50-60 years and surprisingly was not associated with lifetime number of sexual partners. hrHPV prevalence is high in HIV [+], especially in women with the lowest CD4 cell counts, which may have implications for utilizing hrHPV-based screening strategies such as screen-and-treat in these high-risk subgroups.


Lipid transfer proteins are encoded by a small multigene family in Arabidopsis thaliana.
Lipid transfer proteins (LTPs) are small, basic and abundant proteins in higher plants. They are capable of binding fatty acids and of transferring phospholipids between membranes in vitro. LTPs from this family contain a signal peptide and are secreted in the cell wall. Their biological function is presently unknown. LTPs have been suggested to participate to cutin assembly and to the defense of the plants against pathogens. A genetic approach should prove useful to provide clues on their in vivo functions. Here, the characterization of the LTP gene family in Arabidopsis thaliana is described. At least 15 genes were identified, their map position determined and the expression pattern characterized for six of them. All the sequences exhibit the typical features of plant LTPs. The molecular weight is close to 9 kDa, the isoelectric point is near 9 (except for three acidic LTPs), and typical amino acid residues such as cysteines are conserved. Genomic DNA blotting hybridization experiments performed using ltp1 to ltp6 as probes indicate that ltps form distinct 1-3 gene subfamilies which do not cross hybridize. Expression studies indicate that all the genes tested are expressed in flowers and siliques, but not in roots. Ltp1, ltp5 and ltp2 are expressed significantly in leaves, while ltp6 is detected only in 2-4-week-old leaves. In addition, ltp4 and ltp3 are strongly upregulated by abscisic acid (ABA). Tandem repeats can be noted concerning ltp1 and ltp2 on chromosome 2, ltp3 and ltp4 on chromosome 5 and ltp5 and ltp12 on chromosome 3. While ltp7, ltp8 and ltp9 map at the same position on chromosome 2, the other genes are dispersed throughout the genome. The characterization of the Arabidopsis ltp gene family will permit to initiate a genetic approach for determining the in vivo function(s) of these proteins.


Retrospective evaluation of possible renal toxicity associated with continuous infusion of vancomycin in critically ill patients.
Continuous infusion of vancomycin is increasingly preferred as an alternative to intermittent administration in critically ill patients. Intermittent vancomycin treatment is associated with an increased occurrence of nephrotoxicity. This study was designed to determine the incidence and risk factors of acute kidney injury (AKI) during continuous infusion of vancomycin. This was a retrospective, observational, two-center, cohort study in patients with microbiologically documented Gram-positive pneumonia and/or bacteremia and normal baseline renal function. Vancomycin dose was adjusted daily aiming at plateau concentrations of 15-25 μg/mL. AKI was defined as an increase in serum creatinine of 0.3 mg/dL or a 1.5 to 2 times increase from baseline on at least 2 consecutive days after the initiation of vancomycin. Primary data analysis compared patients with AKI with patients who did not develop AKI. A binary logistic regression analysis using the forward stepwise method was used to assess the risk factors associated with AKI. A total of 129 patients were studied of whom 38 (29.5%) developed AKI. Patients with AKI had higher body weight (77.3 ± 15 vs. 70.5 ± 15.2 kg; p = 0.02), more diabetes (79% vs. 54%; p = 0.01), and a higher vasopressor need (87% vs. 59%; p = 0.002). Serum vancomycin levels, body weight, and SAPS 3 score were identified as variables contributing to AKI. The incidence of AKI increased substantially when treatment duration was prolonged (14.9 ± 9.8 vs. 9.2 ± 4.9 days; p = 0.05) and plasma levels exceeded 30 μg/mL. AKI is frequently observed during continuous vancomycin infusion, particularly when conditions that cause acute (shock) or chronic (diabetes) renal dysfunction are present and vancomycin levels above target range are achieved. Although this study challenges the concept that continuous vancomycin infusion might alleviate the risk of nephrotoxicity in critically ill patients, a direct relationship between vancomycin and nephrotoxicity remains to be proven.


