Automated radiolabelling of [68Ga]Ga-PSMA-11 (gallium (68Ga)-gozetotide) using the Locametz® kit and two generators.

BACKGROUND: Steps have been taken by pharmaceutical companies to obtain marketing authorisation of PSMA ligands in the European Union. Since December 2022, Locametz® (PSMA-11, gozetotide) is licensed as kit for manual radiolabelling with gallium-68 and commercially available since mid-2023. The Summary of Product Characteristic (SmPC) describes manual radiolabelling with a maximum activity after radiolabelling of 1369 MBq. We aimed for radiolabelling with a higher activity to increase production efficiency, and thus, automated radiolabelling is strongly preferred over manual radiolabelling to reduce radiation exposure to personnel. The aim of this study was to develop and validate a method for automated radiolabelling of the Locametz® kit using ~ 2000 MBq of gallium-68 eluate for radiolabelling. RESULTS: Automated radiolabelling of [68Ga]Ga-PSMA-11 using the Locametz® kit provided a product which complies to the Ph. Eur., had a shelf-life of 6 h at room temperature, and theoretically reduced radiation exposure 5.7 times. Radiolabelling with one and two generator(s) resulted in a radiochemical yield of 91-102% and 96-101% after preparation, respectively. The radiochemical purity ranged from 98.0 to 99.6% for radiolabelling with one generator and ranged from 98.4 to 99.3% for radiolabelling with two generators with similar stability. The activity of the final product was much higher when using two generators, 1961-2035 MBq compared to 740-1260 MBq, which leads to ~ 1.5 times more patient syringes available per preparation. CONCLUSION: Automated radiolabelling of [68Ga]Ga-PSMA-11 using the Locametz® kit with higher gallium-68 activity than specified in the SmPC results in a product that is in compliance with the Ph. Eur. monograph and has a shelf-life of 6 h at room temperature. Radiolabelling with two generators proved possible and resulted in a product with similar quality but with much higher efficiency.

A rise in the frequency of lasR mutant Pseudomonas aeruginosa among keratitis isolates between 1993 and 2021.

Introduction: Pseudomonas aeruginosa causes vision threatening keratitis. The LasR transcription factor regulates virulence factors in response to the quorum sensing molecule N-3-oxo-dodecanoyl-L-homoserine lactone. P. aeruginosa isolates with lasR mutations are characterized by an iridescent high sheen phenotype caused by a build-up of 2-heptyl-4-quinolone. A previous study demonstrated 22% (n=101) of P. aeruginosa keratitis isolates from India between 2010 and 2016 were sheen positive lasR mutants, and the sheen phenotype correlated with worse clinical outcomes for patients. In this study, a longitudinal collection of P. aeruginosa keratitis isolates from Eastern North America were screened for lasR mutations by the sheen phenotype and sequencing of the lasR gene. Methods: Keratitis isolates (n=399) were classified by sheen phenotype. The lasR gene was cloned from a subset of isolates, sequenced, and tested for loss of function or dominant-negative status based on an azocasein protease assay. A retrospective chart review compared outcomes of keratitis patients infected by sheen positive and negative isolates. Results: A significant increase in sheen positive isolates was observed between 1993 and 2021. Extracellular protease activity was reduced among the sheen positive isolates and a defined lasR mutant. Cloned lasR alleles from the sheen positive isolates were loss of function or dominant negative and differed in sequence from previously reported ocular lasR mutant alleles. Retrospective analysis of patient information suggested significantly better visual outcomes for patients infected by sheen positive isolates. Discussion: These results indicate an increase in lasR mutations among keratitis isolates in the United States and suggest that endemic lasR mutants can cause keratitis.

Rise in frequency of lasR mutant Pseudomonas aeruginosa among keratitis isolates between 1993 and 2021.

