Conclusions: These results suggest that, even in euthymia, patien

Conclusions: These results suggest that, even in euthymia, patients with BD experience deficits in recognition, identification, and discrimination of facial emotions, with potential functional implications.”
“Circulating tumor cells (CTCs), which have stem cell-like characteristics, might play a crucial

role in cancer metastasis. CD44 has been identified as gastric cancer (GC) stem cell (CSC) marker. Here, the prognostic significance of CD44-positive CTCs in GC patients was investigated. CTCs were detected in 27 of 45 GC patients. The presence of CTCs was significantly associated with lymph node metastasis, distant metastasis, and recurrence (P = 0.007,P = 0.035, and.. = 0.035, resp.). Nineteen of the 27 CTC-positive patients BU-4061T had CD44-positive CTCs. These patients were more likely to develop metastasis and recurrence than patients with CD44-negative CTCs. CD44-positive CTC counts were higher in recurrent patients than in the nonrecurrent ones (means 4.8 and 1.9, resp.;P = 0.010). Furthermore, 13 of 19 patients with CD44-positive CTCs developed recurrent disease, and the mean time to recurrence was shorter than that in patients with CD44-negative CTCs (10.54 +/- 5.55 and 19.13 +/- 9.72 CA4P months, resp.;P =

0.04). COX proportional hazards model indicated that the presence of CD44-positive CTCs and TNM stage were independent predictors of recurrence for GC(P = 0.030 and 0.008). So identifying the stem cell-like CTC subset may provide more clinically useful prognostic information than only detecting CTCs.”
“We describe the vibrational transitions of the donor unit in water dimer with an approach that is based on a three-dimensional local mode model. We perform a perturbative treatment of the intermolecular vibrational modes to improve the transition wavenumber of the hydrogen bonded OH-stretching transition. Kinase Inhibitor Library The model accurately

predicts the transition wavenumbers of the vibrations in water dimer compared to experimental values and provides a physical picture that explains the redshift of the hydrogen bonded OH-oscillator. We find that it is unnecessary to include all six intermolecular modes in the vibrational model and that their effect can, to a good approximation, be computed using a potential energy surface calculated at a lower level electronic structure method than that used for the unperturbed model. (C) 2014 AIP Publishing LLC.”
“In both humans and animals, controversy exists concerning the duration of protection induced by BCG vaccine against tuberculosis (TB) and whether revaccination enhances protection. A long-term study was undertaken to determine whether BCG-vaccinated calves would be protected against challenge with Mycobacterium bovis 21/2 years after vaccination and to determine the effect of revaccination after 2 years.

After the initial

After the initial Bafilomycin A1 analysis of collected data using the software SPSS 18, the pharmacy queuing network performance indicators were calculated for both shifts. Then, based on collected data and to provide appropriate solutions, the queuing system of current situation for both shifts was modeled and simulated

using the software ARENA 12 and 4 scenarios were explored. Results: Results showed that the queue characteristics of the studied pharmacy during the situation analysis were very undesirable in both morning and evening shifts. The average numbers of patients in the pharmacy were 19.21 and 14.66 in the morning and evening, respectively. The average times spent in the system by clients were 39 minutes in

the morning and 35 minutes in the evening. The system utilization in the morning and evening were, respectively, 25% and 21%. The simulation results showed that reducing the staff in the morning from 2 to 1 in the receiving prescriptions stage didn’t change the queue performance indicators. Increasing one staff in filling prescription drugs could cause a decrease of 10 persons in the average queue length and 18 minutes and 14 seconds in the average waiting time. On the other hand, simulation results showed that in the evening, decreasing the staff from 2 to 1 in the delivery of prescription drugs, changed the queue performance indicators very little. Increasing a staff to fill prescription drugs could cause a decrease of 5 persons in the average queue length and 8 minutes and 44 seconds in the average waiting time. Conclusions: The patients’ waiting times and the

number of patients waiting to receive IPI-145 chemical structure services in both shifts could be reduced by using multitasking Batimastat persons and reallocating them to the time-consuming stage of filling prescriptions, using queuing theory and simulation techniques.”
“The aim of this study was to evaluate the effect of increasing the amount of time spent in physical education classes on bone mineral accrual and gain in bone size in prepubertal Danish children. A total of 135 boys and 108 girls, aged 6-8 years, were included in a school-based curriculum intervention program where the usual time spent in physical education classes was doubled to four classes (180 min) per week. The control group comprised age-matched children (62 boys and 76 girls) recruited from a separate community who completed the usual Danish school curriculum of physical activity (90 min/week). Dual-energy X-ray absorptiometry was used to evaluate bone mineral content (BMC; g), bone mineral density (g/cm(2)), and bone width at the calcaneus and distal forearm before and after 3 years of intervention. Anthropometrics and Tanner stages were evaluated on the same occasions. General physical activity was measured with an accelerometer worn for 4 days. In girls, the intervention group had a 12.5% increase (P = 0.

