Isolation and Characterization of Novel Polymorphic Microsatellite Loci in <Emphasis Type="Italic">Hippophae rhamnoides</Emphasis>

Hippophae rhamnoides L. belonging to family Elaeagnaceae has been a species of interest due to its high nutritional value. In the present study, a set of 26 novel microsatellites from Hippophae developed from an enriched genomic library using biotin labelled di, tri and tetra nucleotide repeats have been reported. Out of 108 clones sequenced, only 62 fragments comprised of microsatellites. All the 26 designed primers showed amplification and 14 highly polymorphic markers were selected and genotyped in 24 Hippophae accessions. The number of alleles ranged from 3 to 7 alleles per locus with an average of 5. The average genetic distance among these accessions was 0.64. Polymorphic information content ranged from 0.47 to 0.79. Mean expected heterozygosity (H_e) and observed heterozygosity (H_o) were 0.69 and 0.43 respectively. Hardy–Weinberg and Linkage disequilibrium showed that all 14 polymorphic loci were in HWE (P < 0.005) with significant linkage disequilibrium between pairs of loci. These new sets of microsatellite markers are expected to be especially useful in future for linkage mapping, varietal identification and genetic diversity studies.     

<Emphasis Type="Italic">In Vivo</Emphasis> DCE-MRI for the Discrimination Between Glioblastoma and Radiation Necrosis in Rats

Purpose

In this study, the potential of semiquantitative and quantitative analysis of dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) was investigated to differentiate glioblastoma (GB) from radiation necrosis (RN) in rats.

Procedures

F98 GB growth was seen on MRI 8–23 days post-inoculation (n = 15). RN lesions developed 6–8 months post-irradiation (n = 10). DCE-MRI was acquired using a fast low-angle shot (FLASH) sequence. Regions of interest (ROIs) encompassed peripheral contrast enhancement in GB (n = 15) and RN (n = 10) as well as central necrosis within these lesions (GB (n = 4), RN (n = 3)). Dynamic contrast-enhanced time series, obtained from the DCE-MRI data, were fitted to determine four function variables (amplitude A, offset from zero C, wash-in rate k, and wash-out rate D) as well as maximal intensity (Imax_F) and time to peak (TTP_F). Secondly, maps of semiquantitative and quantitative parameters (extended Tofts model) were created using Olea Sphere (_O). Semiquantitative DCE-MRI parameters included wash-in_O, wash-out_O, area under the curve (AUC_O), maximal intensity (Imax_O), and time to peak (TTP_O). Quantitative parameters included the rate constant plasma to extravascular-extracellular space (EES) (K _trans), the rate constant EES to plasma (K _ep), plasma volume (V _p), and EES volume (V _e). All (semi)quantitative parameters were compared between GB and RN using the Mann-Whitney U test. ROC analysis was performed.

Results

Wash-in rate (k) and wash-out rate (D) were significantly higher in GB compared to RN using curve fitting (p = 0.016 and p = 0.014). TTP_F and TTP_O were significantly lower in GB compared to RN (p = 0.001 and p = 0.005, respectively). The highest sensitivity (87 %) and specificity (80 %) were obtained for TTP_F by applying a threshold of 581 s. K _trans, K _ep, and V _e were not significantly different between GB and RN. A trend towards higher V _p values was found in GB compared to RN, indicating angiogenesis in GB (p = 0.075).

Conclusions

Based on our results, in a rat model of GB and RN, wash-in rate, wash-out rate, and the time to peak extracted from DCE-MRI time series data may be useful to discriminate GB from RN.

     

Predictive Value of Asphericity in Pretherapeutic [<Superscript>111</Superscript>In]DTPA-Octreotide SPECT/CT for Response to Peptide Receptor Radionuclide Therapy with [<Superscript>177</Superscript>Lu]DOTATATE

Purpose

The purpose of this study was to assess the value of the spatial heterogeneity of somatostatin receptor (SSR) volume, quantified as asphericity (ASP), and to predict response to peptide receptor radionuclide therapy (PRRT) in patients with metastatic gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN).

Procedures

From June 2011 to May 2013, patients suffering from GEP-NEN who underwent pretherapeutic [¹¹¹In-DTPA⁰]octreotide scintigraphy (Octreoscan®) prior to [¹⁷⁷Lu-DOTA⁰-Tyr³]octreotate ([¹⁷⁷Lu]DOTATATE)-PRRT were enrolled in this retrospective evaluation. SSR expression in 20 NEN patients was qualitatively and quantitatively assessed using the Krenning score, the metastasis to liver uptake ratio (M/L ratio), and ASP at baseline. Response to PRRT was evaluated based on lesions, which were classified as responding lesions (RL) and non-responding lesions (NRL) after 4- and 12-month follow-ups. The values of the Krenning score, M/L ratio, and ASP for response prediction were compared by using the Mann-Whitney U test, Kruskal-Wallis test, and receiver operating characteristic (ROC) curves.