Pseudomonas aeruginosa causes severe vision threatening keratitis. LasR is a transcription factor that regulates virulence associated genes in response to the quorum sensing molecule N-3-oxo-dodecanoyl-L-homoserine lactone. P. aeruginosa isolates with lasR mutations are characterized by an iridescent high sheen phenotype caused by a build-up of 2-heptyl-4-quinolone. A previous study indicated a high proportion (22 out of 101) of P. aeruginosa keratitis isolates from India between 2010 and 2016 were sheen positive and had mutations in the lasR gene, and the sheen phenotype correlated with worse clinical outcomes for patients. In this study, a longitudinal collection of P. aeruginosa keratitis isolates from Eastern North America were screened for lasR mutations by the sheen phenotype and sequencing of the lasR gene. A significant increase in the frequency of isolates with the sheen positive phenotype was observed in isolates between 1993 and 2021. Extracellular protease activity was lower among the sheen positive isolates and a defined lasR mutant. Cloned lasR alleles from the sheen positive isolates were loss of function or dominant negative and differed in sequence from previously reported ocular lasR mutant alleles. Insertion elements were present in a subset of independent isolates and may represent an endemic source from some of the isolates. Retrospective analysis of patient information suggested significantly better visual outcomes for patients with infected by sheen positive isolates. Together, these results indicate an increasing trend towards lasR mutations among keratitis isolates at a tertiary eye care hospital in the United States.

Neoadjuvant tyrosine kinase inhibitor therapy in locally advanced differentiated thyroid cancer: a single centre case series.

OBJECTIVE: Primary surgical resection remains the mainstay of management in locally advanced differentiated thyroid cancer. Tyrosine kinase inhibitors have recently shown promising results in patients with recurrent locally advanced differentiated thyroid cancer. This study discussed four patients with locally advanced differentiated thyroid cancer managed with tyrosine kinase inhibitors used prior to surgery in the 'neoadjuvant' setting. METHOD: Prospective data collection through a local thyroid database from February 2016 identified four patients with locally advanced differentiated thyroid cancer unsuitable for primary surgical resection commenced on neoadjuvant tyrosine kinase inhibitor therapy. RESULTS: All cases had T4a disease at presentation. Three cases tolerated tyrosine kinase inhibitor therapy for more than 14 months while the last case failed to tolerate treatment at 1 month. All patients subsequently underwent total thyroidectomy to facilitate adjuvant radioactive iodine treatment. Disease-specific survival remains at 100 per cent currently (range, 29-75 months). CONCLUSION: Neoadjuvant tyrosine kinase inhibitors in locally advanced differentiated thyroid cancer can be effective in reducing primary tumour extent to potentially facilitate a more limited surgical resection for local disease control.

A next generation sequencing (NGS) analysis to reveal genomic and proteomic mutation landscapes of SARS-CoV-2 in South Asia.

Counts for SARS-CoV-2 associated infections and fatalities are on the rise globally even in regions which contained the spread momentarily. The pattern of infections has been found to be controlled by the distinctive selection pressures exerted by fluctuating environmental nature and hosts. A total of 410 whole-genome sequences submitted by the South Asian countries were retrieved from the GISAID database and analyzed to assess the impact and pattern of mutations in this region. Most common and frequent mutations in the South Asian countries are 241C > T, 3037C > T, 14408C > T, and 23403A > G and about 85% SNPs are localized in ORF1ab, spike protein, and nucleocapsid. Among the identified mutations, the proportion of missense type (54.17%) was highest, followed by the synonymous (41.66%) and the non-coding types (4.17%). While analyzing transmission source in terms of geolocation, the largest clustered group from the South Asian countries was based on the G-clade (D614G) (81.7%; 335/410 samples), tracing the inception and transmission of SARS-CoV-2 infections in the South Asian countries from European regions. Phylogenetic analysis also revealed that the South Asian strains are highly related to the South American and European strains. We found that G-clade mutations are more prevalent (96.19%) in the samples of Bangladesh which were also prevalent in the European isolates. Surprisingly, one missense mutation (1163A > T) in ORF1ab gene became dominant only in Bangladesh (78.8%), which led to debates regarding effects on the pathogenicity and transmissibility of the virus. Overall, the findings of this study highlight the frequently mutated SARS-CoV-2 variants among the COVID-19 patients in the South Asian countries which might ease containment of the disease in this region through investigating the virulence reducing factors as the identified mutations are strongly correlated with low infection and mortality rate.

Characterization of a new bacteriocin-like inhibitory peptide produced by Lactobacillus sakei B-RKM 0559.