Materials and methods: Twenty-one healthy male professional socce

Materials and methods: Twenty-one healthy male professional soccer players, average 23.2 (+/- 3.6) years old, without history of injury were

selected. The athletes were assessed in an isokinetic dynamometer at three angular velocities: 60, 180 and 300 degrees/s, and from this assessment the peak of torque and calculated H:Q ratio at the three velocities were obtained. The triple hop distance was also used to calculate the hopped distance in meters. Results: No significant difference was found between the lower extremities (dominant and non-dominant) (p = 0.23). Also, a weak relationship between extensor torque and functional test at the three velocities was observed (Dominant: 60 degrees/s_r = 0.38; 180 Sonidegib degrees/s_r = 0.43*; 300 degrees/s_r = 0.26. Non dominant: 60 degrees/s_r = 0.36; 180 degrees/s_r = 0.30; 300 degrees/s_r = 0.48*) (*p <= 0.05). Selleckchem AZD2171 Similar results were found for H:Q ratio (Dominant: 60_r = 0.01; 180_r = 0.11; 300_r = -0.02. Non-dominant: 60_r = -0.20; 180_r = -0.15;

300_r = -0.18). Conclusion: Due to a weak relationship, the isokinetic test cannot be replaced by the triple hop distance (functional test) for muscular function assessment.”
“After modeling the large-scale climate response patterns of leaf unfolding, leaf coloring and growing season length of evergreen and deciduous French temperate trees, we predicted the effects of eight future climate scenarios on phenological events. We used the ground observations

from 103 temperate forests (10 species and 3,708 trees) from the French Renecofor Network and for the period 1997-2006. We applied RandomForest algorithms to predict phenological events from climatic selleck products and ecological variables. With the resulting models, we drew maps of phenological events throughout France under present climate and under two climatic change scenarios (A2, B2) and four global circulation models (HadCM3, CGCM2, CSIRO2 and PCM). We compared current observations and predicted values for the periods 2041-2070 and 2071-2100. On average, spring development of oaks precedes that of beech, which precedes that of conifers. Annual cycles in budburst and leaf coloring are highly correlated with January, March-April and October-November weather conditions through temperature, global solar radiation or potential evapotranspiration depending on species. At the end of the twenty-first century, each model predicts earlier budburst (mean: 7 days) and later leaf coloring (mean: 13 days) leading to an average increase in the growing season of about 20 days (for oaks and beech stands). The A2-HadCM3 hypothesis leads to an increase of up to 30 days in many areas.

For the total embryo group (n = 422), a misdiagnosis rate of 7 1%

For the total embryo group (n = 422), a misdiagnosis rate of 7.1% and a false-negative rate of 3.1% were found. The negative predictive value was 96.1%. Poor morphology Day 4 embryos ( Class 1) were over-represented in the embryo group in which

the blastomere genotype was not confirmed by the whole embryo genotype. The misdiagnosis rate of Class 1 embryos was 12.5% and the false-negative rate 17.1%. Exclusion of these embryos resulted in a misdiagnosis rate of 6.1%, a false-negative rate of 0.5% and a negative predictive value of 99.3%. The two blastomere biopsies revealed a significant ABT263 higher positive predictive value, lowering the misdiagnosis rate, whereas the negative predictive value remained the same. In conclusion, the PGD-PCR procedure is a valid diagnostic method to select unaffected embryos for ET. The misdiagnosis and false-negative rates decrease by rejecting Class 1 embryos for ET. The biopsy of a second blastomere improves the positive predictive value, lowering the misdiagnosis rate.”
“Background. Prolonged bed rest in hospitalized patients leads to deconditioning, impaired mobility, and the potential for longer selleck products hospital stays.\n\nObjective. The purpose of this study was to determine the effectiveness of a nurse-driven mobility protocol to increase the percentage of patients. ambulating during the first 72 hours of their hospital stay.\n\nDesign. A quasi-experimental

