Endothelial-like properties of claudin-low breast cancer cells promote tumor vascular permeability and metastasis.
The vasculature serves as the main conduit for breast tumor metastases and is a target of therapeutics in many tumor types. In this study, we aimed to determine if tumor-associated vascular properties could help to explain the differences observed in metastagenicity across the intrinsic subtypes of human breast tumors. Analysis of gene expression signatures from more than 3,000 human breast tumors found that genomic programs that measured vascular quantity, vascular proliferation, and a VEGF/Hypoxia-signature were the most highly expressed in claudin-low and basal-like tumors. The majority of the vascular gene signatures added metastasis-predictive information to immunohistochemistry-defined microvessel density scores and genomically defined-intrinsic subtype classification. Interestingly, pure claudin-low cell lines, and subsets of claudin-low-like cells within established basal-like cancer cell lines, exhibited endothelial/tube-like morphology when cultured on Matrigel. In vivo xenografts found that claudin-low tumors, but not luminal tumors, extensively perfused injected contrast agent through paracellular spaces and non-vascular tumor-lined channels. Taken together, the endothelial-like characteristics of the cancer cells, combined with both the amount and the physiologic state of the vasculature contribute to breast cancer metastatic progression. We hypothesize that the genetic signatures we have identified highlight patients that should respond most favorably to anti-vascular agents.


Novel Parameters to Assess the Severity of Corneal Neovascularization Using Anterior Segment Optical Coherence Tomography Angiography.
Assessment of anterior segment-optical coherence tomography angiography (AS-OCTA) to determine severity of corneal neovascularization (CoNV). Retrospective, cross-sectional, single-center study. Patients of various CoNV etiologies were selected and classified into mild, moderate, and severe. Their AS-OCTA images were measured for CoNV anterior limit, CoNV posterior limit, CoNV thickness, CoNV depth%, CoNV vessel density, CoNV area, and CoNV volume. Further, AS-OCTA parameters were correlated to clinical parameters, such as classification, a numerical severity scale, vascular clock hours, and best-corrected visual acuity (BCVA). A total of 19 mild, 10 moderate, and 6 severe CoNV eyes were included with no significant age-gender differences. CoNV depth% and volume increased from mild to moderate (9.3 ± 1.1% to 17.7 ± 3.3%, P = .030, and 0.2 ± 0.1 mm3 to 1.0 ± 0.3 mm3, P = .025, respectively) and from moderate to severe CoNV (44.6 ± 5.3%, P < .001, and 2.0 ± 0.3 mm3, P = .014, respectively). CoNV area and posterior limit increased from mild to moderate (1.7 ± 0.3 mm2 to 4.6 ± 0.7 mm2, P = .001, and 217.7 ± 16.8 μm to 349.1 ± 54.9 μm, P = .048, respectively), not from moderate to severe (P = .999 and P = .403, respectively). CoNV thickness increased from moderate to severe (218.2 ± 46.6 μm to 340.2 ± 8.7 μm, P = .020), but not from mild to moderate. CoNV area and volume showed good correlations to CoNV staging (r = 0.703 and r = 0.771, respectively; P < .001) and severity scale (r = 0.794 and r = 0.712, respectively; P < .001). CoNV area showed good correlation to clock hours (r = 0.749, P < .001). CoNV depth and volume showed good correlation to BCVA (r = 0.744 and r = 0.722, respectively; P < .001). CoNV anterior limit and vessel density showed no significant correlations (P ≥ .05). Severe CoNV shows greater CoNV posterior limit, thickness, depth%, area, and volume on AS-OCTA compared to mild. CoNV volume and depth strongly correlate to BCVA. AS-OCTA provides novel, quantitative, and noninvasive parameters for assessing CoNV severity.


The effectiveness of activity pacing interventions for people with chronic fatigue syndrome: a systematic review and meta-analysis.
To investigate whether activity pacing interventions (alone or in conjunction with other evidence-based interventions) improve fatigue, physical function, psychological distress, depression, and anxiety in people with chronic fatigue syndrome (CFS). Seven databases were searched until 13 August 2022 for randomised controlled trials that included activity pacing interventions for CFS and a validated measure of fatigue. Secondary outcomes were physical function, psychological distress, depression, and anxiety. Two reviewers independently screened studies by title, abstract and full text. Methodological quality was evaluated using the PEDro scale. Random-effects meta-analyses were performed in R. 6390 articles were screened, with 14 included. Good overall study quality was supported by PEDro scale ratings. Activity pacing interventions were effective (Hedges' g (95% CI)) at reducing fatigue (-0.52 (-0.73 to -0.32)), psychological distress (-0.37 (-0.51 to -0.24)) and depression (-0.29 (-0.49 to -0.09)) and improving physical function (mean difference 7.18 (3.17-11.18)) when compared to no treatment/usual care. The extent of improvement was greater for interventions that encouraged graded escalation of physical activities and cognitive activities. Activity pacing interventions are effective in reducing fatigue and psychological distress and improving physical function in CFS, particularly when people are encouraged to gradually increase activities. PROSPERO CRD42016036087. IMPLICATIONS FOR REHABILITATIONA key feature of chronic fatigue syndrome (CFS) is a prolonged post-exertional exacerbation of symptoms following physical activities or cognitive activities.Activity pacing is a common strategy often embedded in multi-component management programs for CFS.Activity pacing interventions are effective in reducing fatigue and psychological distress and improving physical function in CFS, particularly when patients are encouraged to gradually increase their activities.Healthcare professionals embedding activity pacing as part of treatment should work collaboratively with patients to ensure successful, individualised self-management strategies.


Butyrate mitigates metabolic dysfunctions via the ERα-AMPK pathway in muscle in OVX mice with diet-induced obesity.
The higher prevalence of metabolic syndrome (MetS) in women after menopause is associated with a decrease in circulating 17β-oestradiol. To explore novel treatments for MetS in women with oestrogen deficiency, we studied the effect of exogenous butyrate on diet-induced obesity and metabolic dysfunctions using ovariectomized (OVX) mice as a menopause model. Oral administration of sodium butyrate (NaB) reduced the body fat content and blood lipids, increased whole-body energy expenditure, and improved insulin sensitivity. Additionally, NaB induced oestrogen receptor alpha (ERα) expression, activated the phosphorylation of AMPK and PGC1α, and improved mitochondrial aerobic respiration in cultured skeletal muscle cells. In conclusion, oral NaB improves metabolic parameters in OVX mice with diet-induced obesity. Oral supplementation with NaB might provide a novel therapeutic approach to treating MetS in women with menopause. Video Abstract.


Urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) in tissue and serum of head and neck squamous cell carcinoma patients.
The aim of this study was to determine urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor type 1 (PAI-1) concentrations in tumour and adjacent normal tissue samples from 58 patients, and in serum samples from 40 of 58 patients with squamous cell carcinoma of the head and neck obtained at diagnosis and after completion of therapy. uPA and PAI-1 serum concentrations were also measured in 28 healthy volunteers who served as controls. Measurements were made using enzyme-linked immunosorbent assay (ELISA) techniques. For both uPA and PAI-1, significantly elevated concentrations were measured in tumour tissue as compared with normal tissue (uPA: 8.89 versus 0.41 ng/mg total protein (mgp), P < 0.0001; PAI-1: 23.9 versus 1.47 ng/mgp, P < 0.0001). A statistically significant difference in uPA concentrations was found between normal laryngeal and nonlaryngeal tissue (0.52 versus 0.3 ng/mgp, P = 0.008), and in PAI-1 concentrations between T1 + 2 and T3 + 4 stage of disease (17.32 versus 35.63 ng/mgp, P = 0.04). The uPA concentrations positively correlated with those of PAI-1 measured in both tumour (Rs = 0.62, P < 0.0001) and normal tissue (Rs = 0.30, P = 0.02). In serum samples, lower concentrations of PAI-1 were measured in the control group than in patients with cancer (412.0 versus 680.5 ng/ml serum (mls), P = 0.0006). The time of collection of the serum sample did not influence uPA and PAI-1 concentrations, and no association was observed between their concentrations and any clinical and histopathological prognostic factors tested. Our results indicate that both uPA and PAI-1 may play a specific role in the process of invasion and metastasis, and might also be of prognostic value in squamous cell carcinoma of the head and neck.


Importin beta can mediate the nuclear import of an arginine-rich nuclear localization signal in the absence of importin alpha.
The import of proteins into the nucleus is dependent on cis-acting targeting sequences, nuclear localization signals (NLSs), and members of the nuclear transport receptor (importin-beta-like) superfamily. The most extensively characterized import pathway, often termed the classical pathway, is utilized by many basic-type (lysine-rich) NLSs and requires an additional component, importin alpha, to serve as a bridge between the NLS and the import receptor importin beta. More recently, it has become clear that a variety of proteins enter the nucleus via alternative import receptors and that their NLSs bind directly to those receptors. By using the digitonin-permeabilized cell system for protein import in vitro, we have defined the import pathway for the Rex protein of human T-cell leukemia virus type 1. Interestingly, the arginine-rich NLS of Rex uses importin beta for import but does so by a mechanism that is importin alpha independent. Based on the ability of the Rex NLS to inhibit the import of the lysine-rich NLS of T antigen and of both NLSs to be inhibited by the domain of importin alpha that binds importin beta (the IBB domain), we infer that the Rex NLS interacts with importin beta directly. In addition, and in keeping with other receptor-mediated nuclear import pathways, Rex import is dependent on the integrity of the Ran GTPase cycle. Based on these results, we suggest that importin beta can mediate the nuclear import of arginine-rich NLSs directly, or lysine-rich NLSs through the action of importin alpha.


[Retropharyngeal abscess: case study of 5 cases and literature review].
The purpose of this study was to perform correlation of 5 cases and literature review. The study involved both children and adults. The major cause of retropharyngeal abscess was fish bone foreign body. Dysphagia associated with pain, fever and torticollis were the most common symptoms. Retropharyngeal abscess mainly occurred in the oropharyngeal and hypopharyngeal regions. Imaging tests, in particular CT scan, allowed for accurate information in 3 cases. Aerodigestive tract obstruction was found in most of our patients. Only 4 patients underwent incision and drainage. All patients received medical treatment. A 2-year-old died 5 days after surgery due to septic shock. This study highlights the rarity of this condition in our context as well as the importance of early diagnosis and treatment to prevent life-threatening complications.