The biopreservation strategy allows extending the shelf life and food safety through the use of indigenous or controlled microbiota and their antimicrobial compounds. The aim of this work was to characterize an inhibitory substance with bacteriocin-like activity (Sak-59) produced by the potentially probiotic L. sakei strain from artisanal traditional Kazakh horse meat product Kazy. The maximum production of Sak-59 occurred at the stationary phase of the L. sakei growth. Sak-59 showed inhibitory activity against gram-positive meat spoilage bacteria strains of Listeria monocytogenes, Staphylococcus aureus, and pathogenic gram-negative bacteria strains of Serratia marcescens and Escherichia coli, but not against the tested Lactobacilli strains. Sak-59 activity, as measured by diffusion assay in agar wells, was completely suppressed after treatment with proteolytic enzymes and remained stable after treatment with α-amylase and lipase, indicating that Sak-59 is a peptide and most likely not glycosylated or lipidated. It was concluded that Sak-59 is a potential new bacteriocin with a characteristic activity spectrum, which can be useful in the food and feed industries.

Cost-Effectiveness of Immune Checkpoint Inhibitors in Urothelial Carcinoma-A Review.

Over the last decade, an increasing number of immune checkpoint inhibitors (ICIs) have been assessed for therapeutic efficacy in urothelial carcinoma (UC). The high cost has prompted multiple cost-effectiveness analyses for the various disease stages, with no established consensus. We reviewed the literature to assess the available cost-effectiveness studies and summarize their findings. Studies were filtered for a calculated incremental cost-effectiveness ratio (ICER) to standardize comparison. Over 2600 articles were narrowed to eight primary investigations: one for BCG-refractory non-muscle invasive (NMI), one for neoadjuvant therapy in muscle-invasive (MI), and six for advanced disease. Cost-effectiveness was not achieved for NMI disease. Atezolizumab met the willingness-to-pay (WTP) threshold as neoadjuvant therapy for MI disease compared to chemotherapy, but with multiple limitations on the interpretation. Of the six studies on advanced disease, the results were mixed. This was at least partially attributable to varied methodologies including extrapolated time horizons, inconsistent cost inputs, and different WTP thresholds. Overall, the aggregate results were not compelling enough to establish ICIs as cost-effective compared to conventional chemotherapy. Value may improve with continued investigation into long-term outcomes, refined patient selection, and pricing discounts.

Continuous intraoperative nerve monitoring in thyroidectomy using automatic periodic stimulation in 256 at-risk nerves.

INTRODUCTION: Automatic periodic stimulation of the vagal nerve during thyroidectomy provides real-time feedback of recurrent laryngeal nerve function intraoperatively. To assess the validity of this device, the ability of monitoring to predict recurrent laryngeal nerve palsy was determined and the incidence of recurrent laryngeal nerve palsy recorded. MATERIALS AND METHODS: All thyroidectomies using APS® (Automatic Periodic Stimulation, Medtronic) nerve monitoring were reviewed over a 27-month period. Changes in signal amplitude and latency during thyroidectomy were recorded from saved data. Postoperative fibreoptic laryngoscopy determined the incidence of vocal cord immobility and recovery of nerve function was assessed from follow-up letters. RESULTS: A total of 256 at-risk nerves were examined (132 hemi- and 62 total thyroidectomies) in cases involving benign and malignant disease. Permanent recurrent laryngeal nerve palsy occurred in six (2.3%) lobectomies and transient recurrent laryngeal nerve palsy occurred in two lobectomies (< 1%). Sensitivity for detecting postoperative vocal cord immobility was 100% and specificity 85% if the end amplitude was 50% below baseline. The positive predictive value when amplitude was 50% below baseline was 18%. The negative predictive value when amplitude was 50% above or equal to baseline was 100%. Intraoperatively, the amplitude was 50% below baseline more frequently in the vocal cord immobility group (t-test, P < 0.015). No vagal nerve complications occurred. CONCLUSION: Whilst the incidence of recurrent laryngeal nerve palsy is comparable to rates in the literature, the incidence of transient palsy is lower than published averages. APS is able to reliably predict recurrent laryngeal nerve palsy based on end amplitude.

Examining the acute effects of retrograde versus low mean shear rate on flow-mediated dilation.