design was used before and after intervention in a 16-bed adult medical/surgical intensive care unit (ICU) and a 26-bed adult intermediate care unit (IMCU) at a large community hospital.\n\nMethod. A multidisciplinary team developed and implemented a mobility order set with an embedded algorithm to guide nursing assessment of mobility potential. Based on the assessments, the protocol empowers the nurse to consult physical therapists or occupational therapists

when appropriate. Daily ambulation status reports were reviewed each morning to determine each patient’s activity level. Retrospective Selleck STI571 and prospective chart reviews were performed to evaluate the effectiveness of the protocol for patients 18 years of age and older who were hospitalized 72 hours or longer.\n\nResults. In the 3 months prior to implementation of the Move to Improve project, 6.2% (12 of 193) of the ICU patients and 15.5% (54 of 349) of the IMCU patients ambulated during the first 72 hours of their hospitalization. During the 6 months following implementation, those rates rose to 20.2% (86 of 426) and 71.8% (257 of 358), respectively.\n\nLimitations. The study was carried out at only one center.\n\nConclusion. The initial experience with a nurse-driven mobility protocol suggests that the rate of patient ambulation in an adult ICU and IMCU during the first 72 hours of a hospital stay can be increased.”
“BACKGROUND AND OBJECTIVES: Infection due to Coxiella burnetii (C burnetii), the causative agent of Q fever is rarely sought for in clinical practice.

Results: Our transcriptomic analysis, which highlighted discr

\n\nResults: Our transcriptomic analysis, which highlighted discrepancies between controls and tumor tissues, as well as between various tumor types, led to the identification of 13 genes, allowing discrimination between the thyroid adenomas, oncocytic variants of follicular thyroid tumors, VRT752271 and papillary thyroid carcinomas, whereas the tumors of uncertain malignant potential were found to overlap these classes. Five of these genes (TP53, HOXA9, RUNX1, MYD88, and CITED1), with a differential expression confirmed by qPCR analysis, are implicated

in tumorigenesis, 4 in mitochondrial metabolism (MRPL14, MRPS2, MRPS28, and COX6A1), and 2 in thyroid metabolic pathways (CaMKIINalpha and TPO). The global miRNA analysis revealed 62 differential miRNAs, the expression level for 10 of these being confirmed by qPCR. The differential expression of the miRNAs was in accordance with the modulation of gene expression and the ontologies CA3 solubility dmso revealed by our transcriptomic analysis.\n\nConclusions: These findings reinforce the

classification of follicular thyroid tumors established by the World Health Organization, and our technique offers a novel molecular approach to refine the classification of thyroid tumors of uncertain malignant potential.”
“Purpose of review\n\nChronic obstructive pulmonary disease (COPD) and bronchiectasis are two different but related diseases that occur separately, but can coexist. In this review, we will examine the recent research

regarding patients with COPD who have coexisting bronchiectasis.\n\nRecent findings\n\nRecent research has focused on defining distinct COPD phenotypes with the ultimate goal of changing the outcomes using tailored therapies. A frequent exacerbator phenotype has been identified. COPD patients with Pseudomonas aeruginosa are a phenotype with worse outcomes. Patients with coexisting COPD and bronchiectasis may represent selleck chemicals a unique phenotype.\n\nSummary\n\nPatients with coexisting COPD and bronchiectasis could represent a unique phenotype with more severe disease, worse outcomes, more isolation of potentially pathogenic microorganisms, and more frequent exacerbations, with the potential for targeted therapies.”
“Aging represents a triple threat for myocardial infarction (MI). Not only does the incidence of MI increase with age, but the heart becomes more susceptible to MI induced damage and protective interventions such as ischemic preconditioning (IPC) become less effective.

