Chemiluminescence as a diagnostic aid in the detection of oral cancer and potentially malignant epithelial lesions.
Chemiluminescence was evaluated as a diagnostic aid in the detection of oral cancer and potentially malignant epithelial lesions (PMELs) by comparing it against 1% tolonium chloride mouth rinse. Forty-six clinically identified lesions [14 primary squamous cell carcinoma (SCC), 26 PMELs and 6 benign lesions] and five cases of normal oral mucosa from 40 subjects (inclusive of 10 previously treated SCC cases) were examined with a commercial chemiluminescent kit (Vizilite) and tolonium chloride. Biopsy and histological verification of 31 lesions disclosed 14 SCC (45.2%), 10 epithelial dysplasias (32.3%), 5 lichen planus (16.1%) and 2 benign lesions (6.4%). For the remaining 15 lesions, a biopsy was not performed owing to patient's lack of consent or ill-health. The five cases of normal oral mucosa which tested negative for both tools were also not biopsied for ethical reasons. Sensitivity for Vizilite and tolonium chloride was 100% and 70.3%, respectively; and specificity was 14.2% for Vizilite and 25% for tolonium chloride. Their accuracy was 80.6% and 64.5%, respectively. Current findings suggest that chemiluminescence is a more reliable diagnostic tool than tolonium chloride in the detection of oral cancer and PMELs, and for follow-up of patients treated for the same.


Is the insect or the plant the driving force in the cinnabar moth - Tansy ragwort system?
The interactions between cinnabar moth, Tyria jacobaeae L. and its food plant, tansy ragwort, Senecio jacobaea L. were studied for 4 to 6 years at 9 sites in North America to assess if the herbivore drove the dynamics of the plants or if the plants determined the dynamics of the insects. Cinnabar moth larval density is not closely related to changes in the size and spacing of tansy ragwort plants although high densities of larvae were associated with a high proportion of rosettes the next year. Fluctuating moth populations live in areas where rosettes are small, closely spaced and numerous compared to flowering stem plants. This situation is also associated with greater larval dispersal which may lead to over exploitation of the food supply. The coefficient of variation of both the size of rosettes and the distance between clumps of plants is associated with the coefficient of variation in moth density. This suggests that the plants may be driving the dynamics of the insect populations. The size of the moth egg batches is correlated to the size of the flowering stem plants in the previous year, indicating an adjustment between moth fecundity and food plant size. The conclusion is that environmental factors such as weather and soil type determine to a large degree the characteristics and variation in the plant populations and this in turn controls the dynamics of the insects. The relation of this situation to the biological control of weeds is discussed.


Avian pox virus. An ultrastructural study on a cherrug falcon. Brief report.
The ultrastructure and maturation of avian pox particles is described in the rare case of a naturally infected hawk (Falco cherrug). As in other cells infected by fowlpox virus two types of inclusion bodies are encountered in the cytoplasm: firstly assemblies of fluffy filamentous material apparently giving rise to immature virions. They are thought to present virus factories (inclusion body B). Secondly mature virus particles budded into extensive groupings (Bollinger bodies, inclusion body A) which display a fine structure identical to other strains of fowlpox virus.


Various polystyrene topologies built from tailored cyclic polystyrene via CuAAC reactions.
Rapid CuAAC cross-coupling reactions catalyzed by CuBr/PMDETA in toluene afforded complex architectures from functional polymeric cyclic blocks. Various topologies (from paddle-like to 3-arm stars) rapidly formed with high conversion at 25 °C. Remarkably, this approach overcame significant steric hindrance linking polymeric cyclic structures with high coupling efficiency.


Temporal and spatial organization of tyrosine hydroxylase-immunoreactive cell groups in the embryonic brain of an elasmobranch, the lesser-spotted dogfish Scyliorhinus canicula.
We have studied the development of catecholaminergic (CA) neuronal groups in the brain of the dogfish Scyliorhinus canicula using immunohistochemistry to tyrosine hydroxylase (TH). The earliest TH-immunoreactive (THir) cells were detected in the primordia of the posterior tubercle and suprachiasmatic nuclei (PTN and SCN, respectively) of stage 26 embryos. At stage 28, THir cells were also seen extending between the SCN and the PTN at ventral thalamic levels. At stage 30, some THir cerebrospinal fluid-contacting neurons and migrated THir cells were found in the walls of the posterior recess, and a few weakly THir cells also appeared at the isthmus level (locus coeruleus) and in the caudal rhombencephalic tegmentum. At stage 31, further THir cell groups appeared in the synencephalon and midbrain (ventral tegmental area/substantia nigra, VTA/SN), and the rhombencephalon (viscerosensory and visceromotor columns). At stage 32, the first THir cells appeared in the pallium, the olfactory bulb and the preoptic area. THir cells are seen in the retina from stage 33. The developmental sequence of THir cell groups in dogfish appears to be rather similar to that described for teleosts, apart from the appearance of the VTA/SN and pallial cells, which lack in teleosts.


Sternoclavicular joint surgery: how far does danger lurk below?
Surgical stabilization of the sternoclavicular joint (SCJ) is infrequent, and cardiothoracic surgery assistance is often recommended. Patient safety and surgeon efficiency may be improved by greater understanding of the anatomic relationships near the SCJ. The purpose of this study is to determine the distances from the SCJ to critical structures in the superior mediastinum. Distances from the posterior SCJ to adjacent mediastinal structures were recorded using contrast computed tomography scans of 49 consecutive patients. Patient sex, height, body mass index, side, age, and thickness of the sternum and medial clavicle were also recorded. The mean distance to the nearest anatomic structure deep to the clavicular region of the SCJ was 6.6 mm and was 12.5 mm for the sternal region. The clavicle was an average thickness of 18 mm, and the sternum was an average thickness of 17 mm. The closest structure was the brachiocephalic vein. An artery was identified as the closest structure in 21.2% of patients. Distance differences between the right and left sides were noted, but sex had no bearing on distance to structures. Multiple mediastinal structures are close to the SCJ. The most frequent structure at risk of injury deep to the SCJ is the brachiocephalic vein. Such knowledge may improve patient safety.


Influence of precipitated calcium carbonate (CaCO3) on shiitake (Lentinula edodes) yield and mushroom size.
Synthetic substrate consisting of oak sawdust (50%), white millet (28%), winter rye (11%) and soft red wheat bran (11%) was non-supplemented or supplemented with 0.2%, 0.4% or 0.6% (dry weight basis) precipitated calcium carbonate (CaCO(3)). Shiitake (Lentinula edodes) was grown in two crops to determine the effect of three CaCO(3) levels on mushroom yield and size. Yields and biological efficiencies (averages for two crops) from substrates non-supplemented with CaCO(3) were lower by 14.1%, 18.4% and 24.9% compared to treatments supplemented with 0.2%, 0.4% and 0.6% CaCO(3), respectively. Mushroom size (weight) was larger with non-supplemented substrate (16.8 g) compared to substrate supplemented with 0.6% CaCO(3) (15.1 g). However, mushroom production was more consistent from crop to crop when 0.6% CaCO(3) was added to substrate.


Development and Preliminary Validation of the PrEP Empowerment Scale.
Informed by the Health Care Empowerment Model, a measure of PrEP Empowerment was developed and assessed for preliminary reliability and validity. Participants (N = 100) were invited to complete a survey during regular clinic visits. A subset (n = 84) volunteered to provide blood samples to assess plasma tenofovir (TFV) levels for recent PrEP adherence. A five-factor measure explained 70% of the total variance. Associations with internalized PrEP stigma, PrEP adherence self-efficacy, and plasma TFV were assessed. Results supported the multidimensional nature of PrEP Empowerment and reliability and validity. Additional research is needed in populations with varying PrEP experience and greater gender and ethnic representation.


Improving the uptake of medical device training to promote patient safety.
Safe and effective patient care is dependent on the appropriate use of medical devices, so it is necessary to ensure that all nursing staff are competent in their use. This article describes how one urology ward in a large acute NHS trust has supported medical device training for its staff. To explore the potential benefits of introducing a ward time out training day to improve staff competency in the use of medical devices. A training programme was introduced for the urology ward staff, which involved ward time out training days that covered medical device and mandatory training, alongside evidence to support nurses' revalidation and a forum for peer support. Since the ward time out training days were introduced in 2015, medical device training competency among the urology ward staff has risen from 65% to 97% across all staff groups, including nurses and healthcare assistants. The ward time out training days were beneficial for the urology ward staff, and increased their medical device training competency. Additional benefits of the ward time out training days included team integration, improved knowledge and competency among staff, and nurses undertaking continuing professional development hours that contributed towards their revalidation.


Determination of pesticides in river water using rotating disk sorptive extraction and gas chromatography-mass spectrometry.
The rotating disk sorptive extraction (RDSE) technique was applied to the determination of pesticides in aqueous samples. Pesticides of different polarities were considered in this study: chlorpyrifos, diazinon, fenvalarate, cyhalothrin, cypermethrin, lindane and malathion. The sorptive/desorptive behavior of the pesticides was studied using a rotating disk containing a polydimethylsiloxane (PDMS) phase on one of its surfaces. The analyte polarity was a significant factor in the extraction time; shorter extraction times were required for the more apolar pesticides. The optimum variables for the extraction of all analytes were: extraction time of 3h, sample volume of 25 mL, rotational velocity of the disk 1250 rpm, desorption time of 30 min using methanol. For pesticides with values of Log K(ow)>4, the extraction time can be reduced to 30 min for a quantitative extraction. Under these conditions, recoveries between 76% and 101% were obtained for the target pesticides, and the repeatability of the methodology, expressed as relative standard deviation, was determined to be between 10% and 20%. Additionally, the limits of detection of the analytes were lower than 3.1 μg L(-1). The extraction method developed using the RDSE was compared to a stir bar sorptive extraction (SBSE) under the same conditions. It can be observed that the extraction using the rotating disk offers higher recoveries because of its higher PDMS volume and its higher surface area to volume ratio that allows for improved mass transfer.


Sensitive visualization of antigen-antibody reactions in dot and blot immune overlay assays with immunogold and immunogold/silver staining.
The use of colloidal gold and colloidal gold followed by silver enhancement as marker for dot or blot immune overlays is described. Colloidal gold probes concentrating at the sites of immune reaction gradually develop a pinkish colour during incubation that can be seen with the naked eye. With a physical developer, very high sensitivity and contrast is obtained by silver precipitation on the gold marker. Comparison of the immunogold and immunogold/silver staining methods with the indirect, PAP and ABC immunoperoxidase methods demonstrates that colloidal gold probes are excellent markers for immune overlay assays.