Is oxidative stress involved in vernal keratoconjunctivitis? Results from a pilot study in children.
Vernal keratoconjunctivitis (VKC) is a rare chronic conjunctivitis characterized by a predominantly eosinophil-mediated inflammatory disorder that could develop critical complications such as blindness. Oxidative stress plays a pivotal role in the pathogenesis of several allergic diseases. The role of oxidative stress has been hypothesized in VKC, but no study explored this issue. Furthermore, cyclosporine A (CsA) exerts an anti-inflammatory and antioxidant action on the conjunctiva. This study aimed to assess the oxidative stress in VKC patients and controls and to study the effect of CsA on oxidative stress in these subjects. Thirty-six consecutive children, including 12 VKC (nine males, 75%; mean age 10.17; SD ± 2.48) patients without treatment, 12 VKC patients treated with CsA (nine males, 75%; mean age 9.08; SD ± 2.75), and 12 controls (CT) (seven males, 58%; mean age 8.58; SD ± 1.78), were recruited. A cross-sectional study was performed to compare H2 O2 in the serum with that in the tears of these children. Compared with CT and VKC children treated with CsA, VKC untreated children had significantly higher values of hydrogen peroxide (H2 O2 ) in the serum and the tears. No significant differences were observed between CT and VKC treated with CsA. A significant correlation was found at the linear regression analysis between serum and tear H2 O2 levels. This study provides the first report attesting that patients with VKC have high oxidative stress; furthermore, it suggests that CsA could have an anti-inflammatory and antioxidant action that could be useful to prevent the poor VKC outcome.


Isolated metastasis to optic nerve from medulloblastoma.
Isolated involvement of the optic nerve with metastatic tumor is uncommon. A 19-year-old man had a midline cerebellar medulloblastoma; a gross total removal was performed. He received postoperative radiation therapy to the whole brain, posterior fossa, and craniospinal axis. A progressive optic neuropathy developed 28 months later with radiologic evidence of an enlarged optic nerve. There was no evidence of metastatic disease elsewhere. An optic nerve biopsy showed metastatic medulloblastoma. An intramedullary metastasis developed 48 months after the primary diagnosis, and the patient died 5 months later.


Long-term exposure to ambient air pollution, genetic susceptibility, and the incidence of bipolar disorder: A prospective cohort study.
There is mounting recent evidence showing that air pollution exposure may be related to the risk of mental health, yet the association between long-term exposure to air pollution and the risk of incident bipolar disorder (BD) remains unclear. Thus we aim to identify associations between air pollution and the incidence of BD in a prospective population-based cohort. In total, 482,726 participants who were free of BD from the UK Biobank were included in this prospective study. We applied time-varying Cox proportional hazards models, accounting for relevant confounders, and used annual-year moving averages of air pollution as time-varying exposures. The genetic risk for BD was categorized into three categories (low, intermediate, and high) according to the tertiles of polygenic risk score. During a median of 10.79-year follow-up, 923 incident BD events were recorded. Long-term exposures to PM2.5, PM10, NO2, and NOx were associated with increased BD risk. Estimated HRs (95% CIs) for each interquartile range increase in PM2.5, PM10, NO2, and NOx concentrations were 1.31 (1.18-1.45), 1.19 (1.09-1.31), 1.19 (1.08-1.30), and 1.16 (1.07-1.26), respectively. Associations were still observed and even stronger at pollutant concentrations lower than WHO air quality guideline. In subgroup analysis stratified by genetic risk, we observed consistent associations between all pollutants and BD risk in intermediate and high genetic risk groups, but not in low genetic risk group. For example, the HRs (95% CIs) for PM2.5 were 1.00 (0.94-1.53), 1.30 (1.06-1.59), and 1.34 (1.16-1.54) in low, intermediate, and high genetic groups, respectively. In conclusion, long-term exposure to air pollution was significantly associated with an elevated risk of BD. Associations of air pollution with BD occurred only within intermediate and high genetic risk categories and were even stronger at the pollutants levels below WHO air quality guidelines. These findings could help inform policy makers regarding ambient air quality standards and BD management.


The effects of crystal size distributions on the crystallinity analysis of bone mineral.
The mechanisms by which crystal size distributions affect the usual method of quantities X-ray diffraction analysis of bone mineral have been determined on synthetic crystals. It was observed that each component of a crystal-size distribution diffracts independently. This independence causes systematic nonlinear behavior in the plot of integrated intensity vs. broadening parameter curves. The nonlinearity resulted in an overestimation of the amount of nondiffracting material present in bone mineral. Because crystal size distributions may vary for different crystallographic directions, it is strongly suggested that the usual practice of adding the c-axis and a-axis integrated intensities to estimate the crystallinity of the sample be discontinued. Methods of understanding the crystal size distribution function in bone mineral are discussed and evaluated.