The difference in depth of focus was significant only between neg

The difference in depth of focus was significant only between negatively aspheric and spherical IOLs. Asphericity differences up to 20 mu m did not influence depth of focus.”
“Mandevilla sanderi is a plant of tropical origin of great horticultural interest because of its abundant flowering and its persistent foliage. Vegetative propagation requires the removal of leafy branches on selleck the mother

plant to produce cuttings. This loss of biomass must be compensated for by the growth of new branches thanks to the mobilization of reserves within the plant. Lack of knowledge about the physiology of this species therefore makes it necessary to characterize its different organs both at the level of their anatomic organization as well as at the level of their ability to store starch. After histological characterization of the different organs (leaves, stems, and roots), starch reserves were localized by histochemical analysis and quantified by biochemical analysis. HDAC inhibitors cancer Starch grains are mainly found in the parenchymatous cortex, the parenchymatous

pith and xylem parenchyma cells, in tuberous roots and stems, and in the palisade and spongy mesophyll of leaves. In 22-week-old plants, the greatest quantity of starch is found in the leaves, whereas the tuberous roots have the highest concentration. The histological description of the different organs of Mandevilla sanderi and the localization of starch reserves allow us to assess the potential role of the different organs in plant growth and development. In the particular case of mother plant management, it is hoped that this knowledge will make it possible to optimize conditions for removing leafy branches.”
“Arbuscular mycorrhizal (AM) and dark septate endophytic (DSE) fungal colonization of Phragmites australis roots and its relation to plant productivity parameters was investigated in an intermittent karst HIF inhibitor wetland Lake Cerknica (Slovenia) with seasonal water level fluctuations. Mycorrhizal colonization was determined five times in 2008-from

the beginning to the end of the growing season-in three reed stands with large differences in soil parameters and water level changes. AM and DSE colonization varied significantly between sampling plots and during the growing season (7% < frequency < 87%). The flooding of two of the three reed stands decreased mycorrhiza early in the growing season, but further flooding had no additional effect. Levels of DSE colonization were high in the beginning and the end of the growing season, while a peak in AM colonization was observed towards the end. The observed positive in situ correlation between mycorrhizal colonization and P. australis growth parameters does not allow final mechanistic conclusion: both P. australis and mycorrhiza could be beneficial. (C) 2010 Elsevier B.V. All rights reserved.

4, 95% CI 1 2 to 4 8, p=0 005) Conclusions The presence of ec

4, 95% CI 1.2 to 4.8, p=0.005).\n\nConclusions The presence of echocardiographic dyssynchrony identifies patients who derive the most improvement from CRT. Patients without dyssynchrony also show more benefit

and less deterioration with CRT than without and should not be denied CRT.”
“New antiviral agents are urgently needed Based on in vitro studies arsenic trioxide (As(2)O(3)) seems to affect viral replication although this has been studied only marginally in vivo In this study the replication of coxsackievirus B3 (CVB3) was studied in Balb/c mice administered 1 mg As(2)O(3)/kg bw once daily during 7 days of infection and in Vero cells exposed for 3 selleck chemicals llc or 5 days to 0 4 2 or 4 mu M As(2)O(3) Viral RNA was measured by reverse transcription PCR (RT-PCR) (in vitro and in vivo) and arsenic concentration was measured by inductively coupled plasma-mass spectrometry (ICP-MS) (in vivo) In vivo As(2)O(3) decreased viral RNA in the brain on days 3 (by 81% p < 0 05) and 7 (by 97% p < 0 01) and in the pancreas on day 7 (by 75% p < 0 05) two of the 5-Fluoracil molecular weight target organs of this infection The results were confirmed in vitro where As(2)O(3) dose-dependently reduced viral RNA with the effect being more pronounced in the surrounding culture medium than inside the infected cells indicating an impaired virion release Thus As(2)O(3) reduced

CVB3 replication both in vitro and in vivo indicating that As(2)O(3) is a viable option in the pursuit of new therapeutic agents against viral infections (C) 2010 Published by Elsevier Masson SAS on behalf of Institut Pasteur”
“Objective: To review primary hyperparathyroidism and the key issues that are relevant to the practicing

endocrinologist.\n\nMethods: The latest information on the presentation, diagnosis, and traditional check details and nontraditional aspects of primary hyperparathyroidism is reviewed.\n\nResults: The diagnosis of primary hyperparathyroidism is straightforward when the traditional hypercalcemic patient is documented to have an elevated parathyroid hormone (PTH) level. Commonly, patients are identified who have normal serum calcium levels but elevated PTH levels in whom no secondary causes for hyperparathyroidism can be confirmed. Traditional target organs of primary hyperparathyroidism the skeleton and the kidneys continue to be a focus in the patient evaluation. Bone mineral density shows a typical pattern of involvement with the distal one-third radius being selectively reduced compared with the lumbar spine in which bone mineral density is generally well maintained. Neurocognitive and cardiovascular aspects of primary hyperparathyroidism, while a focus of recent interest, have not been shown to definitively aid in the decision for or against surgery.