Application of the laser to the study of pathogenic fungi.
Laser microanalysis has been applied to the study of pathogenic fungi. Such a method allows chemical information to be obtained and permits the detection of 74 elements in the periodic system of Mendeleev from lithium (3) to uranium (92).


Promoting health, promoting women: the construction of female and professional identities in the discourse of community health workers.
Community health worker (CHW) programs are implemented in the third world and among racial minorities in the U.S. by public health professionals with the goal of improving people's access to basic health services. There is a shared view that women's roles as mothers make them effective CHWs because most health practices are located within the realm of the family. The objective of this paper is to inquire how and what concepts of woman are constructed and promoted in CHW programs. Viewing CHW as a discourse, I examine literature on CHWs using a critical feminist perspective and insights from narrative and rhetorical analyses. I argue that CHW positions women living in the third world and non-white Hispanic women in the U.S. as the "other" woman. The natural attributes of this other woman include mother, care giver, oppressed, child-like, and victim of patriarchy, religion, poverty, and diseases. These attributes are used to define categories of the female such as "the third world woman" and "Hispanic woman". These categories, in turn, define two unnamed opposite categories: "the first world woman" and "the public health professional". I conclude that CHW is a colonizing discourse and that public health professionals and feminists need to practice reflexivity.


Short-term insomnia disorder in health care workers in an academic medical center before and during COVID-19: rates and predictive factors.
This study investigated risk factors and estimated rates of acute insomnia disorder in health care workers at the onset of the coronavirus disease 2019 (COVID-19) pandemic. A Qualtrics survey of more than 2,300 health care providers was conducted in a single academic health system on May 15, 2020, including practicing attending physicians, residents and fellows in training, advanced practice providers, and nurses. Six hundred and sixty-eight responded (29% response rate). The survey employed the Research Diagnostic Criteria for insomnia disorder to diagnose acute insomnia disorder. Five hundred seventy-three respondents had no missing data pertaining to sleep, with a mean age of 43.4 ± 12.5 years and 72% women. The rate of insomnia disorder before COVID-19 was 44.5%, while after COVID-19 it was 64.0%. Of persons with insomnia disorder before COVID-19 10.2% stated it had resolved during COVID-19, while 43.4% of persons who did not have insomnia disorder before COVID-19 developed acute insomnia disorder during COVID-19 (χ² = 145.2; df = 1; P < .0001). New cases of acute insomnia disorder were related positively to female sex, advancing age, and less time spent in direct patient care. Acute insomnia disorder was exceptionally common in this sample of tertiary care health care workers. The effects of sex and age were similar to what has been generally described as risk factors for insomnia. The surprising finding that less time spent in direct patient care was associated with more cases of acute insomnia disorder might be explained by the poorly understood stresses of working from home during COVID-19.


What it's really like: the complex role of medical students in end-of-life care.
Medical student end-of-life care training provides insight into the hidden curriculum and physician professional development. Second-year medical students at a university medical center listen to a panel discussion of 4th-year students and residents describing their end-of-life care experiences during clerkships. This discussion is intended to provide "anticipatory guidance" to 2nd-year students about challenging situations they might encounter on the wards. The purpose of this study was to analyze the content of the panel discussions by 4th-year students and residents to better understand their views of the end-of-life care curriculum. We performed a qualitative content analysis of transcripts from 2 years of panel discussions. Participants' comments focused primarily on the complexity of the role of medical students in end-of-life care. Three major themes emerged in the sessions: defining professional identity, conflicting expectations, and limited medical experience. The role of medical students in end-of-life care can be complex, confusing, and contradictory. Emotional support and elucidating the hidden curriculum may assist students with the process of physician enculturation and end-of-life care education.


Correction: Analysis of Secure Apps for Daily Clinical Use by German Orthopedic Surgeons: Searching for the "Needle in a Haystack".
[This corrects the article DOI: 10.2196/17085.].


Caffeic acid attenuates oxidative stress, learning and memory deficit in intra-cerebroventricular streptozotocin induced experimental dementia in rats.
Oxidative stress has been implicated in cognitive decline as seen during normal aging and in sporadic Alzheimer's disease (AD). Caffeic acid, a polyphenolic compound, has been reported to possess potent antioxidant and neuroprotective properties. The role of caffeic acid in experimental dementia is not fully understood. Thus the present study was designed to investigate the therapeutic potential of caffeic acid in streptozotocin (STZ)-induced experimental dementia of Alzheimer's type in rats. Streptozotocin (STZ) was administered intracerebroventrically (ICV) on day 1 and 3 (3mg/kg, ICV bilaterally) in Wistar rats. Caffeic acid was administered (10, 20 and 40mg/kg/day p.o.) 1h following STZ infusion upto 21st day. Morris water maze and object recognition task were used to assess learning and memory in rats. Terminally, acetylcholinesterase (AChE) activity and the levels of oxido-nitrosative stress markers were determined in cortical and hippocampal brain regions of rats. STZ produced significant (p<0.001) learning and memory impairment, oxido-nitrosative stress and cholinergic deficit in rats. Whereas, caffeic acid treatment significantly (p<0.001) and dose dependently attenuated STZ induced behavioral and biochemical abnormalities in rats. The observed cognitive improvement following caffeic acid in STZ treated rats may be due to its antioxidant activity and restoration of cholinergic functions. Our results suggest the therapeutic potential of caffeic acid in cognitive disorders such as AD.


Flow-through cytometry of meningiomas and cultured meningioma cells.
Flow cytometric techniques were used to compare the DNA content, size and viability of meningioma cells obtained directly from surgical specimens with the same cells after a period of culture. Cells isolated from the original meningiomas and cells in primary culture was similar with regard to size and DNA content, regardless of the histologic subclassification of tumor. The cell populations were essentially diploid with a small proportion of tetraploid cells. Viable cells were smaller and more uniform in size than the nonviable cells. An increase in the number of cells having an elevated DNA content was seen with cultures repeatedly transferred. The latter results suggest that any transfer of information from long-term cultured meningioma cells to the in vivo situation must be done with caution.


An essential role of Tap42-associated PP2A and 2A-like phosphatases in Ty1 transcriptional silencing of S. cerevisiae.
We previously reported that overproduction of non-translatable mRNA silences Ty1 transcription, possibly via functional inactivation of the nuclear cap-binding complex (CBC) and subsequent hyperstimulation of the TORC1 pathway. Further experimental evidence for CBC-to-TORC1 signalling in Ty1 transcriptional silencing is presented here. The role of Tap42 (a key downstream component of the TORC1 pathway) was tested. Mutations affecting components of the Tap42-associated PP2A/2A-like phosphatases (Tap42, redundant Pph21/Pph22 and Sit4) eliminate Ty1 transcriptional silencing and epistasis experiments show that the phosphatases function downstream of CBC. Thus, Tap42 functions in the same positive direction as Sit4, Pph21 and Pph22 in Ty1 transcriptional silencing, providing support to the idea that Tap42 may play a positive role in phosphatase activity in response to TORC1 signalling. Moreover, the pph21-102 and sit4-102 mutations affecting interactions of the phosphatases with the Tap42 regulator also abolish Ty1 transcriptional silencing, confirming that the Tap42-phosphatase complex is one required for TORC1-mediated Ty1 transcriptional silencing. PP2A holoenzyme activity, which is independent of Tap42 and TORC1, is not essential for Ty1 transcriptional silencing, strengthening the argument that TORC1-specific signalling underlies Ty1 transcriptional silencing.


Minimum 5-year follow-up results and functional outcome of rotating-platform high-flexion total knee arthroplasty: A prospective study of 701 knees.
To evaluate the midterm clinical outcome, functional outcome, associated complications, and survivorship of high-flexion posterior-stabilized rotating-platform total knee arthroplasty. We prospectively analyzed 701 knees in 501 patients, who underwent total knee arthroplasty using high-flexion posterior-stabilized rotating-platform prosthesis. Patients were assessed preoperatively and postoperatively for their ability to kneel, do full squats, do half squats, and sit cross-legged by using a patient-administered questionnaire. Significant improvement was seen in patient-reported outcomes at the mean follow-up of 5.5 (range, 5-7) years. Mean flexion achieved postoperatively was 135° (range, 120°-150°) from a mean preoperative flexion of 108.8° (range, 90°-120°). Ninety-five percent of patients were able to sit cross-legged, 90% were able to kneel, 70% were able to perform a half squat, and 20% were able to perform a full squat. Posterior-stabilized, rotating-platform, high-flexion design provides good postoperative flexion, functional outcome, and good midterm survivorship.


Mental Health Issues and Special Care Patients.
Mental illness is a major health issue in the world today, yet often remains misunderstood, unrecognized, and undertreated. Patients suffering from severe psychiatric disorders generally display poor oral health, often as a consequence of both lifestyle and avoidant-type behaviors that become exacerbated by their illness. Individuals with severe mental illness display a greater incidence of oral disease compared with a similar demographic not dealing with these particular disorders. Efforts to enhance the oral health of these vulnerable patients will play a significant role in the overall rebuilding of their self-esteem and contribute positively to their journey toward stability and recovery.


Cloning and nucleotide sequencing of the genes for ribosomal proteins S9 (rpsI) and L13 (rplM) of Escherichia coli.
The genes for the ribosomal proteins S9 (rpsI) and L13 (rplM) of Escherichia coli have been cloned into a lambda phage vector termed L47.1. The two genes were identified by infecting UV-light irradiated cells with the resultant phages and analyzing the protein products by two-dimensional gel electrophoresis. Suitable DNA fragments of the isolate were cloned subsequently into M13 phage vectors and their nucleotide sequence was determined by the dideoxy method. It is evident that the two genes form a transcriptional unit, the rplM gene being promoter-proximal. There is a typical signal sequence for transcriptional termination after the rpsI gene. The codon usage pattern in the two genes is similar to other ribosomal protein genes of E. coli.