Central venous catheter thrombosis complicated by paradoxical embolism in a patient with diabetic ketoacidosis and respiratory failure.
Paradoxical embolus should be suspected in young patients with cerebrovascular events who do not have any vascular risk factors. There is significant controversy as to how best to treat his phenomenon. A case observation in a tertiary care center. A 46-year-old was admitted to the intensive care unit (ICU) for unresponsiveness secondary to diabetic ketoacidosis and acute respiratory distress syndrome. He was intubated, and central access was obtained through the right internal jugular vein. Initial computed tomography (CT) scan of his brain was unremarkable. Four days later, he suddenly became increasingly unresponsive. Repeat CT scan of the brain revealed large bilateral posterior infarcts. Transesophegeal echocardiogram revealed a patent foramen ovale (PFO), and Doppler ultrasound revealed a thrombus in the low right jugular vein. He was anticoagulated for 3 months with no intervention for his PFO. This case emphasizes the potential complications of the use of central lines in ICUs, particularly in patients with diabetic ketoacidosis in whom sluggish blood flow may predispose to a procoagulant state.


Ictal spitting: clinical and electroencephalographic features.
To identify clinical and EEG correlates of ictal spitting automatisms and to assess their reliability in indicating the hemisphere of seizure onset. The epilepsy-monitoring database (1994-2002) of the Cleveland Clinic Foundation (CCF) was searched for patients with a definite history of ictal spitting. All available documents of the patients, particularly their original video and EEG data, were reviewed. Twelve (0.3%) of the approximately 4000 patients had a documented history of ictal spitting. In seven of them, 15 seizures with spitting automatisms were recorded. All of them started with an aura or arousal out of sleep. In six of the seven patients (12 of 15 seizures), EEG onset was clearly lateralized to the right, nondominant hemisphere. Spitting occurred at a median time of 21 s after EEG seizure onset. At that time, predominantly fast, high-amplitude theta (5-7 Hz) was seen in the hemisphere of seizure onset, maximum temporal. In all but one of the total 12 patients, the epileptogenic zone was in the temporal lobe. In nine of the 12 patients, seizure onset was in the non-language-dominant hemisphere. Two patients had seizures arising from the language-dominant hemisphere; in another patient, the side of the seizure onset could not be determined. Ictal spitting is an uncommon feature of epileptic seizures. Although the symptomatogenic area is probably outside the temporal lobe, it is most frequently seen in temporal lobe epilepsy of the right, nondominant hemisphere.


Spectral bandwidths for the detection of color.
The spectral properties of human color detection mechanisms were measured using a noise masking technique that minimizes the possibility of off-axis looking and artifactually narrow estimates of bandwidth. Observers were induced to use a single detection mechanism throughout a spectral bandwidth measurement by using sectored noise to mask a time-varying signal of fixed chromatic properties. Sectored noise draws samples from sectors of variable width in the color plane, centered on the signal axis. Contrast thresholds for equiluminant signals that appeared yellow, orange, red and violet were found to depend on the power of the noise, projected along the chromatic axis of the signal, but not on the sector width of the noise. These results are consistent with the activity of spectrally broadband, linear detection mechanisms that are tuned to the signal color directions tested.


Importance of jugular valve incompetence in contrast transcranial Doppler ultrasonography for the diagnosis of patent foramen ovale.
Transcranial Doppler (TCD) ultrasound with the intravenous injection of agitated saline as contrast (cTCD) is an effective method for detecting right-to-left intracardiac and extracardiac shunt (RLS); however, the sensitivity of cTCD in the diagnosis of RLS remains slightly less than that of transesophageal echocardiography, even in patients with adequate transtemporal ultrasonic bone windows. The authors present a case with cTCD underestimating RLS because of jugular valve incompetence in a 42-year-old man presenting with an episode of transient aphasia. Three weeks after transcatheter closure of a patent foramen ovale associated with an atrial septal aneurysm, he experienced 2 episodes of amaurosis fugax. Following a negative 45-minute embolus detection study with power M-mode TCD, the patient underwent a cTCD study with monitoring of the left middle cerebral artery (MCA), the anterior cerebral artery, and the submandibular extracranial internal carotid artery. A single microbubble (MB) was detected in the left MCA in only 1 of 5 studies; the remaining runs all failed to detect an RLS. Significant MB reflux was noted in the left internal jugular vein because of jugular valve incompetence. The authors conclude that incompetence of the jugular vein valve can result in a false negative cTCD study for RLS detection.