Arterial endothelial function is acutely and chronically regulated by blood flow-associated shear stress. An acute intervention employing modest forearm cuff occlusion to simultaneously increase retrograde and decrease mean brachial artery shear rate for 30 min evokes transient impairments in flow-mediated dilation (FMD). However, the independent influence of the low mean versus the retrograde shear stress components is unclear. Healthy young adults [n = 24 (12 women, 12 men); 22 ± 2 yr, body mass index = 25 ± 2 kg/m2 (mean ± SD)] completed three laboratory visits within 1 wk. Visits consisted of 45 min of supine rest followed by a brachial artery FMD test (duplex ultrasound) before and after a 30-min intervention: control (shear rate unchanged), cuff (mean shear rate decreased, retrograde shear rate increased), or arterial compression (mean shear rate decreased, no increase in retrograde shear rate). The mean shear rate on the compression visit was targeted to match that achieved on the cuff visit. Cuff and compression trials decreased mean shear rate to a similar extent (cuff: 43 ± 22 s-1, compression: 43 ± 21 s-1; P = 0.850) compared with control (65 ± 21 s-1; both P < 0.001), with the retrograde component elevated only in the former (cuff: -83 ± 30 s-1, compression: -7 ± 5 s-1; P < 0.001). FMD decreased by 29 ± 30% (P < 0.001) after the cuff intervention and 32 ± 24% (P < 0.001) after the compression trial but was unchanged on the control visit (-0.3 ± 18%; P = 0.754). This was not altered by accounting for the shear rate stimulus. An increased retrograde shear stress does not appear to be obligatory for the transient reduction in FMD achieved after a 30-min exposure to low mean shear stress. These findings provide novel mechanistic insight on the regulation of endothelial function in vivo. NEW & NOTEWORTHY Low mean and retrograde shear stress are considered atherogenic; however, their relative contribution to the acute regulation of endothelial function in humans is unclear. Matched reductions in mean shear stress (30 min), with and without increases in retrograde shear stress, elicited equivalent reductions in flow-mediated dilation in men and women. These findings afford novel insight regarding the shear stress components governing the acute (dys)regulation of conduit artery endothelial function in vivo.

The incidence of post-thyroidectomy hypocalcaemia: a retrospective single-centre audit.

INTRODUCTION: The aim of this single centre retrospective observational record-based audit was to assess the incidence of post-thyroidectomy hypocalcaemia. The setting was a district general hospital in Hertfordshire covering a population of 500,000 people. A total of 196 patients who had had total or completion thyroidectomy during a five-year period were included in the study. MATERIALS AND METHODS: The primary outcome measure was to determine the rate of biochemical and symptomatic hypocalcaemia in patients undergoing total or completion thyroidectomy. Secondary outcome measures assessed time taken for biochemical and clinical hypocalcaemia to resolve, whether malignancy affected the rate of hypocalcaemia and if removal of parathyroid glands during surgery were a predictor of hypocalcaemia. RESULTS: The overall incidence of post-thyroidectomy hypocalcaemia (PTHC) within 24 hours was 21.4%. The incidence increased from 6 hours (13.8%) to 24 hours post-thyroidectomy (15.8%) and there was evidence of both transient and delayed PTHC within the first 24 hours. By 6 months post-surgery, 3.6% remained hypocalcaemic and required continual oral supplementation. Patients with benign thyroid disease had a higher risk of PTHC (P = 0.04) and patients younger than 50 years of age had a higher risk of symptomatic hypocalcaemia (P = 0.016). Other clinical factors including sex, type of surgery, neck dissection, oral calcium and/or vitamin D supplementation and inadvertent histological parathyroid gland excision were not associated with an increased incidence of PTHC or symptomatic hypocalcaemia. CONCLUSIONS: Our audit shows that the rate of PTHC within our population was below the national average with higher risk in benign thyroid disease.

Effect of positioning on ureteric stone retropulsion: 'gravity works'.