Could 18F-FDG-PET/CT avoid unnecessary thyroidectomies in patients with cytological diagnosis of follicular neoplasm?
Preoperative diagnosis of thyroid nodules with "follicular neoplasm" (FN) based on fine-needle aspiration cytology (FNAC) forces thyroidectomy to exclude malignancy. This study explores if (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) provides information enough to prevent unnecessary thyroidectomies in this clinical setting. This is a prospective study involving 46 consecutive patients scheduled for thyroidectomy due to follicular neoplasm diagnosis in FNAC (36 follicular, 10 Hürthle cell neoplasms, Bethesda classification) since January 2009 until April 2012. All patients underwent preoperative (18)F-FDG-PET/CT. Abnormal (18)F-FDG thyroid uptake was assessed visually and by measuring the maximum standard uptake value (SUV max). Results were compared with definitive pathology reports. Thirteen out of 46 patients (28.3 %) were finally diagnosed with thyroid cancer. Focal uptake correlated with a greater risk of malignancy (p = 0.009). (18)F-FDG-PET/CT focal uptake showed sensitivity, specificity, positive and negative predictive values and overall accuracy of 92.3, 48.5, 41.4, 94.1 and 60.9 %, respectively. The optimal threshold SUV max to discriminate malignancy was 4.2 with an area under receiver-operating characteristic curve of 0.76 (95 % confidence interval, 0.60-0.90). Use of (18)F-FDG-PET/CT could reduce by 13-25 % the number of thyroidectomies performed for definitive benign nodules. However, it has demonstrated worse predictive ability in the subgroup of patients with diffuse uptake, oncocytic pattern in FNAC and lesions smaller than 2. (18)F-FDG-PET/CT can play a role in the management of thyroid nodules larger than 2 cm cytologically reported as follicular neoplasm without oncocytic differentiation, allowing the avoidance of a significant number of thyroidectomies for definitive benign lesions.


Introduction to hospital information systems.
The phrase, 'hospital information system', is frequently used in discussions about the flow of information throughout a hospital with the assumption that everybody has the same concept in mind. Closer examination shows that this is not necessarily the case. The author draws on his experience as the Chief Information Officer at University Hospital at Stony Brook to define a hospital information system in terms of the implementation at Stony Brook. The University Hospital Information System at University Hospital (UHIS), has received international acclaim and was recently selected by the IBM Quarterly of Australia as the world leader in hospital information systems. This paper answers four questions: What is a hospital information system? How does a hospital information system work? How do you implement a hospital information system? After the system is operational, where do you go, e.g., critical care data management, physician's office management? University Hospital at Stony Brook is located on eastern Long Island and is the tertiary care referral hospital for approximately 1.4 million people. Nothing in the hospital happens without computers. Doctors, nurses, administrators and staff at all levels rely on the system daily. The system operates 24 hours per day, seven days per week. Access to the system is through 300 terminals and 128 printers throughout the hospital. In addition to the UHIS terminals, the critical care management system which is called Patient Data Management System, (PDMS), is available at over 90 ICU beds and in the operating rooms.


Silent and humming nasal NO measurements in adults aged 18-70 years.
The concentration of nitric oxide (NO) measured from the nose is much higher than in the lower airways and increases during humming. We assessed nasal NO (nNO) normal values during breath hold and during humming in healthy adults. Nasal NO concentrations were measured in healthy adults (ages 18-70). They held their breath for 10 s and thereafter hummed as loud as possible with their mouths closed also for 10 s. During breath hold, air was passively extracted from one nostril with 700 mL min(-1). The average NO concentration at the plateau after 7-10 s was recorded and the mean of three consecutive measurements was calculated. During humming, air was extracted with 1200 mL min(-1), the peak NO values were recorded. One hundred healthy adults participated (37 men). The nNO concentrations during breath hold were distributed normally (mean: 455 parts per billion (p.p.b.), SD 147). A random subgroup of 40 out of the 100 subjects (15 men) performed nNO measurement during humming. The median peak NO value was 1019 p.p.b. (SD 561) at the first, and 837 p.p.b. (SD 408) at the second measurement. There was a significant difference between the peak NO values of first and second humming. We present normal values for nNO in adults, which can be used to assess the value of nNO in respiratory illnesses. The peak nNO values during humming are variable, and their clinical relevance remains to be shown.


Phase 3 trial of sequential versus combination treatment in colorectal cancer: The C-cubed study.
An optimal treatment strategy using oxaliplatin and bevacizumab for metastatic colorectal cancer has not been defined. We investigated whether the sequential treatment using fluoropyrimidines with bevacizumab followed by the addition of oxaliplatin at first progression was better than a combination treatment using fluoropyrimidines and oxaliplatin with bevacizumab. In the sequential treatment, the escalation from fluoropyrimidines plus bevacizumab to fluoropyrimidines plus oxaliplatin with bevacizumab was recommended in case of progressive disease. Time to failure of strategy was the primary end-point, whereas the secondary end-points were overall survival, progression-free survival, overall response rate and safety. Three hundred patients with previously untreated metastatic colorectal cancer were randomised to receive either the sequential treatment (n = 151) or the combination treatment (n = 149). The sequential treatment was superior to the combination treatment about time to failure of strategy (15.2 months; 95% CI, 12.5-17.2 months vs. 7.8 months: 95% CI, 6.3-9.5 months; P < 0.001). However, the median overall survival was 27.5 (95% CI, 24.4 to 32.7) months in the sequential treatment and 27.0 (95% CI, 22.8 to 36.0) months in the combination treatment (hazard ratio, 0.92; 95% CI, 0.66 to 1.28; P = 0.61). The overall response rate was 33.1% in the sequential treatment arm and 51.7% in the combination treatment. The findings support the extension of the sequential treatment starting from fluoropyrimidine plus bevacizumab to selected patients who do not need an objective response to the threatening disease.


Plasma levels of retinol and retinol-binding protein in patients with squamous cell carcinomas of the head and neck region.
The levels of retinol, retinol-binding protein (RBP), and prealbumin (PALB) in 53 patients with head and neck squamous cell carcinomas of various size and metastatic nature were significantly lower than in tumor-free individuals and patients suffering from premalignant lesions of the laryngeal mucosa. The levels in tumor patients remained low after tumor resection and postradiation. With regard to the possible antineoplastic role of vitamin A, the reduced plasma retinol levels are considered as a possible supporting factor in tumor development and growth. The cause of the disorder however remains unclear.


Duloxetine for the treatment of stress urinary incontinence in women: an integrated analysis of safety.
The objective was to characterize the safety of duloxetine for treatment of stress urinary incontinence (SUI) in women, using an integrated database generated from four published placebo-controlled clinical trials. The database included 1913 women randomized to duloxetine (N=958) or placebo (N=955), examining adverse events (AEs), serious adverse events (SAEs), vital signs, electrocardiograms, and laboratory analytes. AEs occurring initially or worsening during the double-blind treatment period were considered treatment-emergent (TEAE). Differences between duloxetine-treated and placebo-treated groups were compared statistically. Common TEAEs included: nausea (23.2%), dry mouth (13.4%), fatigue (12.7%), insomnia (12.6%), constipation (11.0%), headache (9.7%), dizziness (9.5%), somnolence (6.8%), and diarrhea (5.1%). Most TEAEs that emerged early were mild to moderate, rarely worsened, and resolved quickly. Overall AE discontinuation rates were 20.5% for duloxetine and 3.9% for placebo (P<.001). Most discontinuations (83%) occurred within the first month of treatment. SAEs were uncommon and did not differ between treatments. Statistically significant, but clinically unimportant mean increases in heart rate (2.4 bpm) and systolic and diastolic blood pressure (<or=2 mmHg) occurred. No arrhythmogenic potential was observed and any rare, transient, asymptomatic increases in hepatocellular enzymes normalized. Duloxetine was safe and tolerable, although transient AEs were not uncommon.


Altered expression and activation of mitogen-activated protein kinases in diabetic heart during cardioplegic arrest and cardiopulmonary bypass.
We investigated whether mitogen-activated protein kinases (MAPKs) are changed in the hearts of patients with diabetes after cardioplegia and cardiopulmonary bypass (CP/CPB) operations. Biopsies from the right atrial appendage were harvested pre- and post-CP/CPB from nondiabetic (ND) patients (n = 8, hemoglobin A1c (HbA1c) = 5.4 ± 0.12); patients with controlled diabetes (CDM) (n = 8, HbA1c = 6.5 ± 0.15); and patients with uncontrolled diabetes (UDM) (n = 8, HbA1c = 9.6 ± 0.3) undergoing coronary artery bypass grafting. The expression and/or activation of the p38-MAPK, ERK1/2, JNK, and MKP-1 in the right-atrial tissues were analyzed by Western blotting. The vasomotor function of coronary arterioles was measured by videomicroscopy. The post-CP/CPB levels of total p38-MAPK were decreased in the 3 groups as compared with their pre-CP/CPB levels (P < .05). There were increases in phospho-p38-MAPK, phospho-ERK1/2, and MKP-1 in UDM patients as compared with ND and CDM patients at baseline (P < .05). Compared to pre-CP/CPB, the post-CP/CPB levels of phospho-p38-MAPK decreased in the UDM group but were unaltered in the ND and CDM groups; however, the post-CP/CPB levels of phospho-p38-MAPK still remained greater than the post-CP/CPB levels of the other 2 groups. Post-CP/CPB levels of phospho-ERK1/2 were increased in the ND and CDM groups but were decreased in the UDM group compared to their pre-CP/CPB levels, respectively (P < .05). There were no significant differences in phospho-JNK in 3 groups at baseline. Post-CP/CPB levels of phospho-JNK, however, were increased in the 3 groups and were more pronounced in the myocardium of the UDM group (P < .05). After CP/CPB, the protein levels of MKP-1 were unchanged in the 3 groups when compared with their pre-CP/CPB levels. Post-CP/CPB levels of MKP-1, however, remained greater in the UDM group than in the ND and CDM groups. The post-CP/CPB contractile responses to the thromboxane A2 analog U46619 were significantly impaired in all 3 groups compared with pre-CP/CPB contractile responses. These impairments were more pronounced in the UDM group. Uncontrolled diabetes is associated with changes in expression of and activation of MAPKs and vasomotor dysfunction in the setting of CP/CPB.


Corrigendum to: The Impact of Concomitant Empiric Cefepime on Patient Outcomes of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections Treated With Vancomycin.
[This corrects the article DOI: 10.1093/ofid/ofz079.].


Molecular cloning of an arabidopsis homologue of GCN2, a protein kinase involved in co-ordinated response to amino acid starvation.
DNA homologous to the yeast ( Saccharomyces cerevisiae) protein kinase gene, GCN2, was amplified from arabidopsis [ Arabidopsis thaliana (L.) Heynh.] RNA and given the name AtGCN2. The AtGCN2 peptide sequence included adjacent protein kinase and histidyl tRNA synthetase-like domains and showed 45% sequence identity with the GCN2 peptide sequence in the protein kinase domain. AtGCN2 transcripts were detectable in RNA from roots, leaves, stems, buds, flowers, siliques and seedlings. GCN2 is required for yeast cells to respond to amino acid starvation. Expression of AtGCN2 in yeast gcn2 mutants complemented the mutation, enabling growth in the presence of sulfometuron methyl, an inhibitor of branched-chain amino acid biosynthesis, and 3-aminotriazole, an inhibitor of histidine biosynthesis.