Dual energy spectral CT imaging for the evaluation of small hepatocellular carcinoma microvascular invasion.
To study the clinical value of dual-energy spectral CT in the quantitative assessment of microvascular invasion of small hepatocellular carcinoma. This study was approved by our ethics committee. 50 patients with small hepatocellular carcinoma who underwent contrast enhanced spectral CT in arterial phase (AP) and portal venous phase (VP) were enrolled. Tumour CT value and iodine concentration (IC) were measured from spectral CT images. The slope of spectral curve, normalized iodine concentration (NIC, to abdominal aorta) and ratio of IC difference between AP and VP (RICAP-VP: [RICAP-VP=(ICAP-ICVP)/ICAP]) were calculated. Tumours were identified as either with or without microvascular invasion based on pathological results. Measurements were statistically compared using independent samples t test. The receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performance of tumours microvascular invasion assessment. The 70keV images were used to simulate the results of conventional CT scans for comparison. 56 small hepatocellular carcinomas were detected with 37 lesions (Group A) with microvascular invasion and 19 (Group B) without. There were significant differences in IC, NIC and slope in AP and RICAP-VP between Group A (2.48±0.70mg/ml, 0.23±0.05, 3.39±1.01 and 0.28±0.16) and Group B (1.65±0.47mg/ml, 0.15±0.05, 2.22±0.64 and 0.03±0.24) (all p<0.05). Using 0.188 as the threshold for NIC, one could obtain an area-under-curve (AUC) of 0.87 in ROC to differentiate between tumours with and without microvascular invasion. AUC was 0.71 with CT value at 70keV and improved to 0.81 at 40keV. Dual-energy Spectral CT provides additional quantitative parameters than conventional CT to improve the differentiation between small hepatocellular carcinoma with and without microvascular invasion. Quantitative iodine concentration measurement in spectral CT may be used to provide a new method to improve the evaluation for small hepatocellular carcinoma microvascular invasion.


Accreditation: RPVI, RVT, IAC Accreditation, and ACR Accreditation.
Personnel and department accreditation are means by which institutions can evaluate, demonstrate, and maintain the highest level of patient care. In this article, we will discuss the certification and the resources for physicians (RPVI) and technologists (RVT) who provide care to patients in the vascular lab (VL) as well as information about certification by the two accrediting bodies - the Intersocietal Accreditation Commission (IAC) and the American College of Radiology (ACR) - that accredit VLs. Noninvasive vascular testing provides timely delivered valuable information to healthcare providers. Accreditation recognizes quality vascular testing services, but also facilitates a process of education and the quality assurance to improve the overall quality of vascular labs (VL).


Emotional context modulates embodied metaphor comprehension.
Emotions are often expressed metaphorically, and both emotion and metaphor are ways through which abstract meaning can be grounded in language. Here we investigate specifically whether motion-related verbs when used metaphorically are differentially sensitive to a preceding emotional context, as compared to when they are used in a literal manner. Participants read stories that ended with ambiguous action/motion sentences (e.g., he got it), in which the action/motion could be interpreted metaphorically (he understood the idea) or literally (he caught the ball) depending on the preceding story. Orthogonal to the metaphorical manipulation, the stories were high or low in emotional content. The results showed that emotional context modulated the neural response in visual motion areas to the metaphorical interpretation of the sentences, but not to their literal interpretations. In addition, literal interpretations of the target sentences led to stronger activation in the visual motion areas as compared to metaphorical readings of the sentences. We interpret our results as suggesting that emotional context specifically modulates mental simulation during metaphor processing.


Prenatal detection of the congenital nephrotic syndrome (Finnish type) by trehalase assay in amniotic fluid.
We report relatively high trehalase activity in the amniotic fluid of two fetuses affected with the congenital nephrotic syndrome of the Finnish type. The results suggest that prenatal detection of this condition can be done on this basis in conjunction with the alpha-fetoprotein and acetylcholinesterase tests in amniotic fluid.


Dysprosody in Broca's aphasia: a case study.
A detailed acoustic analysis of timing, intensity, and fundamental frequency (F0) at different levels of linguistic structure was conducted on the speech output of a Broca's aphasic who was a native speaker of Thai. Timing was measured with respect to syllables, phrases, and sentences in connected speech. Intensity variation at the sentence level was measured in connected speech. F0 variation associated with the five Thai tones was measured in both isolated words and connected speech. Results indicated that timing was differentially impaired depending upon complexity of articulatory gesture and size of the linguistic structure. Timing, as well as intensity, was aberrant at the sentence level. In contrast, F0 contours of the five tones were spared at all levels of linguistic structure. Findings are interpreted to support the view that dysprosody in Broca's aphasia is more applicable to speech timing than to F0.


Does staff eRostering boost patient outcomes?
The introduction of eRostering to Nottingham University Hospitals Trust highlighted several nursing issues that needed to be addressed but had not previously been fully understood. The eRostering system has given ward managers a better understanding of nursing availability, which has led to improved patient outcomes.


Inhibition of histamine release and phosphatidylcholine metabolism by 5'-deoxy-5'-isobutylthio-3-deazaadenosine.
3-deaza-SIBA, a postulated analogue of S-adenosylhomocysteine, inhibited the IgE-mediated histamine release and blocked both the choline uptake by the rat basophilic leukemia cells and the incorporation of choline into phosphatidylcholine and lysophosphatidylcholine. Unlike inhibitors of methylation which inhibit only dextran- and IgE-mediated reactions, 3-deaza-SIBA also blocked the histamine release from mast cells induced by other secretagogues, such as compound 48/80, ionophore A23187, polymyxin B and ATP. 3-Deaza-SIBA may perturb membrane functions of basophilic leukemia cells and mast cells by inhibiting the biosynthesis of phosphatidylcholine via choline incorporation, the turnover of which is probably required for cellular degranulation and the release of histamine. Previous studies with 3-deaza-SIBA have been mainly interpreted in terms of its structural similarity to S-adenosylhomocysteine and its potential use as an inhibitor of methylation reactions. In light of our present findings, experiments utilizing 3-deaza-SIBA as a biochemical probe have to be carefully interpreted.


New 4-amino-7,8-dimethoxy-5H-pyrimido[5,4-b]indole derivatives: synthesis and studies as inhibitors of phosphodiesterases.
A series of 4-amino-7,8-dimethoxy-5H-pyrimido[5,4-b]indole derivatives has been synthesized. These compounds resemble carbazeram and other pyridazino compounds with activity in the cardiovascular system. Some of these new compounds possess inotropic activity (Table 2), with a complementary effect on the inhibition of different CGI-PDE (Table 3). The most active compounds 5, 6d, and 7 also possess activity as vasodilators (Table 4). Some of these new compounds inhibit blood platelet aggregation induced by ADP and AA and are active as inhibitors of human platelet PDEs (Tables 5 and 6).


Towards automatic waste containers management in cities via computer vision: containers localization and geo-positioning in city maps.
This paper describes the scientific achievements of a collaboration between a research group and the waste management division of a company. While these results might be the basis for several practical or commercial developments, we here focus on a novel scientific contribution: a methodology to automatically generate geo-located waste container maps. It is based on the use of Computer Vision algorithms to detect waste containers and identify their geographic location and dimensions. Algorithms analyze a video sequence and provide an automatic discrimination between images with and without containers. More precisely, two state-of-the-art object detectors based on deep learning techniques have been selected for testing, according to their performance and to their adaptability to an on-board real-time environment: EfficientDet and YOLOv5. Experimental results indicate that the proposed visual model for waste container detection is able to effectively operate with consistent performance disregarding the container type (organic waste, plastic, glass and paper recycling,…) and the city layout, which has been assessed by evaluating it on eleven different Spanish cities that vary in terms of size, climate, urban layout and containers' appearance.


[Levels of emotional awareness in alcohol-dependent patients and abstinent alcoholics].
Deficits in the communication and identifying of feelings are usually observed in addiction disorders. These dysfunctions vary according to the type of addiction and are particularly marked for alcoholic subjects. The prevalence of alexithymia evolves in a nearly linear manner according to the severity and the duration of the disorder. As the duration of alcoholism and the quantity of alcohol that is consumed increase, so will the subjects' scores of alexithymia. In addition, certain authors have observed a decrease in alexithymia in abstinent subjects. Subjects having been abstinent for a long period of time were more alexithymic than those having been abstinent for a shorter period of time. However, other studies failed to confirm these findings and did not observe an increase in the levels of alexithymia in polydrug patients. It seems however that the measures of alexithymia obtained using self evaluation tools (TAS 20) lack in precision due to the fact that, even though the subject is supposed to have a deficit in the identifying and the verbalisation of his emotional states, he is asked to do his own evaluation of the said emotional states. Hence, other tools such as the level of emotional awareness scale (LEAS) offer another approach to the measuring of alexithymia, based on the everyday situations and integrated in a general model of the differentiation of emotional states (or of emotional awareness). The purpose of the study is to describe the level of emotional differentiation of alcoholic subjects, and to evaluate the development of the emotional processes following alcohol cessation. Our sample consists of 88 subjects distributed in three groups: a group of alcoholic participants who are in the process of quitting alcohol (33 subjects), a group of alcoholic participants that have been abstinent for more than 6 months (20 subjects) and a group of control participants (35 subjects). The prevalence of alexithymia is estimated by the Toronto alexithymia scale (TAS 20) which measures three factors: the difficulty to identify one's feelings (TAS 1), the difficulty to express one's feelings (TAS 2), and thoughts which are directed towards the outside world (TAS 3). The levels of emotional consciousness are estimated by the LEAS which establishes 20 scenarios in order to measure three scores: emotional consciousness "for oneself" (LEAS 1), emotional consciousness "for others" (LEAS 2) and a total score (total LEAS). The results show a different level of emotional awareness and alexithymia between the three groups of participants. The alcoholic participants are less conscious of their feelings and have more difficulties identifying and expressing their feelings than the control subjects. With regards to the evolution of the emotional deficit linked to alcohol withdrawal, the abstinent subjects obtain weaker scores of alexithymia than the alcoholic subjects. However, abstinent subjects continue to present more difficulties expressing their feelings than control subjects (TAS 2). On the other hand, abstinent subjects' levels of emotional awareness are once again comparable to those of control subjects. Finally, the analysis of the correlations does not show any link between the scores of alexithymia and the scores of emotional consciousness, and this for all of the groups studied. Our major result concerns the recovery of the emotional deficit of abstinent subjects (global score of TAS 20 and the score of emotional consciousness), which underlines the importance of the implementation of therapeutic protocols that focus on the emotional awareness of alcoholic subjects.