OBJECTIVE: To evaluate the potential impact of alterations in 'patient' position on laser-induced ureteric stone retropulsion in an in vitro model. MATERIALS AND METHODS: A ceramic (phantom) stone was placed in a water-filled clear polymer tube and subjected to continuous laser energy until the stone had retropulsed a distance of 10 cm. The trial was stopped after 60 s if the stone had not reached 10 cm. The time and total energy needed to cause 10 cm of retropulsion were recorded at incline angles of 0°, 10°, 20°, and 40°; 10 trials at each angle were completed. The study was then repeated with pure calcium phosphate brushite stones. RESULTS: Retropulsion decreased with increasing incline angle of the saline-filled clear polymer tube. At 0° of incline the phantom stone reached a distance of 10 cm after 7.4 s. At 10°, 20° and 40°, the phantom stone migrated a mean maximum distance of 3.1, 1.2 and 0.7 cm, respectively, and the trial was stopped after 60 s. For the calcium phosphate stone, at 0° and 10° of incline, the stone reached 10 cm after 6.9 and 42.8 s, respectively (P < 0.05). At 20° and 40°, the calcium phosphate stone moved a mean maximum distance of 2.4 and 1 cm, and the trial was stopped after 60 s. CONCLUSION: Alterations in the angle of inclination reduced stone retropulsion during ureteroscopic lithotripsy in an in vitro model to <1 cm. Increasing the incline angle of a patient may effectively preclude retropulsion when performing laser lithotripsy of ureteric stones.

Patients presenting to a Men's Health clinic are at higher risk for depression, insomnia, and sleep apnea.

Depression and sleep problems are highly prevalent disorders that are often comorbid with other medical disorders. We evaluated the prevalence and associations of these conditions in patients presenting to a Men's Health clinic. In this retrospective study, 124 patients presenting to a Men's Health clinic completed three urological questionnaires (International Index of Erectile Function [IIEF-5], International Prostate Symptom Score [IPSS], and Androgen Deficiency in Aging Males [ADAM]); and four non-urological questionnaires (Patient Health Questionnaire for depression [PHQ-9], STOP-BANG Sleep Apnea [OSA STOP-BANG], Insomnia Severity Index [ISI], and Epworth Sleepiness Scale [ESS]). Questionnaire results were evaluated in conjunction with patient clinical history and associated laboratory values via univariate and multivariate analysis. The mean age of the study participants was 54.1 years (SD 16). Comorbidities included hypertension (22.5%), vascular disease (15%), and diabetes mellitus (13.3%). Body Mass Index (BMI) was >25 in 77.3%. IIEF-5 scores were moderate-severe in 47.9%, ADAM questionnaire was positive in 79%, and IPSS scores were moderate-severe in 42.9% of patients. PHQ-9 demonstrated mild-severe depression in 38.6%, STOP-BANG showed intermediate-high risk for sleep apnea in 55.2%, ISI indicated moderate-severe insomnia in 18.1%, and ESS revealed mild-severe sleepiness in 16.6% of participants. On univariate analysis, BMI was associated with scores on the PHQ-9 (p = 0.035), STOP-BANG (p < 0.001), and ESS (p < 0.006). On multivariate analysis, positive ADAM questionnaire was associated with STOP-BANG (OR 3.29, 95% CI: 1.012-10.69), and IPSS with PHQ-9 (OR 4.64, 95% CI: 1.40-15.43) and ISI (OR 3.27, 95% CI: 1.06-10.1). Overall, patients presenting to a Men's Health Clinic were found to have high prevalence rates for risk of depression, insomnia and sleep apnea. Risks were elevated in older subjects, and those with increased BMI, hypogonadism, and lower urinary tract symptoms. Appropriate screening and referral to appropriate specialists are encouraged.

Release of Moxifloxacin From Corneal Collagen Shields.

OBJECTIVES: To investigate the diffusion of moxifloxacin through bandage contact lenses (BCLs) versus corneal collagen shields (CSs), the relative ability of BCLs and CSs to release moxifloxacin, and the potential of release of moxifloxacin from CSs in the clinical setting. METHODS: Using an in vitro model, the diffusion of 5% moxifloxacin across BCLs and CSs was compared. Next, the amount of drug release from BCLs and CSs soaked in 0.5% moxifloxacin was measured. Finally, based on a clinical model, CSs were soaked in Vigamox (commercial moxifloxacin) and the total concentration released was detected. Collagen shields remained intact after 24 hr; therefore, enzymatic digestion and mechanical grinding of the CS were performed to determine whether further drug could be released. The concentration of moxifloxacin was measured using a spectrophotometer at set time points up to 24 hr. RESULTS: In the diffusion assay, 35.7±10.5% diffused through the BCLs and 36.2±11.8% diffused through the CSs (P=0.77). The absorption assay demonstrated at 120 min, a total of 33.3±6.77 µg/mL was released from BCLs compared with 45.8±5.2 µg/mL from the CSs (P=0.0008). In vitro experiments to simulate clinical application of Vigamox-soaked CS found the concentration of moxifloxacin released of 127.7±7.25 µg/mL in 2 mL of phosphate-buffered saline over 24 hr. CONCLUSIONS: Moxifloxacin diffuses through BCLs and CSs at similar rates; however, CSs have greater capacity to absorb and release moxifloxacin compared with BCLs. Vigamox-soaked CSs released 250 µg of moxifloxacin and may be a useful method to prevent endophthalmitis.