Efficacy of transcatheter arterial chemoembolization followed by sorafenib for intermediate/advanced hepatocellular carcinoma in patients in Japan: a retrospective analysis.
Sorafenib might prevent hepatocellular carcinoma (HCC) recurrence caused by the promotion of neoangiogenesis after transarterial chemoembolization (TACE). To evaluate the efficacy and safety of TACE followed by sorafenib for treating advanced HCC. We retrospectively analyzed 95 advanced HCC patients treated with TACE between July 2008 and December 2012 at our institution. Twenty-four patients received TACE followed by sorafenib within 14 days (S-TACE) and 71 received TACE alone. Progression-free survival (PFS) and cumulative survival from the time of non-responsiveness to TACE were compared between groups and predictive factors for PFS were analyzed. The median patient age was 72.2 years and 74 patients were male (77.9 %). Although median tumor size was similar between groups, the mean tumor number was significantly higher in the S-TACE versus TACE-alone group (16 vs. 8, P = 0.04). The number of prior treatments was significantly higher in the S-TACE group. Other baseline variables were similar. There were two severe adverse events in the S-TACE group and none in the TACE-alone group. Median PFS (189 vs. 106 days, P = 0.02) and median overall survival time (861 vs. 467 days, P = 0.01) from the time of non-responsiveness to TACE were significantly longer with S-TACE than TACE alone. Adjusting for significant factors in univariate analysis, multivariate analysis indicated that sorafenib administration, tumor size, and alanine transaminase were independent predictors of PFS. TACE followed by sorafenib significantly improved PFS and survival in patients with advanced HCC unresponsive to TACE.


In poetry, if meter has to help memory, it takes its time.
To test the idea that poetic meter emerged as a cognitive schema to aid verbal memory, we focused on classical Italian poetry and on three components of meter: rhyme, accent, and verse length. Meaningless poems were generated by introducing prosody-invariant non-words into passages from Dante's Divina Commedia and Ariosto's Orlando Furioso. We then ablated rhymes, modified accent patterns, or altered the number of syllables. The resulting versions of each non-poem were presented to Italian native speakers, who were then asked to retrieve three target non-words. Surprisingly, we found that the integrity of Dante's meter has no significant effect on memory performance. With Ariosto, instead, removing each component downgrades memory proportionally to its contribution to perceived metric plausibility. Counterintuitively, the fully metric versions required longer reaction times, implying that activating metric schemata involves a cognitive cost. Within schema theories, this finding provides evidence for high-level interactions between procedural and episodic memory.


The senescence-accelerated prone mouse (SAMP8): a model of age-related cognitive decline with relevance to alterations of the gene expression and protein abnormalities in Alzheimer's disease.
The senescence-accelerated mouse (SAM) is an accelerated aging model that was established through phenotypic selection from a common genetic pool of AKR/J strain of mice. The SAM model was established in 1981, including nine major senescence-accelerated mouse prone (SAMP) substrains and three major senescence-accelerated mouse resistant (SAMR) substrains, each of which exhibits characteristic disorders. Recently, SAMP8 have drawn attention in gerontological research due to its characteristic learning and memory deficits at old age. Many recent reports provide insight into mechanisms of the cognitive impairment and pathological changes in SAMP8. Therefore, this mini review examines the recent findings of SAMP8 mice abnormalities at the gene and protein levels. The genes and proteins described in this review are functionally categorized into neuroprotection, signal transduction, protein folding/degradation, cytoskeleton/transport, immune response and reactive oxygen species (ROS) production. All of these processes are involved in learning and memory. Although these studies provide insight into the mechanisms that contribute to the learning and memory decline in aged SAMP8 mice, higher throughput techniques of proteomics and genomics are necessary to study the alterations of gene expression and protein abnormalities in SAMP8 mice brain in order to more completely understand the central nervous system dysfunction in this mouse model. The SAMP8 is a good animal model to investigate the fundamental mechanisms of age-related learning and memory deficits at the gene and protein levels.


Construction and performance assessment of Recirculating packed bed biofilm reactor (RPBBR) for effective biodegradation of p-cresol from wastewater.
Wastewater containing excess phenolic compounds is considered a major environmental concern due to its adverse impacts on the ecosystem. In this work, an effort has been given to treat the p-cresol from wastewater using Recirculating Packed Bed Biofilm Reactor (RPBBR). The process parameters, namely inoculum dose, pH, and NaCl (w/v) concentration were optimized to enhance the specific growth and obtained to be 14 ml, 7.0, and 1% NaCl (w/100 ml), respectively. Maximum p-cresol removal efficiency of 99.36±0.2% was achieved at 100 mg L-1 of p-cresol. First-order rate constants were found to be 0.70 day-1 and 0.96 day-1 for batch and continuous mode, respectively. The intermediates were analysed using FT-IR and GC-MS analysis. Pseudomonas fluorescens was used to assess bacterial toxicity and observed that the toxicity was reduced in case of treated wastewater. Finally, the performance of continuous RPBBR was better than the batch mode.


Everything under control? The effects of age, gender, and education on trajectories of perceived control in a nationally representative German sample.
Perceived control is an important variable for various demands involved in successful aging. However, perceived control is not set in stone but rather changes throughout the life course. The aim of this study was to identify cross-sectional age differences and longitudinal mean-level changes as well as rank-order changes in perceived control with respect to gender and education. Furthermore, changes in income and health were analyzed to explain trajectories of perceived control. In a large and representative sample of Germans across all of adulthood, 9,484 individuals gave information about their perceived control twice over a period of 6 years. Using locally weighted smoothing (LOESS) curves and latent structural equation modeling, four main findings were revealed: (a) Perceived control increased until ages 30-40, then decreased until about age 60, and increased slightly afterwards. (b) The rank order of individuals in perceived control was relatively unstable, especially in young adulthood, and reached a plateau at about age 40. (c) Men perceived that they had more control than did women, but there were no gender differences in the development of perceived control. (d) Individuals with more education perceived that they had more control than those with less education, and there were slight differences in the development of perceived control dependent on education. Taken together, these findings offer important insights into the development of perceived control across the life span.


Care challenges of home health patients living with dementia: a pathway forward with palliative care.
Home health care (HHC) is a leading source of care support for older adults with serious illness, particularly patients living with dementia (PLWD). Demand for HHC is expected to continue to grow, driven by an aging population and preference for non-institutional care. HHC agencies are frequently under pressure to find effective approaches for improving care delivery and quality. One strategy that has the potential to improve the quality of life and patient satisfaction in HHC for PLWD is the integration of palliative care. Therefore, we sought to understand the experiences and needs of PLWD and their family caregivers specifically focusing on ways that HHC and palliative care may be integrated as part of the care transition from hospital to home, to better support PLWD and their families. We conducted a descriptive qualitative study focusing on the perspectives of patients, caregivers, and healthcare team members about palliative care delivery for patients receiving HHC. Interviews were audio-recorded and professionally transcribed. In this analysis, we specifically report on dementia-related content using an iterative, team-based thematic analysis approach. We identified three themes: 1) 'Living in the Whirlwind' which describes the many competing demands on caregivers time and the associated feeling of loss of control, 2) 'Thinking Ahead' which describes the importance of thinking beyond the day-to-day tasks to begin planning for the future, and 3) 'Pathways Forward' which describes the integration of palliative care into HHC to provide enhanced support for PLWD and their caregivers. In this qualitative study, our formative work identified the importance of providing anticipatory guidance (e.g., safety, advance care planning) coupled with emotional and pragmatic care supports (e.g., finding resources, navigating insurance) to sustain caregivers who are struggling with the whirlwind.


Fay-Prince trap baited with CO2 for monitoring adult abundance of Aedes sierrensis (Diptera: Culicidae).
The Fay-Prince trap augmented with carbon dioxide (F-P/CO2) collected high numbers of male and female Aedes sierrensis (Ludlow). The F-P/CO2 trap collected 15-20 times more males, but statistically similar numbers of females as did a rabbit-baited CO2 trap (R/CO2). Carbon dioxide was essential to the successful operation of the F-P/CO2 trap for the collection of male and female Ae. sierrensis. A repeated measures ANOVA with polynomial contrasts found no significant differences in the population trends of female Ae. sierrensis measured by the two traps. Trap location also was a major source of variability, with one of the four locations accounting for 50% of all Ae. sierrensis collected. These results indicated that the F-P/CO2 trap was a simple but effective method for sampling Ae. sierrensis.


The effects of dobutamine on cardiac sympathetic activity in patients with congestive heart failure.
The goal of this work was to study the effects of short-term infusion of dobutamine on efferent cardiac sympathetic activity. Increased efferent cardiac sympathetic activity is associated with poor outcomes in the setting of congestive heart failure (CHF). Dobutamine is commonly used in the therapy of decompensated CHF. Dobutamine, through its effects on excitatory beta-receptors, may increase cardiac sympathetic activity. Seven patients with normal left ventricular (LV) function and 13 patients with CHF were studied. A radiotracer technique was used to measure cardiac norepinephrine spillover (CANESP) before and during an intravenous infusion of dobutamine titrated to increase the rate of rise in LV peak positive pressure (+dP/dt) by 40%. Systemic arterial pulse pressure increased significantly in response to dobutamine in the normal LV function group (74 +/- 3 mm Hg to 85 +/- 3 mm Hg, p = 0.005) but remained unchanged in the CHF group. Dobutamine caused a significant decrease in LV end-diastolic pressure in the CHF group (14 +/- 2 mm Hg to 11 +/- 2 mm Hg, p = 0.02), an effect not observed in the normal LV group. In the normal LV function group, CANESP did not change in response to dobutamine (75 +/- 22 pmol/min vs. 72 +/- 22 pmol/min, p = NS). In contrast, dobutamine infusion was associated with a significant reduction in CANESP in patients with CHF (199 +/- 43 pmol/min to 128 +/- 30 pmol/min, p < 0.0009). Dobutamine infusion caused a significant sympatholytic response in patients with CHF. This sympathetic withdrawal response is probably related to reduction of LV filling pressures and/or activation of ventricular mechanoreceptors with dobutamine infusion.