Therefore, C songarica methanol extract may be an effective hepa

Therefore, C. songarica methanol extract may be an effective hepatic protective agent and viable candidate for treating hepatic disorders and other oxidative stress-related diseases.”
“On the basis of pIP501, a green fluorescent protein (GFP)-tagged monitoring tool was constructed for quantifying plasmid mobilization among Gram-positive bacteria and between Gram-positive Enterococcus faecalis and Gram-negative

Escherichia coli. Furthermore, retromobilization of the GFP-tagged monitoring tool was shown from E. faecalis OG1X into the clinical isolate E. faecalis T9.”
“Progressive renal disease is characterized by the accumulation of extracellular matrix proteins in the renal interstitium. Hence, developing agents that antagonize fibrogenic signals is a critical issue facing researchers. The present study investigated CH5424802 supplier the blood-circulation-promoting Chinese herb, safflower, on fibrosis status in NRK-49F GSK2126458 cells, a normal rat kidney interstitial fibroblast, to evaluate the underlying signal transduction mechanism of transforming growth factor-beta (TGF-beta), a potent fibrogenic growth factor. Safflower was characterized and extracted using water. Renal fibrosis model was established both in vitro with fibroblast cells treated with beta-hydroxybutyrate and in vivo using

rats undergone unilateral ureteral obstruction (UUO). Western blotting 5-Fluoracil chemical structure was used to examine protein expression in TGF-beta-related signal proteins such as type I and type II TGF-beta receptor, Smads2/3, pSmad2/3, Smads4, and Smads7. ELISA was used to analyze bioactive TGF-beta 1 and fibronectin levels in the culture media. Safflower extract (SE) significantly inhibited beta-HB-induced fibrosis in NRK cells concomitantly with dose-dependent inhibition of the type I TGF-beta 1 receptor and its down-stream signals (i.e., Smad). Moreover, SE dose-dependently enhanced

inhibitory Smad7. Thus, SE can suppress renal cellular fibrosis by inhibiting the TGF-beta autocrine loop. Moreover, remarkably lower levels of tissue collagen were noted in the nephron and serum TGF-beta 1 of UUO rats receiving oral SE (0.15 g/3 ml/0.25 kg/day) compared with the untreated controls. Hence, SE is a potential inhibitor of renal fibrosis. We suggest that safflower is a novel renal fibrosis antagonist that functions by down-regulating TGF-beta signals.”
“Background: Hyperthyroidism in Graves’ disease is caused by autoantibodies to the TSH receptor (TSHR), and measurement of the TSHR autoantibody (TRAb) yields important information to diagnose and decide on the course of treatment of Graves’ disease. We evaluated basic and clinical performance of a new, rapid, and fully automated electrochemiluminescence immunoassay Elecsys Anti-TSHR (Elecsys TRAb) for measuring serum TRAb.

The precise tissue characterization of lung infections has an imp

The precise tissue characterization of lung infections has an important impact on specific therapeutic treatment. Increased knowledge of significant alterations in lung cancer has led today to a better understanding of the pathogenic substrate underlying the development, progression and metastasis of neoplastic processes. Molecular tests are now routinely performed in different lung tumors allowing a more precise patient stratification in terms BMS-754807 purchase of prognosis and therapy.

This review focuses on molecular pathology of the principal infective lung diseases and tumors.”
“The presentation of alternative treatment plans and the discussion of these options with the adolescent patient is a routine part of both general dental and specialist orthodontic practice. This article will cover the issues involved in obtaining consent for treatment from the adolescent patient and suggests a practical means, if appropriate, to ensure that these patients can give and withdraw consent for their own treatment.”
“The vagus nerve can control inflammatory response through a ‘cholinergic anti-inflammatory pathway’, which is mediated by the alpha 7-nicotinic acetylcholine receptor (alpha 7nAChR) on macrophages. However, Thiazovivin clinical trial the intracellular mechanisms that link alpha 7nAChR

activation and pro-inflammatory cytokine production remain not well understood. In this study, we found that miR-124 is upregulated by cholinergic agonists in LPS-exposed cells and mice. Utilizing miR-124 mimic and siRNA knockdown, we demonstrated that miR-124 is a critical mediator for the cholinergic anti-inflammatory action. Furthermore, our data indicated that miR-124 modulates LPS-induced cytokine production by targeting signal transducer and activator of transcription 3 (STAT3) to decrease