Results

Seventy-seven metastases (liver, n = 40; lymph node, n = 24; bone, n = 11; pancreas, n = 2) showed SSR expression. A higher ASP level was significantly associated with poorer response at both time points. ROC analyses revealed the highest area under the curve (AUC) for discrimination between RL and NRL for ASP after 4 months (AUC 0.97; p = 0.019) and after 12 months (AUC 0.96; p < 0.001), followed by the Krenning score (AUC 0.74; p = 0.082 and AUC 0.85; p < 0.001, respectively) and M/L ratio (AUC 0.77; p = 0.107 and AUC 0.82; p < 0.001). The optimal cutoff value for ASP was 5.12 % (sensitivity, 90 %; specificity, 93 %).

Conclusion

Asphericity of SSR-expressing lesions in pretherapeutic single-photon emission computed tomography with integrated computed tomography (SPECT/CT) is a promising parameter for predicting response to PRRT in gastroenteropancreatic neuroendocrine neoplasms.

     

Computerised respiratory sounds can differentiate smokers and non-smokers

Cigarette smoking is often associated with the development of several respiratory diseases however, if diagnosed early, the changes in the lung tissue caused by smoking may be reversible. Computerised respiratory sounds have shown to be sensitive to detect changes within the lung tissue before any other measure, however it is unknown if it is able to detect changes in the lungs of healthy smokers. This study investigated the differences between computerised respiratory sounds of healthy smokers and non-smokers. Healthy smokers and non-smokers were recruited from a university campus. Respiratory sounds were recorded simultaneously at 6 chest locations (right and left anterior, lateral and posterior) using air-coupled electret microphones. Airflow (1.0–1.5 l/s) was recorded with a pneumotachograph. Breathing phases were detected using airflow signals and respiratory sounds with validated algorithms. Forty-four participants were enrolled: 18 smokers (mean age 26.2, SD = 7 years; mean FEV₁ % predicted 104.7, SD = 9) and 26 non-smokers (mean age 25.9, SD = 3.7 years; mean FEV₁ % predicted 96.8, SD = 20.2). Smokers presented significantly higher frequency at maximum sound intensity during inspiration [(M = 117, SD = 16.2 Hz vs. M = 106.4, SD = 21.6 Hz; t(43) = ?2.62, p = 0.0081, d _z  = 0.55)], lower expiratory sound intensities (maximum intensity: [(M = 48.2, SD = 3.8 dB vs. M = 50.9, SD = 3.2 dB; t(43) = 2.68, p = 0.001, d _z  = ?0.78)]; mean intensity: [(M = 31.2, SD = 3.6 dB vs. M = 33.7,SD = 3 dB; t(43) = 2.42, p = 0.001, d _z  = 0.75)] and higher number of inspiratory crackles (median [interquartile range] 2.2 [1.7–3.7] vs. 1.5 [1.2–2.2], p = 0.081, U = 110, r = ?0.41) than non-smokers. Significant differences between computerised respiratory sounds of smokers and non-smokers have been found. Changes in respiratory sounds are often the earliest sign of disease. Thus, computerised respiratory sounds might be a promising measure to early detect smoking related respiratory diseases.     

Potential Effect of Prolonged Sevoflurane Anesthesia on the Kinetics of [<Superscript>11</Superscript>C]Raclopride in Non-human Primates

Purpose

Positron emission tomography (PET) in non-human primates (NHP) is commonly performed under anesthesia, with sevoflurane being a widely used inhaled anesthetic. PET measurement in NHP can be repeated, and a difference in radioligand kinetics has previously been observed between the first and second PET measurement on the same day using sevoflurane anesthesia. In this study, we evaluated the effect of prolonged sevoflurane anesthesia on kinetics and binding potential (BP_ND) of [¹¹C]raclopride in NHP.

Procedures

Three cynomolgus monkeys underwent two to three PET measurements with [¹¹C]raclopride under continuous sevoflurane anesthesia on the same day. The concentration of sevoflurane was adjusted according to the general conditions and safety parameters of the NHP. Time to peak (TTP) radioactivity in the striatum was estimated from time-activity curves (TACs). The BP_ND in the striatum was calculated by the simplified reference tissue model using the cerebellum as reference region.