Aprotinin, transfusions, and kidney injury in neonates and infants undergoing cardiac surgery.
A significantly increased risk of acute kidney injury (AKI) with the prophylactic use of aprotinin has been reported in adults undergoing cardiac surgery, but not in children. Blood product transfusions have also been shown to carry an independent risk of AKI. The present study assessed associations between AKI, aprotinin, and transfusions in neonates and infants undergoing cardiac surgery. All neonates and infants undergoing surgery with cardiopulmonary bypass over a 42 month period, before and after the withdrawal of aprotinin, were included retrospectively. AKI was assessed by the Acute-Kidney-Injury-Network classifications. A propensity score was used to balance treated and untreated groups. Three hundred and ninety patients received aprotinin and 568 patients did not. Inverse probability of treatment weighting resulted in good balance between groups for baseline and surgical characteristics. Controls underwent surgery with smaller bypass circuits and fewer transfusions. After adjustment for the use of miniaturized circuits and for the year of surgery, no significant association between the incidence of AKI, dialysis, and aprotinin was noted. Red blood cell transfusions were associated with an increased risk of AKI and dialysis: odds ratios (ORs) 1.64 (1.12-2.41) and 2.07 (1.13-3.73), respectively; as were fresh frozen plasma transfusions, ORs 2.28 (1.68-3.09) and 3.11 (1.95-4.97), respectively. Platelet transfusions were associated with an increased risk of dialysis: OR 2.20 (1.21-4.01). Blood product transfusions, but not the prophylactic use of aprotinin, are significantly associated with AKI after cardiac surgery in neonates and infants.


Sex- and mutation-specific p53 gain-of-function activity in gliomagenesis.
In cancer, missense mutations in the DNA-binding domain of TP53 are common. They abrogate canonical p53 activity and frequently confer gain-of-oncogenic function (GOF) through localization of transcriptionally active mutant p53 to non-canonical genes. We found that several recurring p53 mutations exhibit a sex difference in frequency in patients with glioblastoma (GBM). In vitro and in vivo analysis of three mutations, p53R172H, p53Y202C, and p53Y217C revealed unique interactions between cellular sex and p53 GOF mutations that determined each mutation's ability to transform male versus female primary mouse astrocytes. These phenotypic differences were correlated with sex- and p53 mutation- specific patterns of genomic localization to the transcriptional start sites of upregulated genes belonging to core cancer pathways. The promoter regions of these genes exhibited a sex difference in enrichment for different transcription factor DNA-binding motifs. Together, our data establish a novel mechanism for sex specific mutant p53 GOF activity in GBM with implications for all cancer.


Stalled but not forgotten: Bacterial exotoxins inhibit translation to activate NLRP1.
In this issue of JEM, companion articles from Pinilla et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20230104) and Robinson et al. (2023. J. Exp. Med.https://doi.org/10.1084/jem.20230105) demonstrate that ribotoxic stress induced by Pseudomonas aeruginosa and Corynebacterium diphtheriae EEF2-targeting exotoxins leads to NLRP1 inflammasome activation, representing a new mechanism of effector-triggered immunity.


Contribution of interleukin 17A to the development and regulation of allergic inflammation in a murine allergic rhinitis model.
Interleukin (IL) 17A, a key cytokine of T(H)17 cells, is a well-known proinflammatory cytokine. Despite the important role of T(H)17 cells in acute airway inflammation, the role of IL-17A in allergic rhinitis (AR) remains unclear. To investigate the role of IL-17A in the allergic response in AR. Wild-type BALB/c and IL-17A-deficient mice were immunized intraperitoneally and were challenged intranasally with ovalbumin. Allergic symptom scores, eosinophil infiltration, serum IgE level, and the levels of several cytokines in nasal lavage fluid and splenocyte supernatants were analyzed. IL-17A levels increased significantly more in ovalbumin-sensitized wild-type mice than in the negative control group. IL-17A-deficient mice showed a significant decrease in allergic symptoms, serum IgE levels, and eosinophil infiltration into the nasal mucosa compared with wild-type mice. IL-17A-deficient mice also showed decreased histamine and cysteinyl leukotriene release. Bone marrow-derived mast cells from IL-17A-deficient mice showed significantly lower degranulation and secretion of tumor necrosis factor α. Moreover, IL-17A deficiency attenuated the IL-5 level in nasal lavage fluid and its production in response to ovalbumin but did not increase interferon γ production and its level in nasal lavage fluid. In addition, secretion of IL-17A from spleen cells induced the expression of proinflammatory cytokine messenger RNA in macrophages. The mean level of proinflammatory cytokines, including tumor necrosis factor α and IL-17, decreased in IL-17A-deficient mice. These results suggest that IL-17A may partly contribute to the development of nasal allergic inflammation in an AR animal model and regulate AR via the activation of proinflammatory cytokines and modulation of T(H)2 cytokine.


Neuroprotective effects of Jie-du-huo-xue decoction on microglia pyroptosis after cerebral ischemia and reperfusion--From the perspective of glial-vascular unit.
Ischemic stroke poses a serious risk to public health and quality of life. Jie-Du-Huo-Xue decoction (JDHXD) is a classical and well-known Chinese formula for stroke treatment, but the pharmacological mechanism is still unclear. This study aims to investigate the mechanism underlying microglial pyroptosis and polarization, as well as the potential efficacy of JDHXD against cerebral ischemia-reperfusion injury (CIRI). Models of CIRI were established by the middle cerebral artery occlusion/reperfusion (MCAO/R) method in rats. In the first stage, 36 SD rats were randomly divided into sham group, I/R group, JDHXD-L group (5.36 g/kg/day), JDHXD-M group (10.71 g/kg/day), JDHXD-H group (21.42 g/kg/day), and positive drug edaravone group. The effectiveness of JDHXD on CIRI was confirmed by neurological function testing and cerebral infarct measuring. The best dose (JDXHD-M) was subsequently chosen to perform the tests that followed. In the second stage, 36 SD rats were randomly divided into the sham group, the I/R group, and the JDHXD-M group. Detection of nerve damage using Nissl staining, proteins of pyroptosis, Iba-1, and NeuN expressions were detected by western blotting, and proteins of microglial pyroptosis and M1/M2 phenotypic polarization were detected by immunofluorescence. In rats after CIRI, JDHXD significantly reduced neurological impairment and cerebral infarction. In addition, JDHXD facilitated the M1-to-M2 transition of microglia in order to minimize neuroinflammation and improve anti-inflammatory repair. In addition, JDXHD inhibited microglial pyroptosis by blocking the cleavage of caspase-1 P10 and gasdermin D, hence reducing neuronal damage and enhancing neuronal survival following reperfusion. Interestingly, JDHXD also demonstrated a protective effect on the glial-vascular unit (GVU). Our investigation demonstrated that JDHXD exerted a GVU-protective effect on CIRI rats by decreasing neuroinflammation-associated microglial pyroptosis, suppressing microglial M1 activation, and promoting microglial M2 activation.


Comparative study of fibroblast growth factor 2 and ofloxacin ear drops for repairing large traumatic perforations: A randomized controlled study.
The objective of this study was to compare the healing outcome of fibroblast growth factor 2 (FGF2), ofloxacin ear drops (OFLX) and spontaneous healing for repairing large traumatic tympanic membrane (TM) perforations. A total of 75 traumatic large perforations with >1/4 of TM were randomly divided into FGF2 (n = 25), OFLX (n = 25), and spontaneous healing (n = 25) groups. The closure rates, closure times, and hearing gains were compared at 3 months. At 2 weeks after treatment, the closure rate was 95.8 % in the FGF2 group, 96.0 % in the ofloxacin ear drops group, and 14.3 % in the spontaneous healing group (P < 0.01), respectively. At 3 months after treatment, the closure rate was 100 % in the FGF2 group, 100 % in the OFLX group, and 85.7 % in the spontaneous healing group, no among-group differences were significant (P > 0.05). The mean closure time was 9.69 ± 2.46 days in the FGF2 group, 9.45 ± 2.32 days in the OFLX group, and 30.94 ± 8.95 days in the spontaneous healing group (P < 0.01). The mean ABG was 10.37 ± 2.51 dB for the FGF2 group, 11.01 ± 1.31 dB for the OFLX group, and 10.86 ± 1.94 dB for the spontaneous healing group, no significant difference was found among three groups (P > 0.05). This study suggested that both FGF2 and OFLX significantly shortened the mean closure time and improved the closure rate compared with spontaneous healing for repairing large traumatic perforations, while the healing outcome wasn't significantly different among FGF2 and OFLX groups.


Genome-wide study of early and severe childhood asthma identifies interaction between CDHR3 and GSDMB.
Asthma with severe exacerbation is one of the most common causes of hospitalization among young children. Exacerbations are typically triggered by respiratory infections, but the host factors causing recurrent infections and exacerbations in some children are poorly understood. As a result, current treatment options and preventive measures are inadequate. We sought to identify genetic interaction associated with the development of childhood asthma. We performed an exhaustive search for pairwise interaction between genetic single nucleotide polymorphisms using 1204 cases of a specific phenotype of early childhood asthma with severe exacerbations in patients aged 2 to 6 years combined with 5328 nonasthmatic controls. Replication was attempted in 3 independent populations, and potential underlying immune mechanisms were investigated in the COPSAC2010 and COPSAC2000 birth cohorts. We found evidence of interaction, including replication in independent populations, between the known childhood asthma loci CDHR3 and GSDMB. The effect of CDHR3 was dependent on the GSDMB genotype, and this interaction was more pronounced for severe and early onset of disease. Blood immune analyses suggested a mechanism related to increased IL-17A production after viral stimulation. We found evidence of interaction between CDHR3 and GSDMB in development of early childhood asthma, possibly related to increased IL-17A response to viral infections. This study demonstrates the importance of focusing on specific disease subtypes for understanding the genetic mechanisms of asthma.


Factors governing urinary tract stone disease.
Urinary stone formation depends on the degree of saturation of the urine with respect to potential stone-forming substances. Urine contains a range of electrolytes which ionise to different and variable degrees and which interact with one another in ways which influence their solubilities. These ionisations are themselves influenced by the pH of the urine which is another variable factor. Urinary organic molecules, which may or may not ionise and which may bear surface charges, also influence the solubility of the low molecular weight stone-constituents. Some other substances in the urine, such as glycosaminoglycans, can modify the ability of inorganic micro-crystals to aggregate and form stones. Environmental factors, other urinary tract pathology and genetic influences all predispose to urolithiasis, but many cases lack either an identifiable specific cause or the presence of recognisable risk factors. In the risk factor model of calcium stone formation there are pre-renal risk factors which lead to urinary risk factors and hence to the chemical risk factors of supersaturation and decreased ability to inhibit crystallisation. There are, in addition to these general factors which may act synergistically to produce urinary stones, several specific single enzyme defects which alter the urinary composition in such a way as to produce stones of a highly characteristic composition.