Outcomes after DSEK in 101 eyes with previous trabeculectomy and tube shunt implantation.

PURPOSE: The aim of this study was to determine the outcomes after Descemet stripping endothelial keratoplasty (DSEK) in eyes with previous glaucoma surgery. METHODS: This is a retrospective review of all DSEK procedures performed by 2 surgeons from May 1, 2006, to December 31, 2012. RESULTS: Four hundred sixty-two DSEK procedures were performed, of which 113 (24%) were performed in 101 eyes after a trabeculectomy (52 procedures) and/or tube shunt implantation (76 procedures) (15 procedures in eyes with both). Primary graft failure and donor dislocation developed in 4.4% and 14.2% of cases in eyes with previous glaucoma surgery, not significantly different from the 3.2% (P = 0.56) and 11.5% (P = 0.51) in eyes without prior glaucoma surgery. During a mean follow-up of 20.7 ± 17.6 months, endothelial rejection developed in a greater percentage of eyes with previous glaucoma surgery (12.9%; 0.069/eye-year) compared with that in eyes without surgery (6.9%; 0.042/eye-year), although the difference was not statistically significant (P = 0.066 for percentage of eyes; P = 0.16 for rejection rate). Secondary graft failure developed in a significantly higher percentage of eyes with previous glaucoma surgery (15.9%; 0.094/eye-year) compared with that in eyes without surgery (3.2%; 0.019/eye-year) (P < 0.0001; P < 0.0001). Elevated intraocular pressure after DSEK was significantly more common in eyes with medically treated glaucoma (41.3%; 0.345/eye year) than in eyes with a previous glaucoma surgery (23.8%; 0.145/eye-year) and without glaucoma (20.0%; 0.138/eye year) (P = 0.009; P = 0.007). CONCLUSIONS: Although intraoperative and early postoperative complications such as donor dislocation and primary graft failure are not significantly more common after DSEK in eyes with previous glaucoma surgery, secondary graft failure is. In contrast, other postoperative complications such as elevated intraocular pressure are significantly more common in eyes with medically treated glaucoma than in eyes with previous glaucoma surgery and without glaucoma.

Epidemiological Study of Youth Mental Health Using Strengths and Difficulties Questionnaire (SDQ).

BACKGROUND: Prevention and treatment of youths` mental disorders are important, not just for to diminish their present problems but to improve their functions in adulthood. This study was performed to evaluate the mental health status of 6-18 years old youths in a community-based sample using the strength and difficulties questionnaire (SDQ). METHODS: Parent of 2000 youths (6-18 years old) were selected from 250 clusters from different municipality areas of Isfahan, Iran and they responded to extended version of SDQ parent`s form. The mean score in each subscale and prevalence of symptom and relation with some demographic features were determined. RESULTS: The total score of SDQ was 26%, means that 26% of youth had psychiatric problems. By determining the subscale score, it reveals that conduct disorder (34.7%) was the most common problem in youth followed by peer relationship problems (25.4%), emotional problems (24.5%), hyperactivity (23%) and impairment of prosocial behavior (5.7%). CONCLUSION: Our findings showed that mental health of youth population in Isfahan especially the conduct problem needs more attention.

Solitary fibrous tumor of the pleura.