Usefulness of echocardiographic myocardial work in evaluating the microvascular perfusion in STEMI patients after revascularization.
Left ventricular myocardial work (MW) assessed by echocardiography has recently been introduced as a new index of global and regional myocardial performance. The presence of microvascular obstruction after revascularization in ST-segment elevation myocardial infarction (STEMI) patients predicts poor clinical outcomes. This study aimed to explore the usefulness of MW in identifying impaired microvascular perfusion (MVP) in the patients with STEMI after revascularization. One hundred and sixty STEMI patients who underwent myocardial contrast echocardiography (MCE) within 48 h after percutaneous coronary intervention (PCI) were included. Patients were divided into normal MVP and impaired MVP groups according to the myocardial perfusion score. The clinical data, coronary angiography results and echocardiographic data including Global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE) were collected. Impaired MVP was found in 60% of patients. Compared with the normal MVP group, GWI (909.2 ± 287.6 mmHg% vs. 1191.2 ± 378.2 mmHg%), GCW (1198.3 ± 339.6 mmHg% vs. 1525.9 ± 420.5 mmHg%), GWE (82.7 ± 7.8% vs. 86.8 ± 5.6%) and GLS (- 11.0 ± 3.4% vs. - 14.4 ± 3.8%) were significantly reduced in the impaired MVP group. Whereas there was no statistically significant difference in left ventricular ejection fraction (LVEF) and GWW, multivariate logistic regression analysis showed that peak troponin I (OR 1.017, 95% CI 1.006-1.029; P = 0.004), final TIMI flow ≤ 2 (OR 16.366, 95% CI 1.998-134.06; P = 0.009), left ventricular end-diastolic volume index (LVEDVi) (OR 1.139 95% CI 1.048-1.239; P = 0.002), and GWI (OR 0.997 95% CI 0.994-1.000; P = 0.029) were independently associated with impaired MVP. GWI showed a good sensitivity (86.8%) but low specificity (53.7%) in identifying impaired MVP (AUC 0.712, 95% CI 0.620-0.804; P < 0.001). Combination with GWI can improve the diagnostic value of TNI or LVEVi for impaired MVP. Impaired MVP is relatively common in STEMI patients after revascularization and independently associated with left ventricular GWI assessed by echocardiography. GWI confer incremental value to MVP assessment in STEMI patients.


Allosteric regulation of thioesterase superfamily member 1 by lipid sensor domain binding fatty acids and lysophosphatidylcholine.
Nonshivering thermogenesis occurs in brown adipose tissue to generate heat in response to cold ambient temperatures. Thioesterase superfamily member 1 (Them1) is transcriptionally up-regulated in brown adipose tissue upon exposure to the cold and suppresses thermogenesis in order to conserve energy reserves. It hydrolyzes long-chain fatty acyl-CoAs that are derived from lipid droplets, preventing their use as fuel for thermogenesis. In addition to its enzymatic domains, Them1 contains a C-terminal StAR-related lipid transfer (START) domain with unknown ligand or function. By complementary biophysical approaches, we show that the START domain binds to long-chain fatty acids, products of Them1's enzymatic reaction, as well as lysophosphatidylcholine (LPC), lipids shown to activate thermogenesis in brown adipocytes. Certain fatty acids stabilize the START domain and allosterically enhance Them1 catalysis of acyl-CoA, whereas 18:1 LPC destabilizes and inhibits activity, which we verify in cell culture. Additionally, we demonstrate that the START domain functions to localize Them1 near lipid droplets. These findings define the role of the START domain as a lipid sensor that allosterically regulates Them1 activity and spatially localizes it in proximity to the lipid droplet.


Fermented Yupingfeng polysaccharides enhance immunity by improving the foregut microflora and intestinal barrier in weaning rex rabbits.
Yupingfeng (YPF) is a kind of Astragali radix-based ancient Chinese herbal supplemented with Atractylodis Macrocephalae Rhizoma and Radix Saposhnikoviae. Increasing evidence has proven the beneficial immunomodulating activity of YPF. However, the action mechanism(s) of it is not known. Here, we explored the immunomodulatory activity of unfermented Yupingfeng polysaccharides (UYP) and fermented Yupingfeng polysaccharides (FYP) obtained using Rhizopus oligosporus SH in weaning Rex rabbits. The results showed that both UYP and FYP exhibited notable growth-promoting and immune-enhancing activities, improvement of the intestinal flora homeostasis, and maintenance of intestinal barrier integrity and functionality. Notably, compared with UYP, FYP effectively enhanced average daily gain, organ indices, interleukin-2 (IL-2), IL-4, IL-10, tumor necrosis factor-alpha (TNF-α), TLR2, and TLR4 mRNA levels in spleen, IL-1, IL-2, IL-4, IL-6, IL-10, IL-12, TNF-α, and IFN-γ protein concentrations in serum, and TLR2 and TLR4 mRNA expressions in the gastrointestinal tract (GIT). Moreover, FYP exhibited greater beneficial effects in improving the intestinal flora, including augment flora diversity and the abundance of cellulolytic bacteria, reduction the abundance of Streptococcus spp. and Enterococcus spp. in the GIT, particularly the foregut and maintaining the intestinal barrier integrity and functionality by upregulating zonula occludens 1, claudin, polymeric immunoglobulin receptor, trefoil factor, and epidermal growth factor mRNA levels in the jejunum and ileum. Our results indicated the immunoenhancement effect of FYP is superior over that of UYP, which is probably related with the amelioration of the intestinal microflora and intestinal barrier in the foregut.


Modified Limberg's transposition flap for pilonidal sinus. Long term follow up of 216 cases.
to report our results in a large series of patients with chronic pilonidal sinus (PS) at long term follow up. Two hundred sixteen patients underwent excision and rhomboid flap transposition (RFT) from 1986 to 2004 for PS, and followed for more than two years. Clinical presentation includes: pilonidal abscess treated by drainage (33%), chronic discharge (48%) and simple infected sinus (19%). Mean follow-up was 74.4 months (range: 24-96). Minimal flap necrosis occurred in 5 pts (2.3%), post operative infection in 2 pts (0.9%), 4 pts (1.8%) had a seroma, 18 pts (8.3%) anesthesia or hypoesthesia on the upper portion of the flap. The mean hospitalization was 3.1 +/- 0.30 days and return to work was 10.8 +/- 2.4 days. Recurrences occurred in 5 pts (7.4%) in our initial 87 pts. Since we modified the technique no recurrences were seen. The Limberg's technique is a very effective procedure for chronic or recurrent PS with a low complications rate, a short hospital stay, a rapid return to normal activities and a low recurrence rate. Moreover with the modified technique the wound healing and the rate of recurrences have shown a significant decrease.


Extraction optimization and characterization of pectin from sesame (Sesamum indicum L.) capsule as a new neglected by-product.
With production of over 6 million tonnes a year of sesame, its capsules are considered to be an unutilized waste. In this study, extraction of pectin from this novel source was optimized using a green method, and the functional and physiochemical characteristics of the resultant pectin were compared to commercial pectin. In this study, the sesame capsule pectin (SCP) extraction conditions were optimized to reach maximum yield, and the results showed that the maximum pectin extraction yield (138 g kg-1 ) was obtained under optimal conditions (microwave power 700 W, irradiation time 5 min, pH 1.5, and liquid-to-solid ratio 41.8 (mL g-1 ). The results showed that the pectin was low methoxyl type with a galacturonic acid content of 670 g kg-1 . The extracted pectin had a high molecular weight (341 kDa) and surface charge (34.09 ± 1.88 mV) and exhibited 66% DPPH radical scavenging. The obtained results from 1 H-nuclear magnetic resonance and Fourier transform infrared spectra validated the presence of pectin structure in the extracted sample. Sesame capsule pectin, when compared to commercial pectin, demonstrated better functional properties in terms of emulsifying properties, oil holding capacity, foaming capacity and antioxidant activity. SCP showed similar properties in comparison to its commercial counterpart, which suggests that it could well be considered as a new and suitable source for pectin extraction. © 2022 Society of Chemical Industry.


Pathogenesis of adenocarcinoma complicating ureterosigmoidostomy. Experimental observations.
Columnar metaplasia, dysplasia, and adenocarcinoma occurred in patches of bladder epithelium exposed to the fecal stream in rats. This suggests that such tumors complicating ureterosigmoidostomy may arise from ureteric epithelium, and that urine is not essential for their development.


Consecutive reaction kinetics involving a layered structure of the granule in UASB reactors.
A consecutive-reaction kinetic model for the sucrose-fed upflow anaerobic sludge bed (UASB) reactor that accounts for a layered structure of the granule and the mass fraction of methanogens (f) is proposed. When the UASB reactor was maintained at the volumetric loading rates (VLR) of 7.9-13.8 kg chemical oxygen demand (COD)/m(3) d, the accumulated volatile fatty acids (VFAs) increased with increasing VLR, whereas the experimental f decreased with increasing VLR. This was primarily because methanogenesis was the rate-limiting step and the sucrose-fed granule was a layered structure. The calculated residual concentrations of sucrose and the intermediates VFAs using the layered-structure model are less deviated from the experimental measurements than those using the homogeneous-structure model. The calculated effectiveness factors for sucrose uptake and intermediates VFAs uptake (eta(1); eta(2)) ranged from 0.18 to 0.35 and 0.65 to 0.96, respectively, indicating that the overall substrate (sucrose or intermediates VFAs) removal in the UASB reactor was diffusion-controlled, especially at the VLRs of 7.9-10.6. kg COD/m(3) d. This finding was also confirmed by the simulated concentration profiles of sucrose and VFAs in the UASB-granule. From the simulation results, the effect of internal mass transfer resistance on overall substrate (sucrose) removal should not be neglected, especially for a granule size of greater than 2.0 mm.


Imaged thoracic lobectomy: should it be done?
Imaged thoracic surgery is a new modality that is rapidly gaining acceptance from thoracic surgeons. Procedures that traditionally required a thoracotomy can now be done successfully using this technique in some patients. Three patients with primary carcinoma of the lung have undergone lobectomy using imaged thoracic surgery.


Mycotoxin production by some IndianAlternaria species.
A total of seven species ofAlternaria: A. alternata (Fr.) Keissler;A. capsici-annui Savul & Sandu;A. citri Ellis & Pierce;A. porri (Ellis) Clfferi;A. radicina Meler, Drechsler & Eddy;A. tenuissima (Kunze: Pers) Wiltshire andA. tomato (Cooke) Jones were screened on rice culture medium for their ability to elaborate five majorAlternaria mycotoxins viz. tenuazonlc acid (TA), alternariol (AOH), alternariol methyl ether (AME), altenuene (ALT) and altertoxin-l (ATX-I). All the species produced mycotoxins in varying concentrations. A.capsici-annul was recorded as the mycotoxin producer for the first time. ALT byA. citri andA. tomato; ALT, and ATX-I byA. tenuissima; ALT, TA and AME byA. porri and TA byA. radicina are the new additions to the list of mycotoxins produced by the respective species ofAlternaria.