Risk factors for peripheral intravascular catheter-related phlebitis in critically ill patients: analysis of 3429 catheters from 23 Japanese intensive care units.
Phlebitis is an important complication occurring in patients with peripheral intravascular catheters (PIVCs). The risk factors for phlebitis in the intensive care unit (ICU) was examined. A secondary analysis of a prospective multicenter cohort study was conducted, involving 23 ICUs in Japan-the AMOR-VENUS study. Consecutive patients aged ≥ 18 years admitted to the ICU with newly inserted PIVCs after ICU admission were enrolled. Characteristics of the ICU, patients, PIVCs, and the drugs administered via PIVCs were recorded. A marginal Cox regression model was used to identify the risk factors associated with phlebitis. A total of 2741 consecutive patients from 23 ICUs were reviewed for eligibility, resulting in 1359 patients and 3429 PIVCs being included in the analysis population. The median dwell time was 46.2 h (95% confidence interval [CI], 21.3-82.9). Phlebitis occurred in 9.1% (95% CI, 8.2-10.1%) of catheters (3.5 cases/100 catheter days). The multivariate analysis revealed that the only factors that increased the risk of developing phlebitis were drugs administered intravenously. This study included 26 drugs, and 4 were associated with increased phlebitis: nicardipine (HR, 1.85; 95% CI, 1.29-2.66), noradrenaline (HR, 2.42; 95% CI, 1.40-4.20), amiodarone (HR, 3.67; 95% CI, 1.75-7.71) and levetiracetam (HR, 5.65; 95% CI, 2.80-11.4). Alternatively, factors significantly associated with a reduced risk of phlebitis were: standardized drug administration measures in the ICU (HR, 0.35; 95% CI, 0.17-0.76), 30≤ BMI (HR, 0.43; 95% CI, 0.20-0.95), catheter inserted by a doctor as nurse reference (HR, 0.55; 95% CI, 0.32-0.94), and upper arm insertion site as forearm reference (HR, 0.52; 95% CI, 0.32-0.85). The nitroglycerin was associated with a reduced phlebitis risk (HR, 0.22; 95% CI, 0.05-0.92). Various factors are involved in the development of phlebitis caused by PIVCs in critically ill patients, including institutional, patient, catheter, and drug-induced factors, indicating the need for appropriate device selection or models of care in the ICU. UMIN-CTR, the Japanese clinical trial registry (registration number: UMIN000028019, July 1, 2017).


The many faces of c-MYC.
The proto-oncogene c-MYC is implicated in various physiological processes-cell growth, proliferation, loss of differentiation, and cell death (apoptosis). Oncogenic c-MYC implies constitutive or deregulated expression of c-MYC and is associated with many human cancers often with poor prognosis. Recently, c-MYC has been implicated in the loss and dysfunction of insulin-producing beta cells in diabetes. Intriguingly, this raises the possibility that c-Myc may be a key contributor to disease, not only by deregulating cell proliferation, which is well established, but also by virtue of its opposing role in engendering apoptosis. However, given the fact that human diseases at diagnosis are generally advanced and pathologically complex, it is generally difficult to attribute a specific pathogenic role to c-MYC, or indeed any given single factor, or to assess the potential of therapies targeting individual such factors. Regulatable transgenic mouse models have shed light on these issues, have influenced our thinking about cancer, and have provided encouragement for the future development of cancer therapies based on targeting individual oncogenes such as c-MYC. Although still in its infancy, encouraging results have been reported for several approaches using gene targeting to interfere with c-MYC expression or activity both in vitro and in vivo.


Disrupted axon-glia interactions at the paranode in myelinated nerves cause axonal degeneration and neuronal cell death in the aged Caspr mutant mouse shambling.
Emerging evidence suggests that axonal degeneration is a disease mechanism in various neurodegenerative diseases and that the paranodes at the nodes of Ranvier may be the initial site of pathogenesis. We investigated the pathophysiology of the disease process in the central and peripheral nervous systems of a Caspr mutant mouse, shambling (shm), which is affected by disrupted paranodal structures and impaired nerve conduction of myelinated nerves. The shm mice manifest a progressive neurological phenotype as mice age. We found extensive axonal degeneration and a loss of neurons in the central nervous system and peripheral nervous system in aged shm mice. Axonal alteration of myelinated nerves was defined by abnormal distribution and expression of neurofilaments and derangements in the status of phosphorylated and non/de-phosphorylated neurofilaments. Autophagy-related structures were also accumulated in degenerated axons and neurons. In conclusion, our results suggest that disrupted axon-glia interactions at the paranode cause the cytoskeletal alteration in myelinated axons leading to neuronal cell death, and the process involves detrimental autophagy and aging as factors that promote the pathogenesis.


Development of novel 4-aminopyridine derivatives as potential treatments for neurological injury and disease.
The amine position of the K+ channel blocker 4-aminopyridine was functionalized to form amide, carbamate and urea derivatives in an attempt to identify novel compounds which restore conduction in injured spinal cord. Eight derivatives were tested in vitro, using a double sucrose gap chamber, for the ability to restore conduction in isolated, injured guinea pig spinal cord. The methyl, ethyl and t-butyl carbamates of 4-aminopyridine induced an increase in the post injury compound action potential. The methyl and ethyl carbamates were further tested in an in vivo model of spinal cord injury. These results represent the first time that 4-aminopyridine has been derivatized without losing its ability to restore function in injured spinal cord tissue.


Severe pathological changes in the blood and organs of SD rats stung by honeybees.
With the development of beekeeping, the risk of bee stings in humans is increasing. Severe and life-threatening toxic reactions can occur after multiple bee stings, and their pathogenesis has not been elucidated. To understand the effect of multiple bees (Apis mellifera) stings on the organism in a short period, we stung rats once and five times, respectively. Serum and organs were obtained after 3 h for analysis. The results indicated that skin erythema was more pronounced and hemolysis was more severe as the number of puncture wounds increased. After being stung by five bees, rats had dramatically higher serum levels of direct bilirubin, aspartate aminotransferase, creatine kinase and lactate dehydrogenase, producing more differential metabolites that affected mainly four metabolic pathways. In addition, the liver, kidney and heart showed significant congestion and inflammation. This study helps explain the organism's clinical response to bee venom and may be valuable in treating toxic reactions following bee stings.


Oxidative torrefaction of microalga Nannochloropsis Oceanica activated by potassium carbonate for solid biofuel production.
Oxidative torrefaction is a promising way for biomass upgrading and solid biofuel production. Alkali metals are considered to be efficient activators for enhancing biofuel upgrading during the thermal reaction process. Herein, the microalga Nannochloropsis Oceanica is selected as the feedstock for assessing potassium carbonate activated effect on solid biofuel production through oxidative torrefaction. The potential of potassium carbonate on microalgal biofuel properties upgrading is deeply explored. SEM observation and BET analysis show that torrefied microalgae can be transformed from a spherical structure with wrinkles to smaller particles with larger surface areas and higher total pore volumes, implying that potassium carbonate is a promising porogen. Moreover, potassium carbonate can significantly change the DTG curve at the temperatures of 250 °C and 300 °C from one peak to two peaks, inferring that the activated effect of potassium carbonate occurs on the torrefied microalgae. 13C NMR analysis reveals that the microalgal components significantly change as the torrefaction severity increases, with the decomposition of carbohydrate and protein components. When the potassium carbonate ratio increases from 0:1 to 1:1, the graphitization degree increase from 3.065 to 1.262, along with the increase in the HHV of solid biofuel from 25.024 MJ kg-1 to 31.890 MJ kg-1. In total, this study has comprehensively revealed the activated effect of potassium carbonate on improving the properties of microalgal solid biofuel.


Correction: Pomalidomide, bortezomib, and low-dose dexamethasone in lenalidomide-refractory and proteasome inhibitor-exposed myeloma.
Following the publication of this article, the authors noted that the pomalidomide dose for the additional SC cohort in Fig. 1 was incorrectly listed. The correct dose for pomalidomide in the additional SC cohort should be the maximum tolerated dose of 4 mg/day, not 2 mg/day as listed in the original Fig. 1. The authors apologize for any inconvenience caused.


Construction and screening of an antigen-derived peptide library displayed on yeast cell surface for CD4+ T cell epitope identification.
Identification of T cell epitopes is a critical, but often difficult step in studying T cell function and developing peptide-based vaccines and immunotherapies. Unlike antibodies that recognize free soluble antigens, T cell receptor (TCR) recognizes its epitope bound to major histocompatibility complex (MHC) expressed on antigen presenting cells (APCs). In addition, the examination of T cell epitope activity requires the use of professional APCs, which are difficult to isolate, expand, and maintain. To address these issues, we have developed a facile, accurate, and high-throughput method for T cell epitope mapping by screening antigen-derived peptide libraries in complex with MHC protein displayed on yeast cell surface. Here, we use hemagglutinin and influenza A virus X31/A/Aichi/68 as examples to describe the key steps in identification of CD4+ T cell epitopes from a single antigenic protein and the entire genome of a pathogen, respectively. Methods for single-chain peptide-MHC complex vector design, yeast surface display, peptide library generation in Escherichia coli, and functional screening in Saccharomyces cerevisiae are discussed.


An analogue of piperonyl butoxide facilitates the characterisation of metabolic resistance.
Previous work has demonstrated that piperonyl butoxide (PBO) not only inhibits microsomal oxidases but also resistance-associated esterases. The ability to inhibit both major metabolic resistance enzymes makes it an ideal synergist to enhance xenobiotics but negates the ability to differentiate which enzyme group is responsible for conferring resistance. This study examines an analogue that retains the ability to inhibit esterases but is restricted in its ability to act on microsomal oxidases, thus allowing an informed decision on resistance enzymes to be made when used in conjunction with the parent molecule. Using examples of resistant insects with well-characterised resistance mechanisms, a combination of PBO and analogue allows identification of the metabolic mechanism responsible for conferring resistance. The relative potency of PBO as both an esterase inhibitor and an oxidase inhibitor is also discussed.


Low-intensity pulsed ultrasound (LIPUS) may prevent polyethylene induced periprosthetic osteolysis in vivo.
We investigated the effect of local low-intensity pulsed ultrasound (LIPUS) on polyethylene debris induced periprosthetic osteolysis. The periprosthetic osteolysis model was made by injecting endotoxin-free pure polyethylene particles into the distal part of the femur canal and inserting a stainless steel plug into this femur. The effects of polyethylene and LIPUS were assessed histologically and by the shear strength test and periprosthetic bone mineral density (BMD) test. Sixteen rabbits received a stainless steel plug on one side and both polyethylene and a stainless steel plug on the other side. Three months later, the side that received polyethylene showed periprosthetic osteolysis. Subsequently, another 16 rabbits received polyethylene plus local LIPUS (200 mW/cm(2) for 20 min daily) on one side and polyethylene alone on the other side. Three months later, LIPUS effectively prevented the periprosthetic osteolysis caused by polyethylene in this rabbit model.