Results

In each NHP, the TTP became shorter in the later PET measurements than in the first one. Across all measurements (n = 8), concentration of sevoflurane correlated with TTP (Spearman’s ρ = ? 0.79, p = 0.03), but not with BP_ND (ρ = ? 0.25, p = 0.55).

Conclusions

These data suggest that sevoflurane affects the shape of TACs but has no evident effect on BP_ND in consecutive PET measurements.

     

Accuracy of simple approaches to assessing liver volume in radiological imaging

Objectives

The purpose of the study was to evaluate the accuracy of measured diameters and calculated volume indices for determining liver size and to derive a simple approach for estimating liver volume.

Methods

Three hundred twenty-nine volunteers (cohort A) were grouped according to liver volume: small (n = 109), medium (n = 110), and large (n = 110). True liver volume was determined by magnetic resonance imaging (MRI) using manual segmentation. Maximum diameters (maxdiam) of the liver and distances in midclavicular line (MCL) were measured. Volume indices were calculated as a simple product of the measured diameters. The calculated volume indices were calibrated to predict true liver volume. Performance of the calibrated method was evaluated in a control group (cohort B) including randomly selected volunteers (n = 110) and a patient group with histopathologically proven parenchymal liver diseases (n = 28).

Results

In cohort A, there was strong correlation between diameters and true liver volume (r _s = 0.631–0.823). Calculated volume indices had slightly better correlation (maxdiam r _s = 0.903, MCL r _s = 0.920). A calibration index was calculated from the volumes and diameters determined in cohort A. Application of this calibration on cohort B verified a very strong correlation between calibrated volume indices and true liver volume (maxdiam r _s = 0.920, MCL r _s = 0.909). In addition, the low mean difference between predicted liver volume (maxdiam = ?70.9 cm³;MCL = ?88.4 cm³) and true liver volume confirms that the calibrated method allows accurate assessment of liver volume.

Conclusions

Both simple diameters and volume indices allow estimating liver size. A simple calibration formula enables prediction of true liver volume without significant expense.

     

Stability of liver proton density fat fraction and changes in <Emphasis Type="Italic">R</Emphasis><Subscript>2</Subscript>* measurements induced by administering gadoxetic acid at 3T MRI

Objective

To assess changes in liver proton density fat fraction (PDFF) and R ₂* measurements in the presence of changes in tissue relaxation rates induced by administrating gadoxetic acid, using two different image reconstruction methods at 3T MRI.

Methods

Forty-five patients were imaged at 3T with chemical-shift-based MRI sequences before and 20 min after administration of gadoxetic acid. Image reconstructions were performed using hybrid and complex methods to obtain PDFF and R ₂* images. A single radiologist measured PDFF and R ₂* values on precontrast and postcontrast images. Precontrast and postcontrast PDFF values were compared using intraclass correlation coefficient (ICC), linear regression, and Bland–Altman analysis. Changes in R ₂* values from precontrast to postcontrast were correlated with relative liver enhancement (RLE) based on signal intensities on T ₁-weighted images using Spearman’s rank correlation.

Results

PDFF values were similar between precontrast and postcontrast images (ICC = 0.99, linear regression slopes = 0.98, mean difference = ?0.21 to ?0.31%). PDFF measurements were stable between precontrast and postcontrast images. Changes in R ₂* values were correlated with RLE (p < 0.001, r = 0.49–0.71).

Conclusions

PDFF measurements from both image reconstruction methods are stable in the presence of changes in tissue relaxation rates after administering gadoxetic acid at 3T MRI. Changes in R ₂* values correlate with established measures of gadoxetic acid uptake based on T ₁-weighted images.

     

Evaluation of [<Superscript>18</Superscript>F]CP18 as a Substrate-Based Apoptosis Imaging Agent for the Assessment of Early Treatment Response in Oncology

Purpose

The substrate-based positron emission tomography (PET) tracer [¹⁸F]CP18 is capable of detecting the activity of caspase-3/7, two key executioner proteases in the apoptosis pathway, through selective cleavage of the ligand by the activated proteases and subsequent accumulation in apoptotic cells. Using an in vitro and in vivo model of colorectal cancer (CRC), we investigated whether [¹⁸F]CP18 tracer accumulation provides a measure for apoptosis and reliably reflects early treatment response to chemotherapeutics.