Analysis and challenges of robust E-exams performance under COVID-19.
Nowadays under COVID 2019, e-learning has become a potential prop approach of technology in education that provides contemporary learners with authentic knowledge acquisitions. As a practical contribution, electronic examination (e-exam) is a novel approach in e-learning designed to solve traditional examination issues. It is a combination of assorted questions designed by specialized software to detect an individual's performance. Despite intensive research in this area, the performance of e-exams faces challenges such as authentication of the examinee's identity and answered papers. This paper aims to present the experiences of educational organizations in e-exam and e-evaluation as an essential tool of e-learning in various countries. The paper recommends that under the global pandemic COVID 2019 evaluating students using intensive continuous evaluation, including e-exam supported by authentication methods, which may help detect and reduce or even prevent student violations. The results show that the most used LMS tools were the Moodle and proprietary solutions which were 75% both among many other LMS tools i.e., Blackboard and eFront. The least develop countries are prefer to use open source and proprietary due to the zero cost of these solutions. The internet speed, cost and authenticity were the most challenges faced e-exams centers, which were 99%, 82%, and 68%, respectively.


Lessons from crystals grown in the Advanced Protein Crystallisation Facility for conventional crystallisation applied to structural biology.
The crystallographic quality of protein crystals that were grown in microgravity has been compared to that of crystals that were grown in parallel on earth gravity under otherwise identical conditions. A goal of this comparison was to assess if a more accurate 3D-structure can be derived from crystallographic analysis of the former crystals. Therefore, the properties of crystals prepared with the Advanced Protein Crystallisation Facility (APCF) on earth and in orbit during the last decade were evaluated. A statistical analysis reveals that about half of the crystals produced under microgravity had a superior X-ray diffraction limit with respect of terrestrial controls. Eleven protein structures could be determined at previously unachieved resolutions using crystals obtained in the APCF. Microgravity induced features of the most relevant structures are reported. A second goal of this study was to identify the cause of the crystal quality enhancement useful for structure determination. No correlations between the effect of microgravity and other system-dependent parameters, such as isoelectric point or crystal solvent content, were found except the reduced convection during the crystallisation process. Thus, crystal growth under diffusive regime appears to be the key parameter explaining the beneficial effect of microgravity on crystal quality. The mimicry of these effects on earth in gels or in capillary tubes is discussed and the practical consequences for structural biology highlighted.


[Does weather modify headaches? An empirical evaluation of bio-weather categorization].
Headache patients frequently refer to the weather as a triggering factor for their headaches. Apart from a literature review, we tested empirically the generally used classification of weather epochs into a so called bio-weather categorization. Headache diary data (frequency, duration, intensity) of 98 patients in a headache trial were correlated with the concurrent bio-weather classification. Correlations were small and significant only for the summer-half of the year (contingency coefficients between 0.04 and 0.06). The classification of certain types of weather as headache prone as used in the current bio-weather classification could only partly be verified. There is a clear but small correlation between headache and weather. More, and more fine-grained, studies are warranted, especially for identifying those patients at risk for weather prone headaches. Clinically more important is the weather as a source of causal attributions.


Environment associated with morphine and experience of aggression modulate behaviors of postdependent mice.
Contexts associated with drug use can acquire secondary reinforcing properties. Furthermore, context-specific withdrawal has been observed to reflect a relatively long-lasting learned response. The aim of this study was to evaluate the effect of the environment paired with morphine after 15 days of abstinence. In the first experiment, isolated male mice received saline or morphine either in their home cage or in the distinctive environment, performing two agonistic encounters in the distinctive environment during spontaneous withdrawal. Similar groups were assigned but without aggression encounters during withdrawal. In the second experiment, animals received saline or morphine as previously described but suffered two naloxone-induced withdrawals during agonistic encounters. In all cases, after the second withdrawal, animals were drug-free during 15 days and then an aggression test took place in the distinctive environment. Results show that experience of aggression during this spontaneous withdrawal causes an increase in the level of aggression exhibited when animals are drug free, in comparison with others in which this experience does not exist. Environment associated with morphine administration decreases conditioned physical signs of withdrawal and to a smaller extent aggression. It could be suggested that environment associated with morphine administration decreases the abnormal behaviors exhibited in postdependent mice.