Behavioral and neurocognitive effects of judo training on working memory capacity in children with ADHD: A randomized controlled trial.
Children with Attention Deficit Hyperactivity Disorder (ADHD) face deficits in working memory capacity that often persist into adulthood. In healthy peers, exercise targeting motor skill acquisition benefits visuospatial working memory, but its potential to reduce ADHD-related deficits remains unclear. We investigated the effect of a judo training program targeting motor skills on behavioral and neurocognitive indices of working memory capacity in children with ADHD. Children with ADHD aged 8 to 12 years (N = 57) were randomly allocated to a judo training group and a wait-list control group. The training program encompassed 120 min of judo per week over three months. Before and after the intervention period, participants completed a bilateral Change Detection task with low and high memory load conditions and the Movement Assessment Battery for Children-2 (MABC-2). The contralateral delay activity (CDA) elicited by the cognitive task was recorded using electroencephalography. Compared to the control group, the judo training group showed a higher K-score on the Change Detection task and an increased negativity of the CDA on the high load condition following the intervention, when pretest scores (and confounders) were accounted for. In contrast, no group differences were found for MABC-2 score. In children with ADHD, judo training may complement the pharmacological treatment by increasing the effectiveness of working memory maintenance processes. On a behavioral level, this improvement is accompanied with an increased capacity to store visuospatial information.


Bubble packing, eccentricity, and notochord development.
This paper develops a theoretical basis for the observed relationship between cell arrangements in notochords and analog physical models, and the eccentricity of their cross sections. Three models are developed and analyzed, of the mechanics of cell packing in sheaths. The key ratios governing the packing patterns and eccentricity are cells per unit length λ, tension ratio Γ, and eccentricity e. For flexible and semi-flexible sheaths, the optimal packing pattern shifts from "bamboo", with a symmetric cross section, to "staircase", with an eccentric cross section, at a critical value λ = 1.13. In rigid tubes, this threshold is lowered as imposed eccentricity is increased. Patterns can be observed which are not optimal; pattern transitions may occur below or above the critical λ values. The eccentricity of staircase patterns in flexible and semi-flexible tubes is found to be dependent on the tension ratio Γ, increasing as sheath tension decreases relative to interior cell tension. A novel "serpentine" packing pattern appears for low Γ near the critical λ. The developmental utility of enforcing notochord eccentricity is discussed, as well as potential mechanisms for such control.


Effect of N omega-nitro-L-arginine on working memory of rats in eight-arm maze task.
To study the effect of N omega-nitro-L-arginine (NNA) (a NO synthase inhibitor) on memory in the rats. A delayed non-match-to-sample (DNMTS) eight-arm maze task was used to study spatial working memory. Intraperitoneal injection of NNA 100 mg kg-1 before the trial or at the start of the delay did not affect the accuracy, while pretraining administration of scopolamine 0.25 mg kg-1 produced impairment in mnemonic performance as evidenced by fewer correct choices after the delay and more total errors to complete the task. Intracerebroventricular infusion of NNA (10, 50, 100 nmol) did not affect the accuracy. A single ip or icv injection of NNA is not sufficient to alter the memory formation and use in this DNMTS eight-arm maze task.


Resembling a "natural formation pattern" of chlorinated dibenzo-p-dioxins by varying the experimental conditions of hydrothermal carbonization.
Until several years ago dioxins were considered as just an unwanted by product of anthropogenic activities and stigmatized as the symbol of man-made environmental pollution. Natural processes, such as forest fires, can emit dioxins, but compared to industrial processes, usually very low quantities are emitted. However after a case of food contamination occurred in the United States of America in 1996 caused by kaolinitic clay a discussion on the provenience started. Besides the relatively high concentration also an unusual PCDD/F distribution pattern was found in these ball clay samples. This specific pattern related to none of the known anthropogenic sources for these contaminants and, in relation to a supposed natural formation, later it was named "natural formation pattern". Hydrothermal carbonization (HTC) can transform biomass within hours into a brown coal-like product which resembles naturally occurring coal formation. HTC can also transform an already present PCDD/F contamination in a way to obtain a "natural formation pattern" characterized by an unusual high ratio between 1,2,3,7,8,9-HxCDD and 1,2,3,6,7,8-HxCDD and the absence of almost all chlorinated dibenzofurans. By varying the experimental conditions of the HTC process applied to sewage sludge samples contaminated with PCDD/Fs from anthropogenic sources, beside the "natural formation pattern" at a temperatures of 255 °C, a remarkable increase of the toxicity based on WHO-TEQ was observed.


Pandemic flu: are we properly prepared?
This paper presents the proceedings of the 2006 conference 'Pandemic flu: Are we properly prepared?', held in London. This conference sought to provide an overview of the preparatory steps necessary if a potential UK pandemic influenza (flu) outbreak is to be mitigated. Topics included the history of pandemic flu, research and development, antiviral drugs, clinical assessment of flu, and critical care contingency planning. The ethical dilemmas relating to a flu pandemic were also discussed.


Galectin-1-dependent ceRNA network in HRMECs revealed its association with retinal neovascularization.
Retinal neovascularization (RNV) is a leading cause of blindness worldwide. Long non-coding RNA (lncRNA) and competing endogenous RNA (ceRNA) regulatory networks play vital roles in angiogenesis. The RNA-binding protein galectin-1 (Gal-1) participates in pathological RNV in oxygen-induced retinopathy mouse models. However, the molecular associations between Gal-1 and lncRNAs remain unclear. Herein, we aimed to explore the potential mechanism of action of Gal-1 as an RNA-binding protein. A comprehensive network of Gal-1, ceRNAs, and neovascularization-related genes was constructed based on transcriptome chip data and bioinformatics analysis of human retinal microvascular endothelial cells (HRMECs). We also conducted functional enrichment and pathway enrichment analyses. Fourteen lncRNAs, twenty-nine miRNAs, and eleven differentially expressed angiogenic genes were included in the Gal-1/ceRNA network. Additionally, the expression of six lncRNAs and eleven differentially expressed angiogenic genes were validated by qPCR in HRMECs with or without siLGALS1. Several hub genes, such as NRIR, ZFPM2-AS1, LINC0121, apelin, claudin-5, and C-X-C motif chemokine ligand 10, were found to potentially interact with Gal-1 via the ceRNA axis. Furthermore, Gal-1 may be involved in regulating biological processes related to chemotaxis, chemokine-mediated signaling, the immune response, and the inflammatory response. The Gal-1/ceRNA axis identified in this study may play a vital role in RNV. This study provides a foundation for the continued exploration of therapeutic targets and biomarkers associated with RNV.


Global patterns of predator diversity in the open oceans.
The open oceans comprise most of the biosphere, yet patterns and trends of species diversity there are enigmatic. Here, we derive worldwide patterns of tuna and billfish diversity over the past 50 years, revealing distinct subtropical "hotspots" that appeared to hold generally for other predators and zooplankton. Diversity was positively correlated with thermal fronts and dissolved oxygen and a nonlinear function of temperature (approximately 25 degrees C optimum). Diversity declined between 10 and 50% in all oceans, a trend that coincided with increased fishing pressure, superimposed on strong El Niño-Southern Oscillation-driven variability across the Pacific. We conclude that predator diversity shows a predictable yet eroding pattern signaling ecosystem-wide changes linked to climate and fishing.


Pentoxifylline reduces the inflammatory process in diabetic rats: relationship with decreases of pro-inflammatory cytokines and inducible nitric oxide synthase.
Studies suggest that inflammation is a key factor in the pathogenesis of diabetes mellitus. Pro-inflammatory cytokines, such as IL-6 and TNF-alpha, are produced by adipose tissue in large quantities, in obese and especially in diabetic individuals. Pentoxifylline (PTX) is a non-selective phosphodiesterase inhibitor with anti-inflammatory and antioxidant actions that may contribute to alleviate diabetes side effects, as neuropathy, retinopathy and nephropathy. This study aims to investigate PTX anti-inflammatory effects on the carrageenan-induced paw edema model, in alloxan-induced diabetic rats. Diabetic animals (male Wistar rats, 200-250 g) were daily treated with PTX (25, 50, 100 mg/kg, p.o.), glibenclamide (GLI, 5 mg/kg, p.o., as reference) or water, for 5 days. Afterwards, carrageenan-treated paws were dissected, their skin removed and the tissue used for preparation of homogenates and measurements of IL-6 and TNF-alpha by Elisa. Serum levels of nitrite were also determined and paw slices used for iNOS immunohistochemistry assays. We showed that diabetic rats presented an amplification of the inflammatory response, as related to non-diabetic rats, what was evident 48 h after the edema-induction. The PTX-treatment of diabetic rats reduced glycemia (as related to untreated-diabetic ones) and the paw edema. It also brought edema volumes to values similar to those of non-diabetic rats, at the same observation time. The increased TNF-alpha and IL-6 levels in paws of untreated-diabetic rats were reduced in diabetic animals after PTX treatments. Besides, the increased levels of nitrite in the serum of diabetic rats were also decreased by PTX. Furthermore, a higher number of iNOS immunostained cells was demonstrated in paw tissues from untreated-diabetic rats, as related to those of PTX-treated diabetic animals. Our results show that PTX reduces inflammatory parameters, as pro-inflammatory cytokines and iNOS expression, indicating the potential benefit of the drug for the treatment of diabetes and related pathologic conditions.


ATP modulates the activity of the voltage-gated proton channel through direct binding interaction.
ATP is an important molecule implicated in diverse biochemical processes, including the modulation of ion channel and transporter activity. The voltage-gated proton channel (Hv1) controls proton flow through the transmembrane pathway in response to membrane potential, and various molecules regulate its activity. Although it is believed that ATP is not essential for Hv1 activity, a report has indicated that cytosolic ATP may modulate Hv1. However, the detailed molecular mechanism underlying the effect of ATP on Hv1 is unknown, and whether ATP is involved in the physiological regulation of Hv1 activity remains unclear. Here, we report that cytosolic ATP is required to maintain Hv1 activity. To gain insight into the underlying mechanism, we analysed the effects of ATP on the mouse Hv1 channel (mHv1) using electrophysiological and microscale thermophoresis (MST) methods. Intracellular ATP accelerated the activation kinetics of mHv1, thereby increasing the amplitude of the proton current within the physiological concentration range. The increase in proton current was reproduced with a non-hydrolysable ATP analogue, indicating that ATP directly influences Hv1 activity without an enzymatic reaction. The direct molecular interaction between the purified mHv1 protein and ATP was analysed and demonstrated through MST. In addition, ATP facilitation was observed for the endogenous proton current flowing through Hv1 in the physiological concentration range of ATP. These results suggest that ATP influences Hv1 activity via direct molecular interactions and is required for the physiological function of Hv1. KEY POINTS: We found that ATP is required to maintain the activity of voltage-gated proton channels (Hv1) and investigated the underlying molecular mechanism. Application of intracellular ATP increased the amplitude of the proton current flowing through Hv1, accompanied by an acceleration of activation kinetics. The direct interaction between purified Hv1 protein and ATP was quantitatively analysed using microscale thermophoresis. ATP enhanced endogenous proton currents in breast cancer cell lines. These results suggest that ATP influences Hv1 activity via direct molecular interactions and that its functional characteristics are required for the physiological activity of Hv1.