Procedures

[¹⁸F]CP18 cell uptake was assessed in treated Colo205 cells (saline, 5-fluorouracil (5-FU), irinotecan or their combination) and correlated with caspase-3/7 activity. [¹⁸F]CP18 imaging was performed in Colo205 xenografts, starting with a baseline μPET/micro X-ray computed tomography (?μCT) scan, followed by a 3-day treatment with saline (n = 5), 5-FU (low sensitivity, n = 4), irinotecan (high sensitivity, n = 5), or a combination of both (n = 7). The study was concluded with a second [¹⁸F]CP18 scan, 24 h after final treatment administration, followed by tumor removal for gamma counting (%ID/g) and for cleaved caspase-3 immunohistochemistry (apoptotic index/necrosis). Tumors were delineated on μCT images and, using the obtained volumes of interest, average percentage injected dose per cubic centimeter (%ID/cm³) was calculated from every μPET image.

Results

In vitro, [¹⁸F]CP18 cell uptake was positively correlated with caspase-3/7 activity (r = 0.59, p = 0.003). A drug-dependent increase in [¹⁸F]CP18 tumor uptake compared to baseline was observed in animals treated with 5-FU (+14 ± 25 %), irinotecan (+56 ± 54 %), and their combination (+158 ± 69 %, p = 0.002). %ID/cm³ showed a positive relationship with both %ID/g (r = 0.83, p < 0.0001) and the apoptotic index (r = 0.60, p = 0.004), but not with tumor necrosis (r = 0.22, p = 0.36).

Conclusion

Both our in vitro and in vivo findings have shown the ability of [¹⁸F]CP18-PET to visualize therapy-induced cancer cell apoptosis and possibly serve as a biomarker for early therapy response.

     

Difficulties with Emotion Regulation and Psychopathology Interact to Predict Early Smoking Cessation Lapse

There is little knowledge about how emotion regulation difficulties interplay with psychopathology in terms of smoking cessation. Participants (n = 250; 53.2 % female, M _age  = 39.5, SD = 13.85) were community-recruited daily smokers (≥8 cigarettes per day) who self-reported motivation to quit smoking; 38.8 % of the sample met criteria for a current (past 12-month) psychological disorder. Emotion regulation deficits were assessed pre-quit using the Difficulties with Emotion Regulation Scale (DERS; Gratz and Roemer in J Psychopathol Behav Assess 26(1):41–54, 2004) and smoking behavior in the 28 days post-quit was assessed using the Timeline Follow-Back (TLFB; Sobell and Sobell in Measuring alcohol consumption: psychosocial and biochemical methods. Humana Press, Totowa, 1992). A Cox proportional-hazard regression analysis was used to model the effects of past-year psychopathology, DERS (total score), and their interaction, in terms of time to lapse post-quit day. After adjusting for the effects of gender, age, pre-quit level of nicotine dependence, and treatment condition, the model revealed a non-significant effect of past-year psychopathology (OR = 1.14, CI _95 % = 0.82–1.61) and difficulties with emotion regulation (OR = 1.01, CI _95 % = 1.00–1.01) on likelihood of lapse rate. However, the interactive effect of psychopathology status and difficulties with emotion regulation was significant (OR = 0.98, CI _95 % = 0.97–0.99). Specifically, there was a significant conditional effect of psychopathology status on lapse rate likelihood at low, but not high, levels of emotion regulation difficulties. Plots of the cumulative survival functions indicated that for smokers without a past-year psychological disorder, those with lower DERS scores relative to elevated DERS scores had significantly lower likelihood of early smoking lapse, whereas for smokers with past-year psychopathology, DERS scores did not differentially impact lapse rate likelihood. Smokers with emotion regulation difficulties may have challenges quitting, and not having such difficulties, especially without psychopathology, decreases the potential likelihood of early lapse.     

Quantification of Tumor Hypoxic Fractions Using Positron Emission Tomography with [<Superscript>18</Superscript>F]Fluoromisonidazole ([<Superscript>18</Superscript>F]FMISO) Kinetic Analysis and Invasive Oxygen Measurements

Purpose

The purpose of this study is to use dynamic [¹⁸F]fluoromisonidazole ([¹⁸F]FMISO) positron emission tomography (PET) to compare estimates of tumor hypoxic fractions (HFs) derived by tracer kinetic modeling, tissue-to-blood ratios (TBR), and independent oxygen (pO₂) measurements.