Sagittal skin contour of the cervical spine: interexaminer and intraexaminer reliability of the flexicurve instrument.
To evaluate reliability of a simple instrument, the flexicurve, in determining cervical sagittal skin contour. This study obtained repeated random measurements involving 3 investigators and 30 subjects once per day over a 2-day trial period. Thirty normal subjects were examined for cervical spine skin contour twice by 3 separate investigators with a 1-day delay. With subjects in a neutral standing position, investigators placed the flexicurve on the posterior portion of the subject's neck from the external occipital protuberance to the vertebral prominens and traced the flexicurve shape onto paper. The tracings were divided into 6 equal arcs and digitized. Statistical computation was performed on the depth at 5 points, arc angle, and arc radius of curvature. Interexaminer and intraexaminer correlation coefficients (ICCs) were calculated to determine reliability. All interexaminer correlation coefficients were in the poor range (<0.40). For the arc radius, arc angle, depth at top one third, and depth at bottom two thirds, the intraexaminer correlation coefficients were in the poor range. For the 3 deepest depths, the intraexaminer correlation coefficients were in the fair range (0.4-0.50). The flexicurve showed marginal reliability with most (12/16) ICCs in the poor range (ICC <0.40) and 4 values in the fair range (0.4 < ICC < 0.5).


Spontaneous Extrusion of Ventriculoperitoneal Shunt Catheter through the Right Lumbar Region: A Case Report and Review of the Literature.
Ventriculoperitoneal shunt surgery is the most frequently performed procedure in the management of hydrocephalus. Many varied complications related to this procedure have been reported. Distal migration of the peritoneal catheter and extrusion from the intact skin in an area unrelated to the surgical incision constitute a rare complication. We report a 1-year-old patient with the extrusion of the peritoneal catheter from the intact skin in the right lumbar region and present a literature review.


Device-related complications of long-term intrathecal drug therapy via implanted pumps.
Case series. To evaluate the risk of pump- and catheter-related complications of intrathecal drug delivery systems. Tertiary care center in Switzerland. The medical records of all in- and out-patient adults treated at our institution during a 12-year period were reviewed. All patients that had received intrathecal drug therapy via an implanted pump were invited to a structured interview. One hundred patients, representing therapy with 175 implanted pumps and 132 intrathecal catheters over 552 years, participated in the study. During the observation period, 217 surgical procedures (including 100 primary pump implants) and 5863 pump refills were performed. The annual rate for complications requiring surgical measures was 10.5%, with 35% being pump related and 65% being catheter related. The incidence of infections in our patients was 0.7% per year; all infections appeared during the first 3 months after implantation of the first pump. Complication rates of the patients treated in our center, where we have long-term experience with the indication, implantation and continuous care of patients with intrathecal infusion systems, are in the lowest ranges when compared with other published studies. We consider intrathecal testing before implantation, standardized perioperative procedures and consequent long-term care of the patients in a specialized outpatient clinic to be essential factors for the avoidance of complications.


A proteomic analysis of cold stress responses in rice seedlings.
Using proteomic analysis, an investigation aimed at a better understanding of the molecular adaptation mechanisms of cold stress was carried out in rice (Oryza sativa). The seedlings were exposed to a progressively low temperature stress treatment from normal temperature to 15, 10, and 5 degrees C. Proteins were extracted from the leaves collected from both control and stressed seedlings. By fractionation, approximately 1700 protein spots were separated and visualized on CBB-stained 2-D gels. Sixty protein spots were found to be up-regulated in responding to the progressively low temperature stress and displayed different dynamic patterns. As an initial work, 41 of these proteins were identified using MALDI-TOF MS or ESI/MS/MS. These cold responsive proteins, besides two proteins of unknown function, include four factors of protein biosynthesis, four molecular chaperones, two proteases, and eight enzymes involved in biosynthesis of cell wall components, seven antioxidative/detoxifying enzymes, and proteins linked to energy pathway, as well as a protein involved in signal transduction. The functional proteomes illuminate the facts, at least in plant cell, that protein quality control mediated by chaperones and proteases and enhancement of cell wall components play important roles in tolerance to cold stress. Using TargetP program, the subcellular localization of the identified proteins was analyzed. Proteins (43.9%) were predicted to be located in the chloroplasts, implying that chloroplast proteome is virtually subjective to cold stress. The physiological implications, revealed from the experimental data, are discussed in context of a complex metabolic network in plant cells responsive to cold stress.


Freezing-enhanced oxidation of iodide by hydrogen peroxide in the presence of antifreeze proteins from the Arctic yeast Leucosporidium sp.AY30.
Ice-binding proteins (IBPs), originating from Arctic or Antarctic microorganisms, have freeze-inhibiting characteristics, allowing these organisms to survive in polar regions. Despite their significance in polar environments, the mechanism through which IBPs affect the chemical reactions in ice by controlling ice crystal formation has not yet been reported. In this study, a new mechanism for iodide (I-) activation into triiodide (I3-), which is the abundant iodine species in seawater, by using hydrogen peroxide (H2O2) in a frozen solution with IBPs was developed. A significant enhancement of I- activation into I3- was observed in the presence of Arctic-yeast-originating extracellular ice-binding glycoprotein (LeIBP) isolated from Leucosporidium sp. AY30, and a further increase in the I3- concentration was observed with the introduction of H2O2 to the frozen solution (25 times higher than in the aqueous solution after 24 h of reaction). The reaction in the ice increased with an increase in LeIBP concentration. The in-situ pH measurement in ice using cresol red (CR) revealed protons accumulated in the ice grain boundaries by LeIBP. However, the presence of LeIBP did not influence the acidity of the ice. The enhanced freeze concentration effect of H2O2 by LeIBP indicated that larger ice granules were formed in the presence of LeIBP. The results suggest that LeIBP affects the formation and morphology of ice granules, which reduces the total volume of ice boundaries throughout the ice. This leads to an increased local concentration of I- and H2O2 within the ice grain boundaries. IBP-assisted production of gaseous iodine in a frozen environment provides a previously unrecognized formation mechanism of active iodine species in the polar regions.


Multi-decadal ocean temperature time-series and climatologies from Australia's long-term National Reference Stations.
Multi-decadal ocean time-series are fundamental baselines for assessing the impacts of environmental change, however, compiling and quality controlling historic data from multiple sources remains challenging. Here we aggregate, document, and release a number of long time-series temperature products and climatologies compiled from data obtained at 4 monitoring sites around Australia where sub-surface ocean temperature has been recorded nominally weekly to monthly since the 1940s/50s. In recent years, the sampling was augmented with data obtained from moored sensors, vertical profiles and satellite-derived data. The temperature data have been quality controlled, and combined using a rigorously tested methodology. We have packaged the multi-decadal, multi-depth, multi-platform temperature time-series at each site and produced a range of daily temperature climatologies from different data combinations and time periods. The 17 data products are provided as CF-compliant NetCDF files and will be updated periodically. The long-term temperature time-series will be useful for studies of ocean temperature variability, trends, anomalies and change. The data collection is supported by Australia's Integrated Marine Observing System and data are open-access.


Signalling pathways for cardiac hypertrophy.
Mechanical stretch is an initial factor for cardiac hypertrophy in response to haemodynamic overload (high blood pressure). Stretch of cardiomyocytes activates second messengers such as phosphatidylinositol, protein kinase C, Raf-1 kinase and extracellular signal-regulated protein kinases (ERKs), which are involved in increased protein synthesis. The cardiac renin-angiotensin system is linked to the formation of pressure-overload hypertrophy. Angiotensin II increases the growth of cardiomyocytes by an autocrine mechanism. Angiotensin II-evoked signal transduction pathways differ among cell types. In cardiac fibroblasts, angiotensin II activates ERKs through a pathway including the Gbetagamma subunit of Gi protein, Src family tyrosine kinases, Shc, Grb2 and Ras, whereas Gq and protein kinase C are important in cardiac myocytes. In addition, mechanical stretch enhances the endothelin-1 release from the cardiomyocytes. Further, the Na+ -H+ exchanger mediates mechanical stretch-induced Raf-1 kinase and ERK activation followed by increased protein synthesis in cardiomyocytes. Not only mechanical stress, but also neurohumoral factors induce cardiac hypertrophy. The activation of protein kinase cascades by norepinephrine is induced by protein kinase A through beta-adrenoceptors as well as by protein kinase C through alpha-adrenoceptors.


Pollution-related changes in diets of two insectivorous passerines.
Insectivorous birds living in polluted areas are not only exposed to pollutants but they may also be affected by changes in their invertebrate food. The populations of many invertebrate species are affected by environmental pollution and such changes may lead to differences in the diet of insectivorous birds. We examined nestling food quality (invertebrate composition and heavy metal levels) and breeding performance of two cavity-nesting passerines, the Great tit, Parus major, and the pied flycatcher, Ficedula hypoleuca, in an area with long-term heavy metal pollution by a copper smelter. There were no differences in feeding frequencies or the amount of food that parents provided to their nestlings between polluted and unpolluted sites, but food quality in a polluted area differed from that of the control area in both bird species. P. major took more beetles and variable "flying insects" and less caterpillars (of smaller size) and moths in the polluted area as compared to the unpolluted one. F. hypoleuca ate more beetles and larvae and less moths and spiders in the polluted area. Breeding success of P. major was better when the nestling diet contained a large proportion of caterpillars and the relationship was especially strong in the polluted area. On the contrary, F. hypoleuca broods succeeded equally well with variable diets. Our data suggest that a more opportunistic forager, F. hypoleuca, is less vulnerable to a changing invertebrate composition caused by human environmental impacts than a caterpillar specialist, P. major. In a heavy metal polluted area, F. hypoleuca seems to be more sensitive to a decreased amount of Ca rich food items (e.g. snails) while P. major suffers especially from the lack of carotenoid rich caterpillars. Our results emphasize the importance of secondary environmental changes, like food quality, in addition to direct impacts of pollutants.


Effects of a challenge dose of Salmonella Typhimurium or Salmonella Yoruba on the patterns of excretion and antibody responses of pigs.
The epidemiology of a feed-associated Salmonella serotype (Salmonella Yoruba) was compared with that of a 'classical' serotype (Salmonella Typhimurium) by inoculating pigs aged 10 weeks with 0.65 x 10(3), 0.65 x 10(6) or 0.65 x 10(9) colony-forming units (cfu) of either serotype. The pigs were then monitored for eight weeks with respect to the faecal excretion of Salmonella species and the presence of serum antibodies. Only minor differences were observed between the two serotypes but the dose inoculated had significant effects. The pigs inoculated with 0.65 x 10(9) cfu shed Salmonella species in faeces constantly for four weeks, and intermittently during the subsequent four weeks; the pigs inoculated with 0.65 x 10(6) cfu shed Salmonella species intermittently for four weeks, but not for longer, and the pigs inoculated with 0.65 x 10(3) cfu generally did not excrete Salmonella species. The pigs inoculated with 0.65 x 10(9) cfu S Typhimurium seroconverted at a high titre within two weeks, the pigs inoculated with 0.65 x 10(6) cfu seroconverted later and with lower titres of antibodies, and the pigs inoculated with 0.65 x 10(3) cfu did not seroconvert. A similar pattern was observed with S Yoruba, but the responses were slower and at lower titres.