Urinary excretion of epidermal growth factor in living human kidney donors and their recipients.
Epidermal growth factor (EGF) is a growth-promoting peptide that is synthesized in the distal tubules of the kidney and excreted in urine. EGF has been suggested to play a role in the repair after renal tissue damage, as well as in compensatory growth of the remaining kidney after uninephrectomy. The present study examined the urinary EGF excretion after uninephrectomy and transplantation among relatives. The urinary EGF excretion rate and the glomerular filtration rate (GFR) were followed for 26-54 days in 16 healthy kidney donors and nine recipients. After uninephrectomy the median urinary EGF excretion rate in the donors was not 50% of the pre-operative value, but around 65% (95% confidence limits of the median on the fifth post-operative day: 59-72%). This suggests that there is a compensatory increase in the EGF excretion rate from the remaining kidney of around 30% after uninephrectomy. A similar compensatory increase was demonstrated for GFR, indicating that the compensatory changes in EGF excretion rate and GFR might be correlated. In the transplanted kidneys, GFR was consistently around 15% lower and EGF excretion rate around 40% lower than in the corresponding kidneys remaining in the donors. This might reflect ischaemic and drug-induced damage of the transplanted kidneys. The present study demonstrated a compensatory increase of around 30% in urinary EGF excretion from the remaining kidney after uninephrectomy in healthy humans. Whether EGF plays a role in the adaptive processes in the remaining kidney or whether changes in EGF excretion are merely of a secondary nature is still uncertain.


The prognostic value of the Naples prognostic score for patients with non-small-cell lung cancer.
The Naples prognostic score (NPS) is an effective inflammatory and nutritional scoring system widely applied as a prognostic factor in various cancers. We aimed to analyze the prognostic value of the NPS in patients diagnosed with non-small-cell lung cancer (NSCLC). We prospectively collected 395 patients diagnosed with NSCLC between January 2016 and December 2018 in two university-affiliated hospitals. Patients were divided into three groups according to their pretreatment NPS (Group 0: NPS = 0; Group 1: NPS = 1-2; Group 2: NPS = 3-4). Kaplan-Meier survival curves indicated that patients with higher NPS had a poorer overall survival (OS) and progress-free survival (PFS) (both P < 0.05). NPS was further confirmed as an independent prognostic factors of OS and PFS by multivariable survival analysis (both P < 0.05). Furthermore, stratifying by TNM stage, NPS also has significant predictive performance for OS and PFS in both early (I-IIIA) and advanced (IIIB-IV) stage NSCLC (all P < 0.05). The time-dependent receiver operating characteristic curve analysis demonstrated that NPS was more superior to other prognostic factors in predicting OS and PFS. In conclusion, NPS may serve as an effective indicator to predict OS and PFS in NSCLC patients regardless of TNM stage.


Liver metastases from pancreatic adenocarcinoma: MR imaging characteristics.
To describe the magnetic resonance imaging spectrum of appearances of liver metastases from pancreatic ductal adenocarcinoma. We retrospectively evaluated the MRI exams performed between July 1996 and August 2001 in all patients who had liver metastases from pancreatic adenocarcinoma and histopathologic diagnosis from either the primary pancreatic tumor, liver metastases, or both. Sixteen patients were included in the study. All MR studies were performed at 1.5 T with a standard protocol including T1- and T2-weighted images and serial post-gadolinium spoiled gradient echo (SGE) images. Location, size, number, signal characteristics on T1- and T2-weighted images, and pattern of enhancement on serial gadolinium-enhanced SGE images were assessed. The diameter of metastases ranged from a few millimetres to 4 cm, and 12 patients (75%) had only lesions of 1.5 cm or less. Capsular-based liver metastases were found in 13 patients (81%) and three patients had only capsular-based lesions with a diameter under 1.5 cm. Hypervascular lesions were found in six patients (38%) and hypovascular lesions in 10 patients (62%). Perilesional enhancement was present in 10 patients (62%), with six patients (38%) having ring perilesional enhancement and eight patients (50%) having wedge-shaped perilesional enhancement. On MR imaging, hepatic metastases from pancreatic adenocarcinoma show a range of enhancement patterns. Hypervascular metastases are not rare. Capsular based distribution, small diameter, and perilesional enhancement are common features. This retrospective study describes the MR imaging spectrum of appearances of liver metastases from pancreatic adenocarcinoma in patients with histopathologic confirmation of the diagnosis.


Treatment of Posterior Cruciate Ligament Tibial Avulsion: A New Modified Open Direct Lateral Posterior Approach.
The optimal operative technique for the treatment of the tibial-side avulsion injuries of the posterior cruciate ligament (PCL) is debatable. This study was aimed to evaluate the postoperative outcomes and complications if any after an open direct, posterolateral approach using cannulated cancellous screw fixation of a PCL tibial avulsion. From January 2016 to June 2018, 17 patients (14 males and 3 females) with PCL avulsion fraction treatment-who underwent open reduction and internal fixation using cannulated cancellous screws-were included in this prospective study. A direct posterolateral approach in the prone position was used in all cases. The Lysholm's knee score and International Knee Documentation Committee (IKDC) score were assessed preoperatively and during regular follow-up examinations for at least 1 year (12-20 months) postoperatively. All patients had fracture union and all of their knees were stable upon physical examination. No nerve or blood vessel injuries occurred. The mean Lysholm's scores and mean IKDC scores were improved significantly at the last follow-up. This study provides evidence that open direct posterolateral approach may be reliable for the treatment of tibial-sided bony PCL avulsion fractures. This approach can provide direct visualization of the posterior capsule and PCL avulsion site associated with good reduction and stable fixation, easy application of the screws directly from posterior to anteriorly without extensive soft tissue damage. Nevertheless, long-term follow-up is recommended.


Usefulness of the left ventricular myocardial contraction fraction in healthy men and women to predict cardiovascular morbidity and mortality.
We sought to determine whether depressed myocardial contraction fraction (MCF; ratio of left ventricular [LV] stroke volume to myocardial volume) predicts cardiovascular disease (CVD) events in initially healthy adults. A subset (n = 318, 60 ± 9 years old, 158 men) of the Framingham Heart Study Offspring cohort free of clinical CVD underwent volumetric cardiovascular magnetic resonance imaging in 1998 through 1999. LV ejection fraction (EF), mass, and MCF were determined. "Hard" CVD events consisted of cardiovascular death, myocardial infarction, stroke, or new heart failure. A Cox proportional hazards model adjusting for Framingham Coronary Risk Score was used to estimate hazard ratios for incident hard CVD events for gender-specific quartiles of MCF, LV mass, and LVEF. The lowest quartile of LV mass and highest quartiles of MCF and EF served as referents. Kaplan-Meier survival plots and log-rank test were used to compare event-free survival. MCF was greater in women (0.58 ± 0.13) than in men (0.52 ± 0.11, p <0.01). Nearly all participants (99%) had EF ≥0.55. During an up to 9-year follow-up (median 5.2), 31 participants (10%) developed an incident hard CVD event. Lowest-quartile MCF was 7 times more likely to develop a hard CVD (hazard ratio 7.11, p = 0.010) compared to the remaining quartiles, and increased hazards persisted even after adjustment for LV mass (hazard ratio 6.09, p = 0.020). The highest-quartile LV mass/height 2.7 had a nearly fivefold risk (hazard ratio 4.68, p = 0.016). Event-free survival was shorter in lowest-quartile MCF (p = 0.0006) but not in lowest-quartile LVEF. In conclusion, in a cohort of adults initially without clinical CVD, lowest-quartile MCF conferred an increased hazard for hard CVD events after adjustment for traditional CVD risk factors and LV mass.


Short-term variability of plant populations within a regularly disturbed habitat.
The changing populations of weeds during 13 years of the Broadbalk continuous wheat experiment were analysed to investigate the extent of differences in shortterm variability of cover between species. The data were from two sections of the experiment where winter wheat was grown continuously under herbicide treatment for 13 and 6 years respectively. Logistic regressions were fitted to the data. Equisetum arvense showed significant long-term increases on both sections; long-term trends were also detected in the longer data run for Agrostis stolonifera, Cirsium arvensa, Poa trivialis, Ranunculus arvensis and Vicia sativa, and for Medicago lupulina on the shorter data run. Variation around long-term trends was low in the case of Equisetum, and, in the longer data run, for Cirsium and Tussilago farfara, and high for Poa spp. and Vicia. Cover values on the two sections were positively correlated for Alopecurus myosuroides, Equisetum, Poa annua and Tripleurospermum inodorum. There was a weak correlation between C-S-R strategy and short-term variability; the more competitive species displayed less variability than the ruderal species. Furthermore, species regenerating from persistent seed banks were more variable in the short term than those regenerating from short-lived seed or bud banks. This can be explained by differences in response to year-to-year variation in environmental conditions, those species with persistent seed banks being typically more sensitive to annual fluctuations in the environment than those without.


Wound infections after colectomy.
The records of 650 patients were analyzed to determine factors predisposing the patients to wound infections. Statistically significant increases in infections were found in association with Crohn's disease, stomas present preoperatively, serum albumin levels of less than 2.9 g/dl, operative blood losses greater than 1,200 ml or operative times longer than two hours, preoperative irradiation, and bowel preparations other than mechanical preparation and nonabsorbable antibiotics. Wound infection did not occur in patients who were prepared for the operation with the neomycin-erythromycin antibiotic regimen.


Internal fixation of fractures of the neck of the femur in hemiplegic patients.
There was a history of hemiplegia due to stroke in 97 (6.5 per cent) of 1483 consecutive patients with fresh fractures of the neck of the femur. Both cervical and trochanteric features occurred significantly more often on the hemiplegic side. Internal fixation was technically satisfactory in trochanteric fractures, but failed frequently in cervical fractures.