IL-6 production and TNF-alpha converting enzyme (TACE) to reduce TNF-alpha release. These results also indicate that miR-124 is a potential therapeutic target for selleck inhibitor the treatment of inflammatory diseases.”
“Cloning mammals by means of somatic cell nuclear transfer (SCNT) is highly inefficient because of erroneous reprogramming of the donor genome. Reprogramming errors appear to arise randomly, but the nature of nonrandom, SCNT-specific errors remains elusive. We found that Xist, a noncoding RNA that inactivates one of the two X chromosomes in females, was ectopically expressed from the active X (Xa) chromosome in cloned mouse embryos of both sexes. Deletion of Xist on Xa showed normal global gene expression and resulted in about an eight-to ninefold increase in cloning efficiency. We also identified an Xist-independent mechanism that specifically down-regulated a subset of X-linked genes through somatic-type repressive histone blocks. Thus, we have identified nonrandom reprogramming errors in mouse cloning that can be altered to improve the efficiency of SCNT methods.”
“Diabetic status is associated with an increase on oxidative stress markers in humans and animal models.


“Aim:Ghrelin has been implicated as a modulator of num


“Aim:\n\nGhrelin has been implicated as a modulator of numerous physiological pathways. To date, there have not

been any studies describing the role of ghrelin in modulating the chemoreflex control of pulmonary ventilation. Yet the respiratory system impacts, at least to some degree, on virtually all homeostatic control systems. Chronic hypoxia (CH) can cause fundamental changes in ventilatory control, evident by alterations in the acute hypoxia ventilatory response (HVR). As ghrelin plays an important role in metabolic homeostasis, which is tightly linked to ventilatory control, we hypothesized that ghrelin may modulate HVR, especially following CH.\n\nMethods:\n\nWhole body plethysmography Nocodazole concentration was used to measure the HVR (8% O(2) for 10 min) in male Sprague-Dawley rats (body wt similar to 180-220 g) before and after 14 days of CH (CH = 10% O(2)). During CH, rats received daily subcutaneous injections of either saline (control; n = 5) or ghrelin (150 mu g kg-1 day-1; n = 5). The HVR was measured in another four rats that had received

daily injections of ghrelin during normoxia for 7 days.\n\nResults:\n\nGhrelin did not significantly alter basal ventilatory drive or acute HVR in normoxic rats. However, the acute HVR was accentuated following CH in ghrelin-treated rats compared with saline-treated rats.\n\nConclusions:\n\nThese results describe the impact that ghrelin has in altering ventilatory control following CH and, although the mechanisms remain to be fully elucidated, provide guidance for future ghrelin-based studies interpreting physiological data indirectly www.selleckchem.com/products/Nutlin-3.html related to the chemoreflex control of pulmonary ventilation.”
“Prosthetic valve thrombosis (PVT) is one of the most serious long-term complications after heart valve replacement, and optimal treatment remains unclear. The investigators report clinical

characteristics and outcome of all consecutive patients with PVT treated with urgent surgery or thrombolysis with recombinant tissue plasminogen activator at a single BVD-523 datasheet center from January 1988 to December 2008. Thirty-one patients (mean age 59 years, range 20 to 75, 19% men) were diagnosed with PVT a median of 11 years after valve replacement (range 4 months to 32 years). Affected valve positions were mitral in 17 (55%), aortic in 8 (26%), and tricuspid in 6 (19%), and all but 1 were mechanical valves. Eighteen patients underwent urgent surgery, with 2 deaths in the immediate perioperative phase and 2 recurrences (11%) of PVT over a median follow-up period of 76 months. Of 13 patients treated with thrombolysis, there was immediate clinical improvement after a single administration of recombinant tissue plasminogen activator in 12 (92%), of whom 8 (61%) showed complete response with normalization of echocardiographic findings. The only nonresponder was subsequently referred for urgent surgery.