The Short-Term Outcomes of Gastric Cancer Patients Based on a Proposal for a Novel Classification of Perigastric Arteries.
To establish a novel classification of perigastric arteries by computerized tomography angiography (CTA) and discuss its influence in patients' short-term clinical outcomes. The clinical data were analyzed retrospectively from 680 gastric cancer patients. The types of the perigastric artery were classified according to CTA image and we compared the short-term clinical outcomes. The perigastric arteries can be divided into seven categories. Type I, trifurcation of the celiac trunk (CT) (294/343, 85.7%); type II, hepatosplenic trunk, left gastric artery (LGA) arising from the abdominal aorta (8/343, 2.3%); type III, hepatogastric trunk, splenic artery arising from the superior mesenteric artery (SMA) (2/343, 0.6%); type IV, celiacomesenteric trunk (5/343, 1.5%); type V, common hepatic artery (CHA) arising from the SMA, gastrosplenic trunk (11/343, 3.2%); type VI, aberrant (accessory or replaced) left hepatic artery arising from LGA (21/343, 6.1%); and type VII, CHA arising from LGA (2/343, 0.6%). The number of retrieved LNs in the CTA group was significantly higher than that in the non-CTA group. However, the operation time, estimated blood loss, intraoperative vascular injury, and medical cost of the CTA group were significantly less than those in the non-CTA group. Of note, in patients with BMI ≥ 25.0, higher LNs retrieval and less vascular injury were still present in the CTA group, which was of vital importance in clinical practice. Furthermore, the CTA group displayed shorter hospital stay (LOS). We established a new perigastric artery classification. Application of the classification can improve the short-term clinical outcomes of patients.


Cockcroft-Gault versus modification of diet in renal disease: importance of glomerular filtration rate formula for classification of chronic kidney disease in patients with non-ST-segment elevation acute coronary syndromes.
Our purpose was to compare formulae for estimating glomerular filtration rate (GFR) in non-ST-segment elevation acute coronary syndromes (NSTE ACS) patients. Assessment of GFR is important for antithrombotic dose adjustment in NSTE ACS patients. We assessed estimated glomerular filtration rate (eGFR) with Cockcroft-Gault (C-G) and Modification of Diet in Renal Disease (MDRD) formulae in 46,942 NSTE ACS patients from 408 CRUSADE (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the American College of Cardiology/American Heart Association Guidelines) hospitals. Formula agreement was shown continuously and by chronic kidney disease (CKD) stages. We determined in-hospital outcomes and the association between antithrombotic dose adjustment and bleeding for moderate CKD as determined by each formula. The median (interquartile range [IQR]) eGFR was 53.2 ml/min (34.7, 75.1 ml/min) by C-G and 65.8 ml/min (47.6, 83.5 ml/min) by MDRD. The mean eGFR was higher with MDRD (approximately 9.1 ml/min), but this difference was greater in age, weight, and gender subgroups. Chronic kidney disease classification differed in 20% of the population and altered when antithrombotic dose adjustment was required by C-G versus MDRD (eptifibatide: 45.7% vs. 27.3%; enoxaparin: 19.0% vs. 9.6%). Important CKD disagreements occur in approximately 20% of acute coronary syndrome patients, affecting dosing adjustments in those already susceptible to bleeding. Dosing based on C-G formula is preferable, particularly in the small, female, or elderly patient.


Tracheal intubation after induction of anaesthesia with propofol, alfentanil and lidocaine without neuromuscular blocking drugs in children.
In a double-blind study, intubating conditions and haemodynamic responses were assessed in two age-groups of 45 ASA I-II children, with mean ages of 2.4 and 6.3 years, premedicated with oral midazolam and atropine. The children were randomly allocated to one of three groups: alfentanil 20 micrograms.kg-1 + lidocaine 1 mg.kg-1 (Alf20 + Lign); alfentanil 20 micrograms.kg-1 (Alf20); or alfentanil 40 micrograms.kg-1 (Alf40), followed by propofol 3.5 mg.kg-1 in the children aged 1-3 years and 3.0 mg.kg-1 in the older children. Intubating conditions, 40 s after the administration of propofol, were assessed as good, moderate or impossible on the basis of jaw relaxation, ease of insertion of the endotracheal tube and coughing during intubation. In the younger age group the frequencies of good, moderate or impossible intubating conditions were 87, 13 and 0% in the Alf40, 40, 60 and 0% in the Alf20 (P < 0.05 compared to the Alf40 group) and 53, 47 and 0% in the Alf20 + Lign group. In the older age group the corresponding frequencies were 60, 33 and 7% in the Alf20 + Lign, 47, 53 and 0% in the Alf20 and 47, 40 and 13% in the Alf40 group. All the drugs prevented any increase in arterial pressure and heart rate after tracheal intubation. The QTc interval of the ECG was always in the normal range. Clinically important bradycardia did not occur. In conclusion, the best intubating conditions occurred after propofol 3.5 mg.kg-1 and alfentanil 40 micrograms.kg-1 in the younger age group.(ABSTRACT TRUNCATED AT 250 WORDS)


Multifunctional Layer-by-Layer Coating Based on a New Amphiphilic Block Copolymer via RAFT-Mediated Polymerization-Induced Self-Assembly Process.
In this hi-tech world, the "smart coatings" have sparked significant attention among materials scientists because of their versatile applications. Various strategies have been developed to generate smart coatings in the past 2 decades. The layer-by-layer (LbL) technique is the most commonly employed strategy to produce a smart coating for suitable applications. Here, we present a smart coating with healing, antifogging, and fluorescence properties fabricated by the LbL assembly of an anionic amphiphilic block copolymer latex and cationic inorganic POSS (polyhedral-oligomeric-silsesquioxane) nanoparticles. In this case, a new anionic block copolymer (BCP), {poly(sodium styrene sulfonate)-block-poly[2-(acetoacetoxy)ethyl methacrylate]}, (PSS-b-PAAEMA) was synthesized via surfactant-free RAFT-mediated emulsion polymerization using the PISA technique. The PSS-b-PAAEMA was characterized by 1H NMR, dynamic light scattering, scanning electron microscopy, and transmission electron microscopy analyses as well as by UV-vis and photoluminescence spectroscopy. For LbL coating fabrication, an amine-modified glass was successively dipped in the anionic latex and cationic POSS solution. The transparent coating exhibited good fluorescence properties under UV light (blue color). The antifogging performance of the coating was also investigated using both cold-warm and hot-vapor techniques. Additionally, the coating surface showed a significant healing activity with a healing efficiency of >75% through ionic interaction. Thus, this finding provides a simple low volatile organic compound (VOC) water-based LbL coating with multifunctional properties that can be a potential material for versatile applications.


The frequency of vesicoureteral reflux diagnosis is correlated with urbanization level of residence in pediatric population: a nationwide study in Taiwan.
To investigate the frequency and characteristics of newly diagnosed vesicoureteral reflux (VUR) in children younger than 18 years based on a nationwide database in Taiwan. The present study utilizes a subset of the Taiwan's National Health Insurance Research Database, known as the Longitudinal Health Insurance Database 2005, which contains the data of all paid medical benefit claims over 1997-2007 for a subset of 1,000,000 beneficiaries randomly drawn from the population of 22.72 million individuals during any part of the 2005 calendar year. Our analysis includes the data of all pediatric patients with the diagnosis of VUR. A total of 738 subjects with VUR diagnosis were identified, including 412 (55.8%) boys and 326 (44.2%) girls. The peak age of VUR occurrence was the first year for males and 1-4 years for females. Approximately 49.7% of all subjects presented with urinary tract infection (UTI); moreover, there were significant differences between genders concerning the presence of UTI (RR = 0.8; p = 0.002). The occurrence rate of VUR in the pediatric population ranged from 2.63 in 1998 to 3.94 in 2003 per 10,000 children during 1998-2005. The frequency of newly-diagnosed VUR in the pediatric population was significantly correlated with urbanization levels of residence. The nationwide, population-based study of pediatric VUR shows there were gender differences in age distribution and presence of UTI. Further studies are warranted to clarify the correlations between urbanization level of residence and occurrence of VUR.


A case of dens fracture: a pictorial review and discussion.
Dens fractures are more common in the elderly and may present after minimal trauma and with minimal neck pain. The case reports a case of a significant fracture after minimal trauma, presenting with neurologic symptoms and minimal neck pain.


P63 expression in hydropic abortion and gestational trophoblastic diseases.
Gestational trophoblastic diseases are a group of interrelated diseases of trophoblastic tissue that include partial hydatidiform mole, complete hydatidiform mole, invasive mole, choriocarcinoma, and placental site trophoblastic tumor. P63 is a p53 homologue that, in normal placentas, is expressed in the cytotrophoblast cells. The role of p63 in gestational trophoblastic diseases, however, merits further investigation. Immunohistochemistry with the p63 antibody (clone 4A4) was performed in formalin-fixed paraffin-embedded samples of hydropic abortion (n=10), partial hydatidiform mole (n=12), complete hydatidiform mole (n=12) and choriocarcinoma (n=5). P63 expression was quantitatively assessed as 0 (no stained cells), + (less than 10% positive cells), ++ (10-50% positive cells), and +++ (more than 50% positive cells). The intensity was scored as 0 (absence), + (weak), ++ (moderate), or +++ (strong). Statistical analysis was carried out by the Fisher test. In contrast to the other diagnoses, none of the choriocarcinomas analyzed exhibited p63-positive cells. There was no difference in distribution of p63 positive cells between hydropic abortion, partial hydatidiform mole, and complete hydatidiform mole. Concerning the intensity of immunostaining, there was difference only between partial hydatidiform mole and complete hydatidiform mole. According to our results, p63 might be useful to differentiate a choriocarcinoma from other gestational trophoblastic diseases. Besides, since the intensity of p63 expression was much stronger in partial hydatidiform mole and complete hydatidiform mole than in hydropic abortion, this feature may be helpful in distinguishing these two diagnoses in challenging cases.


Orbital masses: CT and MRI of common vascular lesions, benign tumors, and malignancies.
A wide variety of space occupying lesions may be encountered in the orbit. CT and MR imaging frequently help confirm the presence of a mass and define its extent. Characteristic imaging features may help distinguish among lesions that have overlapping clinical presentations. This review focuses on some of the common orbital masses. Common vascular lesions that are reviewed include: capillary (infantile) hemangioma, cavernous hemangioma (solitary encapsulated venous-lymphatic malformation), and lymphangioma (venous-lymphatic malformation). Benign tumors that are reviewed include: optic nerve sheath meningioma, schwannoma, and neurofibroma. Malignancies that are reviewed include: lymphoma, metastasis, rhabdomyosarcoma, and optic glioma. Key imaging features that guide radiological diagnosis are discussed and illustrated.


Alternative treatment for asthma: case study of success of traditional chinese medicine treatment of children from urban areas with different levels of environmental pollution.
The present study examined efficacy of traditional Chinese medicine (TCM) treatment in Dutch children with asthma in areas with differing air pollution. The study results indicate that TCM treatment of children living in more polluted urban area is less successful then that of children living in cleaner air area.