BACKGROUND: The aim of this study was to evaluate the clinical behavior of solitary fibrous tumors of the pleura and consider the optimal surgical approach for these rare tumors. MATERIAL AND METHODS: We retrospectively reviewed the records of nine patients who underwent thoracotomy for tumor resection in our clinic between 1997 and 2006. RESULTS: Nine patients were operated in this period and their median age was 46 years. None of them had been exposed to asbestos. Symptoms were present in 8 patients. All patients underwent thoracotomy. The tumor originated from the visceral pleura in 7 patients and was parietal in 2. All tumors were totally excised. The median diameter of the tumors was 9 cm (range 4-24 cm). Pathological investigation reported the tumors to be a benign solitary fibrous tumor of the pleura in all 9 patients. Resection was complete in all patients. There was no postoperative mortality and no major complications. No recurrence was observed during a median follow-up of 74 months. CONCLUSIONS: Solitary fibrous tumors of the pleura are rare neoplasms and can have giant diameters. Complete surgical resection is the optimal treatment. The risk of malignant transformation of such large masses should be borne in mind.

Vibrational modes of metal nanoshells and bimetallic core-shell nanoparticles.

We theoretically study the spectrum of radial vibrational modes in composite metal nanostructures such as bimetallic core-shell particles and metal nanoshells with dielectric core in an environment. We calculate frequencies and damping rates of fundamental (breathing) modes for these nanostructures along with those of two higher-order modes. For metal nanoshells, we find that the breathing mode frequency is always lower than the one for solid particles of the same size, while the damping is higher and increases with a reduction in the shell thickness. We identify two regimes that can be characterized as weakly damped and overdamped vibrations in the presence of external medium. For bimetallic particles, we find periodic dependence of frequency and damping rate on the shell thickness with period being determined by the mode number. For both types of nanostructures, the frequency of higher modes is nearly independent of the environment, while the damping rate shows a strong sensitivity to the outside medium.

Circulating soluble adhesion molecules ICAM-1 and VCAM-1 and their association with clinical outcome, troponin T and C-reactive protein in patients with acute coronary syndromes.

OBJECTIVES: The aim of this study was to compare concentrations of soluble intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) in patients with coronary artery disease and healthy control and to evaluate the usefulness of the inflammatory markers as predictors of adverse prognosis in patients with acute coronary syndromes (ACS). DESIGN AND METHODS: ELISA was used to measure sICAM-1 and sVCAM-1 levels in 75 patients with ACS, 36 patients with stable angina pectoris (SAP) and 25 healthy subjects. hsCRP was measured with immunoturbidimetric assay, cardiac troponin T-with electrochemiluminescence immunoassay. RESULTS: All soluble ICAM-1 and VCAM-1 significantly discriminated between patients with ACS and SAP (p=0.014 and 0.05, respectively) and control subjects (p<0.001 and 0.05). During the 6-month follow-up of the patients with ACS, there were 28 major cardiac events (37.3%). The odds ratio associated with the highest value of sVCAM-1 was 4.62 (95% CI 1.8-11.4, p=0.0009) without adjustment and remained significantly elevated after adjustment for cTnT (RR 3.93, 1.5-10, p=0.04) and hsCRP (RR 2.22, 0.8-5.7, p=0.05). In contrast, an elevated level of sICAM-1 was not associated with future coronary risk after adjustment for cTnT and hsCRP. CONCLUSIONS: In patients with acute coronary syndromes, VCAM-1 serum levels powerfully predict an increased risk for subsequent cardiovascular events and extend the prognostic information gained from traditional biochemical markers.

Thermodynamic aspects of dicarboxylate recognition by simple artificial receptors.

Recognition of dicarboxylates by bis-functional hydrogen-bonding receptors displays divergent thermodynamics in different solvent systems. NMR titration and isothermal titration calorimetry indicated that neutral bis-urea and bis-thiourea receptors form exothermic complexes with dicarboxylates in DMSO, with a near zero entropic contribution to binding. The increased binding strength of bis-guanidinium receptors precluded quantitative measurement of binding constants in DMSO, but titration calorimetry offered a qualitative picture of the association. Formation of these 1:1 complexes was also exothermic, but additional endothermic events occurred at both lower and higher host-guest ratios. These events indicated multiple binding equilibria but did not always occur at a discrete 2:1 or 1:2 host-guest molar ratio, suggesting higher aggregates. With increasing amounts of methanol as solvent, bis-guanidinium receptors form more endothermic complexes with dicarboxylates, with a favorable entropy of association. This switch from association driven by enthalpy to one driven by entropy may reflect a change from complexation involving the formation of hydrogen bonds to that promoted by solvent liberation from binding sites.