Hepatitis C infection in children: a Melbourne perspective.
To examine the clinical spectrum of hepatitis C virus (HCV) infected children in our care by determining presentation, mode of acquisition, degree of co-infection, biochemical evidence of persisting hepatitis and treatment outcome. A retrospective review of the medical records of all children attending the Royal Children's Hospital, Melbourne, between 1990 and 1998, who had antibodies to HCV infection detected. Detailed clinical information, investigations and the results of treatment were extracted from the clinical notes. A total of 94 children (age range 2 weeks to 19.7 years) were identified, of whom nine had passive transfer of maternal antibodies from HCV-positive mothers and were excluded from analysis. Sixty-seven children (79%) were infected by transfusion of blood or blood products. Perinatal transmission occurred in 11 children (13%), and six children (7%) had a history of i.v. drug abuse. The majority of children were asymptomatic at presentation. Of the 65 patients tested for HCV-ribonucleic acid, 43 (66%) were positive. Fifty-seven cases had serial alanine aminotransaminase (ALT) measurements over a mean of 28 months. Of these, 38 (67%) had an abnormal ALT. Ten cases (12%) were co-infected with hepatitis B virus, HIV or both. Of 12 patients treated with interferon, four responded with normalisation of ALT from 3 to 12 months post-commencement of therapy. Although HCV was largely an asymptomatic condition in our clinic population, more than half the patients had biochemical evidence of ongoing liver damage. Given the chronicity of this infection in the majority of patients and the long-term risks of cirrhosis and hepatocellular carcinoma, children with HCV infection represent a high-risk group worthy of regular follow up.


The GPEP report on undergraduate medical education. Implications for rehabilitation medicine. Association of American Medical Colleges, panel on the General Professional Education of the Physician.
The Association of American Medical College's project panel on the General Professional Education of the Physician (GPEP) and College Preparation for Medicine and its working groups appear to share many values with professionals involved in rehabilitation medicine. The GPEP report stresses that learning about disability or functional status, chronic illness and its impact on the individual, his family and the community, and developing the ability to work as a team with other health professionals are important elements in the education of all physicians.


Cerebral hemodynamic response to generalized spike-wave discharges.
Data in the literature concerning metabolic demand during generalized spike-wave activity (gSW) are conflicting. We investigated instantaneous changes in cerebral blood flow velocities (CBFV) in both middle cerebral arteries (MCAs) by transcranial Doppler sonography (TCD) during gSW paroxysms recorded by scalp EEG. In 13 patients, CBFVs in both MCAs were averaged, time-locked to the occurrence of the gSW; respiratory rate (RR) and end-expiratory pco2 were measured in one patient. Nine patients showed significant changes in CBFV during gSW. Four had biphasic flow changes with an initial increase (p < 0.05) and a subsequent decrease (p < 0.01). This was partially paralleled by an increase in RR (p < 0.01) and a decrease in pco2 (p < 0.01). In three patients, an increase in CBFV that preceded the onset of gSW by several seconds was observed, followed by a decrease in CBFV. Two patients showed a significant decrease only of CBFV. Only gSWs of a median duration of >0.8 s were associated with significant changes in CBFV. We were able to demonstrate that gSWs of several seconds duration lead to cortical perfusion changes. We suggest that the initial increase of CBFV demonstrated in some patients reflects neuronal activation, whereas the subsequent decrease might in part be due to hyperventilation-induced hypocapnia.


The anterior caudate nucleus supports impulsive choices triggered by pramipexole.
Pramipexole is a dopamine agonist used as a treatment in PD and restless legs syndrome to reduce motor symptoms, but it often induces impulse control disorders. In particular, patients with impulse control disorders tend to make more impulsive choices in the delay discounting task, that is, they choose small immediate rewards over larger delayed ones more often than patients without impulse control disorders and healthy subjects do. Yet the site of action of pramipexole that produces these impulsive choices remains unknown. Based on the heterogeneity of corticostriatal projections and the massive dopamine innervation of the striatum, we hypothesized that impulsive choices triggered by dopamine treatments may be supported by a specific striatal territory. This study aims to determine by which anteriorstriatum territory the Pramipexole trigger impulsive choices; the caudate nucleus, the ventral striatum or the putamen. We compared pramipexole intramuscular injections to intracerebral microinjections within the three striatal territories in healthy monkeys trained to execute the delay discounting task, a behavioral paradigm typically used to evaluate impulsive choices. We found that pramipexole intramuscular injections induced impulsive choices in all monkeys. Local microinjections were performed inside the anterior caudate nucleus, ventral striatum, and anterior putamen and reproduced those impulsive choices when pramipexole was directly injected into the caudate nucleus, whereas injections into the ventral striatum or putamen had no effect on monkeys' choices. These results, consistent with clinical studies, suggest that impulsive choices triggered by pramipexole are supported by the caudate nucleus, allowing us to emphasize the importance of dopamine modulation inside this striatal territory in decision processes underlying impulsive behaviors. © 2019 International Parkinson and Movement Disorder Society.


Telomerized human multipotent mesenchymal cells can differentiate into hematopoietic and cobblestone area-supporting cells.
To compare the hematopoietic support provided by telomerized human mesenchymal stem cells (MSCs) and telomerized MSC-derived stromal cells. We transfected the human telomerase catalytic subunit (hTERT) gene into primary MSCs to establish hTERT-transduced MSCs (hTERT-MSCs). Stromal induction of hTERT-MSCs was performed by replacing the culture medium with Dexter-type culture medium. Hematopoietic support was examined by coculture with cord blood CD34(+) cells. The hTERT-MSCs were morphologically identical with the primary MSCs and expressed surface antigens including CD105, CD73, and CD166. hTERT-MSCs showed a similar doubling time as primary MSCs and continued to proliferate to over 80 population doublings (PD), although the primary MSCs underwent crisis in vitro at 16 PD. The osteogenic, chondrogenic, adipogenic, neurogenic, and stromal differentiation potential of hTERT-MSCs were maintained up to at least 40 PD. The degree of expansion of CD34(+) cells and total number of colony-forming units in culture (CFU-C) upon 12-day coculture with the hTERT-MSC-derived stromal cells were nearly the same as those upon 12-day coculture with hTERT-MSCs (CD34, 33.0-fold+/-2.8-fold vs 36.1-fold+/-1.7-fold of the initial cell number; CFUs, 344.4-fold+/-62.5-fold vs 239.3-fold+/-87.0-fold; CFU-mix, 368.4-fold+/-113.7-fold vs 341.3-fold+/-234.3-fold). However, on day 18 of coculture, the number of cobblestone areas (CA) observed beneath the stromal cells was 15 times higher than that beneath hTERT-MSCs (CA, 146.9+/-54.6 vs 9.4+/-8.1, p<0.01). Stromal induction of hTERT-MSCs exclusively enhanced the support of CA formation provided by hTERT-MSCs. Our human hTERT-MSCs will be useful for elucidating the mechanism of the formation of CAs.


Evaluation of endoscopic ultrasonography for gastric tumors and presentation of three-dimensional display of endoscopic ultrasonography.
We have studied the usefulness of endoscopic ultrasonography (EUS) for: (1) differentiation between extragastric mural compression (EGMC) and submucosal tumors (SMT); (2) qualitative assessment of these lesions; (3) diagnosis of serosal invasion by malignant gastric tumors; (4) presentation of three-dimensional display of EUS findings. A total of 103 patients with submucosal lesions protruding into the gastric lumen on endoscopy were examined. Differentiation between EGMC and SMT could be made by EUS in all cases. Qualitative assessment of these lesions was made by observing their EUS findings, i.e. their internal and marginal echo pattern and their location in the gastric layers. The correct diagnosis was made in 88% (23/26) of EGMC. Of 50 patients with SMT, comprising myogenic tumor (32), aberrant pancreas (8), lipoma (3), gastric cyst (4) and malignant lymphoma (elevated type; 3), differentiation between malignant and benign myogenic tumors was impossible by EUS alone. In addition, 48 patients with advanced gastric cancer and malignant lymphoma were examined. Invasion to the serosal surface was diagnosed as interruption of the fifth layer of the gastric wall. Invasion to other organs was diagnosed by interruption and fusion of the fifth layer into the border of the adjacent structure. Serosal invasion was diagnosed accurately in 65% of 48 patients. Microscopic invasion was difficult to diagnose, and gastric stenosis by tumor was an obstacle to adequate scanning. EUS can be valuable in the differential diagnosis between EGMC and SMT and in the qualitative diagnosis of gastric lesions. It is also effective in detecting serosal invasion by gastric malignant tumors. Three-dimensional display of pathological lesions is new in EUS.(ABSTRACT TRUNCATED AT 250 WORDS)


Adjuvant chemotherapy after resection in elderly Medicare and Medicaid patients with colon cancer.
This study investigated the influence of Medicaid enrollment on the receipt and completion of adjuvant chemotherapy and the likelihood of evaluation by an oncologist for those patients who do not initiate chemotherapy. Medicaid and Medicare administrative data were merged with the Michigan Tumor Registry to extract a sample of patients who had resection for a first primary colon tumor diagnosed between January 1, 1997, and December 31, 2000 (n = 4765). We used unadjusted and adjusted logistic regression to assess the relationship between Medicaid enrollment and the outcomes of interest. Relative to Medicare patients, Medicaid patients were less likely to initiate chemotherapy (odds ratio, 0.50; 95% confidence interval, 0.39-0.65) or complete chemotherapy (odds ratio, 0.52; 95% confidence interval, 0.31-0.85). When the sample was restricted to patients with TNM-staged disease, Medicaid patients were less likely to initiate chemotherapy. Older patients and patients with comorbidities were also less likely to initiate or, in some cases, to complete chemotherapy. Medicaid enrollment is associated with disparate colon cancer treatment, which likely compromises the long-term survival of these patients.


Landscape of clinical trial activity focusing on Indigenous health in Australia: an overview using clinical trial registry data from 2008-2018.
Aboriginal and Torres Strait Islander peoples (hereafter respectfully referred to as Indigenous Australians) represent about 3% of the total Australian population. Major health disparities exist between Indigenous and Non-Indigenous Australians. To address this, it is vital to understand key health priorities and knowledge gaps in the current landscape of clinical trial activity focusing on Indigenous health in Australia. Australian-based clinical trials registered on the Australian New Zealand Clinical Trials Registry or ClinicalTrials.gov from 2008 to 2018 were analysed. Australian clinical trials with and without a focus on Indigenous health were compared in terms of total numbers, participant size, conditions studied, design, intervention type and funding source. Of the 9206 clinical trials included, 139 (1.5%) focused on Indigenous health, with no proportional increase in Indigenous trials over the decade (p = 0.30). Top conditions studied in Indigenous-focused trials were mental health (n = 35, 28%), cardiovascular disease (n = 20, 20%) and infection (n = 16, 16%). Compared to General Australian trials, Indigenous-focused trials more frequently studied ear conditions (OR 20.26, 95% CI 10.32-37.02, p < 0.001), infection (OR 3.11, 95% CI 1.88-4.85, p < 0.001) and reproductive health (OR 2.59, 95% CI 1.50-4.15, p < 0.001), and less of musculoskeletal conditions (OR 0.09, 95% CI 0.00-0.37, p < 0.001), anaesthesiology (OR 0.16, 95% CI 0.01-0.69, p = 0.021) and surgery (OR 0.17, 95% CI 0.01-0.73, p = 0.027). For intervention types, Indigenous trials focused more on prevention (n = 48, 36%) and screening (n = 18, 13%). They were far less involved in treatment (n = 72, 52%) as an intervention than General Australian trials (n = 6785, 75%), and were less likely to be blinded (n = 48, 35% vs n = 4273, 47%) or have industry funding (n = 9, 7% vs 1587, 17%). Trials with an Indigenous focus differed from General Australian trials in the conditions studied, design and funding source. The presented findings may inform research prioritisation and alleviate the substantial burden of disease for Indigenous population.


Marked change in Doppler waveform: report of two cases of subcutaneous hematoma.
We present two cases of subcutaneous hematoma in which color Doppler US revealed colored areas under probe compression, and Doppler waveforms obtained from these areas changed rapidly (from a constant flow to a pulsatile flow, and from a high-velocity flow to a slow-velocity flow) according to the degree of probe compression. In our cases, a sufficient number of blood cells within the lesion moving under probe compression was thought to give rise to Doppler signals and changes in Doppler waveforms.


MR imaging of mediastinal pseudocyst.
Magnetic resonance imaging of a mediastinal pseudocyst clearly demonstrated the entirely intrathoracic location of the pseudocyst.


Postnephrectomy pseudoaneurysm with arteriovenous fistula.
Sonography detected a paraaortic pulsatile tubular mass in a patient 10 years after "stump" nephrectomy, which was subsequently confirmed as a renal artery-renal vein fistula by computed tomography, angiography, and laparotomy.


Distal ureteral obstruction complicating percutaneous nephrolithotomy.
Endourologic techniques for the treatment of surgical stone disease have proved cost-effective and safe with results comparable to open surgical procedures. Because these are new procedures, unexpected complications are going to occur. We have had 3 cases of complete distal ureteral obstruction unrelated to a ureteral calculus following a percutaneous nephrolithotomy. The obstruction resolved after extended nephrostomy tube drainage. These 3 cases and their treatment and pathogenesis are presented.


Polypeptide N-acetylgalactosaminyltransferase-6 expression independently predicts poor overall survival in patients with lung adenocarcinoma after curative resection.
Polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) are important glycosyltransferases in cancer, but the clinical role of its individual isoforms is unclear. We investigated the clinical significance and survival relevance of one isoform, GalNAc-T6 in lung adenocarcinoma after curative resection. GalNAc-T6 was identified in 27.8% (55/198) of patients, and statistically indicated advanced TNM stage (P = 0.069). Multivariate analysis showed GalNAc-T6 to be an independent predictor for reduced overall survival of patients (P = 0.027), and the result was confirmed with bootstraping techniques, and on line "Kaplan-Meier Plotter" and "SurvExpress" database analysis, respectively. Moreover, ROC curve demonstrated that GalNAc-T6 expression significantly improved the accuracy of survival prediction. With 198 paraffin-embedded tumor samples from lung adenocarcinoma patients, GalNAc-T6 expression was immunohistochemically assessed for the association with clinicopathological parameters. The prognostic significance was evaluated by Cox proportional hazards regression analysis with 1000 bootstraping. "Kaplan-Meier Plotter", "SurvExpress" database analysis, and receiver-operating characteristic (ROC) curve were performed to provide further validation. GalNAc-T6 expression correlated significantly with advanced TNM stage, and independently predicted worse OS for lung adenocarcinoma.


The effect of high temperature aging on the corrosion resistance, mechanical property and antibacterial activity of Cu-2205 DSS.
The effects of high temperature aging on the corrosion resistance, mechanical property and antibacterial activity of a copper-bearing 2205 duplex stainless steel (Cu-2205 DSS) were investigated. The results from scanning electron microscopy (SEM), X-ray diffraction (XRD), transmission electron microscopy (TEM) and EDS analysis showed that after aging the proportion of γ phase in microstructure was increased and new σ phase and copper-rich precipitates were formed. The mechanical properties including hardness and tensile and yield strengths of the aged Cu-2205 DSS were significantly enhanced compared to the solution-treated Cu-2205 DSS as well as the 2205 DSS. Electrochemical measurements including electrochemical impedance spectroscopy, potentiodynamic polarization curves and potentiostatic polarization scan were performed to evaluate the corrosion behavior of the Cu-2205 DSS. It was found that aging increased the uniform corrosion resistance but had slightly adverse effect on the pitting corrosion resistance. Additionally, the antibacterial performance of aged Cu-2205 DSS was significantly improved compared to the solution treated Cu-2205 DSS, which was attributed to the more release of copper ions from the matrix that killed the bacteria cells and inhibited the biofilm formation on the surface. The above results suggest that Cu-2205 DSS after high temperature aging revealed good mechanical property, antibacterial performance, and corrosion resistance, which will further expand the application of duplex stainless steel in marine engineering fields.


Relationship between compliance with management target values and renal prognosis in multidisciplinary care for outpatients with chronic kidney disease.
Although multidisciplinary care (MDC) is necessary for controlling chronic kidney disease (CKD), its impact on compliance with management target values in the CKD guidelines remains unclear. This study was designed to clarify the relationship between compliance with management target values and renal prognosis in CKD outpatients who received MDC. There were 255 outpatients with pre-dialysis CKD who received MDC. Achievement rates of systolic, and diastolic blood pressure, hemoglobin, uric acid, low-density lipoprotein cholesterol, and hemoglobin A1c values determined according to CKD guidelines were compared before and 12 months after MDC. In addition, after dividing achievement rates of the target values at 12 months after MDC into four groups (A < 30% ≤ B < 60% ≤ C < 80% ≤ D), dialysis initiation and renal survival rates were compared. There was a significant increase in the overall achievement rate from 62.8 to 69.1% (p < 0.001). The higher the achievement rate after MDC, the lower the dialysis initiation rate (A 72.7%, B 35.3%, C 20.5%, D 8.2%, p < 0.001). There was also a significantly higher renal survival rate (p < 0.001). These findings suggest that MDC for CKD raised awareness of health literacy, and improved the achievement rate of target values. Furthermore, the higher the achievement rate, the later the initiation of dialysis, which led to improvement of renal survival. MDC can improve compliance with management target values for CKD, suggesting that it may improve renal prognosis.


Effects of colchicine on ultrastructure of the lactating mammary cell: membrane involvement and stress on the Golgi apparatus.
The effects of colchicine on ultrastructure of the lactating mammary cell in the rat and goat were studied by electron microscopy. Changes in tissue of the rat were examined over time (1, 2 and 4 h). The goat gland was evaluated by comparing ultrastructure of tissue at the time of maximum milk flow suppression induced by the drug with that of untreated tissue. Colchicine produced notable changes in the tissue of both species: 1) the secretion of lipid droplets and Golgi vesicle contents (exocytosis) was inhibited and the droplets and vesicles became randomly distributed throughout the cell, 2) the Golgi apparatus was significantly reduced in size, 3) casein and lipid continued to be synthesized as evidenced by greater numbers of secretory vesicles and increased sizes of casein micelles and lipid droplets, 4) secretory vesicles showed a propensity to cluster around lipid droplets, 5) isolated microtubules were found occasionally in the control tissue, ordinarily in the vicinity of the Golgi apparatus, but rarely in the colchicine-treated tissue. These observations indicate that colchicine has two effects leading to suppression of exocytosis in the mammary cell: one involves early interference with capacity of secretory vesicle membranes to fuse and a further effect, related to higher concentrations of colchicine, causes intracellular disorganization and loss of polarity. Microtubules were not seen as directly involved in the mechanisms of exocytosis. The secretion of milk fat globules is coupled to exocytosis and thereby is also inhibited by colchicine.


Incorporating weekly carboplatin in anthracycline and paclitaxel-containing neoadjuvant chemotherapy for triple-negative breast cancer: propensity-score matching analysis and TIL evaluation.
The generation of data capturing the risk-benefit ratio of incorporating carboplatin (Cb) to neoadjuvant chemotherapy (NACT) for triple-negative breast cancer (TNBC) in a clinical practice setting is urgently needed. Tumour-infiltrating lymphocytes (TILs) have an established role in TNBC receiving NACT, however, the role of TIL dynamics under NACT exposure in patients receiving the current standard of care is largely uncharted. Consecutive TNBC patients receiving anthracycline-taxane [A-T] +/- Cb NACT at three Institutions were enrolled. Stromal-TILs were evaluated on pre-NACT and residual disease (RD) specimens. In the clinical cohort, propensity-score-matching was used to control selection bias. In total, 247 patients were included (A-T = 40.5%, A-TCb = 59.5%). After propensity-score-matching, pCR was significantly higher for A-TCb vs A-T (51.9% vs 34.2%, multivariate: OR = 2.40, P = 0.01). No differences in grade ≥3 haematological toxicities were observed. TILs increased from baseline to RD in the overall population and across A-T/A-TCb subgroups. TIL increase from baseline to RD was positively and independently associated with distant disease-free survival (multivariate: HR = 0.43, P = 0.05). We confirmed in a clinical practice setting of TNBC patients receiving A-T NACT that the incorporation of weekly Cb significantly improved pCR. In addition, A-T +/- Cb enhanced immune infiltration from baseline to RD. Finally, we reported a positive independent prognostic role of TIL increase after NACT exposure.


Reduced-intensity conditioning followed by allogeneic hematopoietic cell transplantation in myeloid diseases.
Within the past years, reduced or modified doses of chemotherapy or radiotherapy have been widely studied for conditioning before allogeneic hematopoietic cell transplantation in patients with myeloid leukemia not eligible for conventional transplantation. The main goal was to reduce the substantial treatment-related mortality in this patient population while preserving the potential curative graft-versus-leukemia effect. This review summarizes results of published trials using reduced-intensity conditioning (RIC) in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), chronic myeloid leukemia (CML), and myelofibrosis. In most of the published trials conditioning contained fludarabine (90-180 mg/m(2)) in combination with busulfan (4 x 10 mg/kg), melphalan (90-140 mg/m(2)), or 2-5 Gy total body irradiation (TBI). Peripheral blood hematopoietic stem cells from related or unrelated donors were used as graft source in most of the studies. Post-transplantation immunosuppression consisted of cyclosporine combined with methotrexate or mycophenolate mofetil. Although the majority of the patients were above the age of 50 years, early treatment-related mortality was rather low. Nevertheless, the rate of clinically significant graft-versus-host disease (GVHD) seemed to be comparable to conventional transplants in most of the protocols. The outcome differed between trials, but diagnosis and disease status pre-transplant significantly influenced outcome. In summary, this approach is feasible and provides access to the curative potential of allogeneic stem cell transplantation for patients with higher age or comorbidities. Since the majority of the reports included heterogeneous patient populations, mostly with a short follow-up, more and specifically randomized studies are needed to define the role of RIC before allogeneic hematopoietic cell transplantation.


Indocyanine green for successful repair of a long-standing macular hole.
To report on the successful closure of a persistent chronic macular hole using indocyanine green (ICG) during the second surgical approach. Interventional case report. A patient with a long standing macular hole (18 years) underwent pars plana vitrectomy with peeling of the internal limiting membrane (ILM). While no dye was used during the first operation, ICG (0.05%, Pulsion) was applied during the second procedure. The light source was turned off immediately after the ICG application until the dye was washed out after a period of 15 seconds. Tissue harvested during the second surgical approach was prepared for electron microscopy. After the failure of the first operation, areas of incomplete ILM peeling could be stained using ICG and a thorough ILM removal was achieved. Postoperatively, the macular hole was closed, as confirmed by optical coherence tomography. Visual acuity increased from 20/200 to 20/50. No visual field defects were seen postoperatively. There were only few cellular elements adherent to the retinal surface of the ILM as seen during electron microscopy. In cases where tractional forces due to incomplete ILM removal are considered responsible for the persistence of a macular hole, ICG is useful to identify areas of unpeeled ILM. Under certain safety precautions no adverse effect on functional outcome was seen.


Sciatic nerve compression by an extrapelvic cyst secondary to wear debris after a cementless total hip arthroplasty: A case report and literature review.
Polyethylene (PE) wear debris after total hip arthroplasty (THA) may cause formation of a soft tissue mass due to inflammatory reaction. To the best of our knowledge we report the first case in whom the diagnosis was made after examination of the hip, pelvis and lumbar spine with detailed radiological methods and the plain radiographs showed no signs of loosening of the THA. We report a 52 years-old woman who presented with a cyst causing sciatic irritation in her gluteal region due to wear debris after THA. Magnetic resonance imaging (MRI) was useful in detecting the cyst. Resolution of the cyst occured after subtotal cystectomy and revision of the acetabular components. Although plain radiographs can show signs of the underlying pathology; such as osteolysis, loosening of the components and wear of the PE liner, they are unable to detect cystic lesions. Cystic lesions may be an early sign of wear debris. This case shows us that sciatic neuropathy with no evidence of nerve root impingement on lumbar MRI in a patient with THA requires also examination of the hip and pelvis with detailed radiological methods, such as MRI, in addition to plain radiography. Removal of the source of debris via revision surgery following subtotal cystectomy leads to the resolution of the remaining portion of the cyst and also relief of the symptoms of sciatic nerve compression.


Effect of a cholecystokinin antagonist on some effects of diazepam.
Dose responses were evaluated for the effects of diazepam alone or together with the cholecystokinin receptor antagonist CR 1409 on pentetrazole-induced convulsions, motor performance and spontaneous motor activity. The results obtained showed that the cholecytokinin antagonist potentiated the effects of diazepam on motor performance and the anticonvulsant activity of diazepam, while it did not affect spontaneous motor activity. The data presented are consistent with a role for cholecystokinin in some effects of diazepam.


Epiglottic Hemangioma: A Rare Case of Hemoptysis in Adults.
Hemangiomas are benign slow growing vascular tumors of endothelial origin, commonly seen in young. Laryngeal hemangiomas are rare entities with varied clinical presentations depending upon their location and size. We hereby report a rare case of recurrent hemoptysis in a 65-year-old lady with epiglottic hemangioma.


ADVANCE system testing: Can coverage of pertussis vaccination be estimated in European countries using electronic healthcare databases: An example.
The Accelerated Development of VAccine beNefit-risk Collaboration in Europe (ADVANCE) is a public-private collaboration aiming to develop and test a system for rapid benefit-risk (B/R) monitoring of vaccines, using existing healthcare databases in Europe. The objective of this paper was to assess the feasibility of using electronic healthcare databases to estimate dose-specific acellular pertussis (aP) and whole cell pertussis (wP) vaccine coverage. Seven electronic healthcare databases in four European countries (Denmark (n = 2), UK (n = 2), Spain (n = 2) and Italy (n = 1)) participated in this study. Children were included from birth and followed up to age six years. Vaccination exposure was obtained from the databases and classified by type (aP or wP), and dose 1, 2 or 3. Coverage was estimated using period prevalence. For the 2006 birth cohort, two estimation methods for pertussis vaccine coverage, period prevalence and cumulative incidence were compared for each database. The majority of the 2,575,576 children included had been vaccinated at the country-specific recommended ages. Overall, the estimated dose 3 coverage was 88-97% in Denmark (birth cohorts from 2003 to 2014), 96-100% in the UK (2003-2014), 95-98% in Spain (2004-2014) and 94% in Italy (2006-2007). The estimated dose 3 coverage per birth cohort in Denmark and the UK differed by 1-6% compared with national estimates, with our estimates mostly higher. The estimated dose 3 coverage in Spain differed by 0-2% with no consistent over- or underestimation. In Italy, the estimates were 3% lower compared with the national estimates. Except for Italy, for which the two coverage estimation methods generated the same results, the estimated cumulative incidence coverages were consistently 1-10% lower than period prevalence estimates. This study showed that it was possible to provide consistent estimates of pertussis immunisation coverage from the electronic healthcare databases included, and that the estimates were comparable with the national estimates.


A single amino acid change and truncated TM are sufficient for simian immunodeficiency virus to enter cells using CCR5 in a CD4-independent pathway.
Entry of HIV and SIV into susceptible cells is mediated by CD4 and chemokine receptors, which act as coreceptors. To study cell entry of SIV, we constructed a cell line, xKLuSIV, derived from non-susceptible human K562 cells, that express the firefly luciferase reporter gene under control of a minimal SIV long terminal repeat (LTR). Using these susceptible cells, we studied the entry of a well-characterized molecularly cloned macrophage-tropic SIV. xKLuSIV cells that express rhesus macaque CD4 and/or the rhesus chemokine receptor CCR5 are susceptible to infection with the macrophage-tropic, neurovirulent strain SIV/17E-Fr, but only xKLuSIV cells expressing both CCR5 and CD4 were susceptible to infection by the macrophage-tropic, non-neurovirulent strain SIV/17E-Cl. CCR5-dependent, CD4-independent infection by SIV/17E-Fr was abrogated by pre-incubation of the cells with AOP-RANTES, a ligand for CCR5. In addition to viral entry occurring by a CD4-independent mechanism, neutralization of SIV/17E-Fr with rhesus mAbs from 3 different neutralization groups blocked entry into x KLuSIV cells by both CD4-dependent and -independent mechanisms. Triggering the env glycoprotein of SIV-17 EFr with soluble CD4 had no significant effect in infectivity, but triggering of the same glycoprotein of SIV/17E-Cl allowed it to enter cells in a CD4-independent fashion. Using mutant molecular clones, we studied the determinants for CD4 independence, all of which are confined to the env gene. We report here that truncation of the TM at amino acid 764 and changing a single amino acid (R751G) in the SIV envelope transmembrane protein (TM) conferred the observed CD4-independent phenotype. Our data suggest that the envelope from the neurovirulent SIV/17E-Fr interacts with CCR5 in a CD4-independent manner, and changes in the TM protein of this virus are important components that contribute to neurovirulence in SIV.


CFD study on vesicoureteral reflux in the urinary tract with double J stent.
This study investigates the effects of vesicoureteral reflux (VUR) in the upper and lower urinary tracts with and without ureteral stenosis and with a double J stent (DJS). The entire length of the urinary tract with an implanted DJS was modeled. To assess the possibility of VUR, the measured values were used as boundary conditions for the baseline, the maximum cystometric bladder capacity (MCBC) during the filling phase, and maximum vesical pressure during the voiding phase were computed. The flow rates, flow patterns, wall shear stress (WSS) distribution, impact force induced by reflux urination, and helicity of the bladder were investigated for the urinary system. The flow from the bladder to the renal pelvis was detected at maximum vesical pressure (75 cmH2O) during the voiding phase, and a small amount (1.09 mL/s) of VUR was noted at the MCBC during the filling phase. The WSS increased when the reflux was large. Helicity within the bladder varied with the stenosis as well as opening and closing of the urethra. The reflux within the stent was reduced by 40% by inserting a ball into the stent. The main VUR factor was the opening and closing of the vesicoureteric junction by the detrusor muscle. The largest urine reflux (11.7 mL/s) to the kidney occurred when the detrusor muscle was relaxed. Ureteral stenosis affected the VUR and reduced urine reflux. Ball insertion in the stent reduced urine reflux through the stent lumen.


Diagnosis and treatment of venous leakage: a curable cause of impotence.
Sixteen of 149 patients complaining of impotence of a non-neurogenic or endocrine aetiology and with a penile brachial index of greater than 0.7 failed to achieve an erection following intracavernosal injection of 30 mg papaverine and 1 mg phentolamine. All 16 were shown to have a significant venous leak using digital subtraction cavernosography. Nine of the 13 so far operated upon have had a full return of potency. Repeat cavernosography in three failures showed persistent leakage into crural veins in two and non-ligated superficial veins in one. Impotent men with a normal penile brachial index who fail to respond to papaverine and phentolamine have a venous leak, a curable cause of impotence. Surgical access should allow ligation of all identified leaking veins.


Comparison of 4 serological tests--complement fixation, neutralization, fluorescent antibody to membrane antigen and immune adherence hemagglutination--for assay of antibody to varicella-zoster (V-Z) virus.
Four tests for antibody to varicella-zoster (V-Z) virus were compared; these were tests of complement fixation (CF), neutralization (NT), fluorescent antibody to membrane antigen (FAMA) and immune adherence hemagglutination (IAHA). Fifty-two sera from patients with varicella and zoster and from recipients of live varicella vaccine were examined by the 4 tests. The CF test was least sensitive, but the antibody titers by the NT, FAMA and IAHA tests were roughly comparable. The IAHA test was the simplest and fastest to perform, and appeared suitable for routine serological assay to V-Z virus. The correlation between the IAHA antibody titer and susceptibility of individuals to clinical varicella was investigated retrospectively using sera obtained during 2 outbreaks of varicella in an institution for children, where all the unvaccinated children had developed varicella symptoms. Most of the 25 pre-exposure sera from unvaccinated children examined by the IAHA test had tiers of less than 1:2. In contrast, all the 23 sera from vaccinated children who did not develop varicella had detectable antibody titers of 1:2 to 1:64. These results indicate that the IAHA titer reflects the susceptibility or resistance of individuals to clinical varicella.