Procedures

BALB/c mice with EMT6 subcutaneous tumors were selected for PET imaging and invasive pO₂ measurements. Data from 120-min dynamic [¹⁸F]FMISO scans were fit to two-compartment irreversible three rate constant (K ₁, k ₂, k ₃) and Patlak models (K _i). Tumor HFs were calculated and compared using K _i, k ₃, TBR, and pO₂ values. The clinical impact of each method was evaluated on [¹⁸F]FMISO scans for three non-small cell lung cancer (NSCLC) radiotherapy patients.

Results

HFs defined by TBR (≥1.2, ≥1.3, and ≥1.4) ranged from 2 to 85 % of absolute tumor volume. HFs defined by K _i (>0.004 ml min cm^?3) and k ₃ (>0.008 min^?1) varied from 9 to 85 %. HF quantification was highly dependent on metric (TBR, k ₃, or K _i) and threshold. HFs quantified on human [¹⁸F]FMISO scans varied from 38 to 67, 0 to 14, and 0.1 to 27 %, for each patient, respectively, using TBR, k ₃, and K _i metrics.

Conclusions

[¹⁸F]FMISO PET imaging metric choice and threshold impacts hypoxia quantification reliability. Our results suggest that tracer kinetic modeling has the potential to improve hypoxia quantification clinically as it may provide a stronger correlation with direct pO₂ measurements.

     

A Randomized Trial Investigating the Pharmacokinetics,Pharmacodynamics, and Safety of Subcutaneous Semaglutide Once-Weekly in Healthy Male Japanese and Caucasian Subjects

Introduction

Semaglutide is a glucagon-like peptide-1 analogue for once-weekly subcutaneous treatment of type 2 diabetes. This trial compared the pharmacokinetics, pharmacodynamics, and safety of semaglutide in Japanese and Caucasian subjects.

Methods

In this single-center, double-blind, parallel-group, 13-week trial, 44 healthy male subjects (22 Japanese, 22 Caucasian) were randomized within each race to semaglutide 0.5 mg (n = 8), 1.0 mg (n = 8), placebo 0.5 mg (n = 3) or 1.0 mg (n = 3). The primary endpoint was semaglutide exposure at steady state [area under the curve (AUC_0–168h)].

Results

Steady-state exposure of semaglutide was similar for both populations: AUC_0–168h estimated race ratio (ERR), Japanese/Caucasian: 0.5 mg, 1.06; 1.0 mg, 0.99; maximum concentration (C_max) ERR: 0.5 mg, 1.06; 1.0 mg, 1.02. Exposure after the first dose (0.25 mg) was slightly higher in Japanese versus Caucasian subjects (AUC_0–168h ERR 1.11; C_max ERR 1.14). Dose-dependent increases in AUC_0–168h and C_max occurred in both populations. Accumulation was as expected, based on the half-life (t_1/2, ~ 1 week) and dosing interval of semaglutide. Significant body weight reductions were observed with semaglutide 0.5 mg and 1.0 mg in Japanese (both p ≤ 0.05) and Caucasian (both p ≤ 0.05) subjects versus placebo. No new safety issues were identified.

Conclusions

The pharmacokinetic, pharmacodynamic, and safety profiles of semaglutide were similar in Japanese and Caucasian subjects, suggesting that no dose adjustment is required for the clinical use of semaglutide in Japanese subjects.

Funding

Novo Nordisk A/S, Denmark.

Trial registration

ClinicalTrials.gov identifier NCT02146079. Japanese trial registration number JapicCTI-142550.

     

Antifeedant and Insecticidal Activity of Plant Extracts Against <Emphasis Type="Italic">Spodoptera litura</Emphasis> (Fab.) and <Emphasis Type="Italic">Lipaphis erysimi</Emphasis>

The solvent extracts of four plants, viz. Polyalthia longifolia (Sonn.) Thw. (PL), Paederia foetida (PF), Limonia acidissima L. (LA) and Balanites aegyptiaca (L.) Del. (BA), from different families, were screened for their antifeedant, insecticidal and insect growth regulatory potential against important crop pests. The solvent extracts, namely methanol, petroleum ether, chloroform and water, of all four plants were tested for their bio-activity against lepidopteran insect pest, Spodoptera litura; and sucking insect pest, L. erysimi (mustard aphid). It was observed that Polyalthia longifolia (methanol extract) exhibited maximum potency with least concentration of 0.1 % (~1080 ppm) to give 50 % antifeedancy, followed by P. longifolia (petroleum ether) with a value of 0.2 % (~2360 ppm) and Limonia acidissima (methanol) and L. acidissima (petroleum ether). The least active compound for antifeedancy was found in the aqueous extract of Balanites aegyptica. Out of 16 plant extracts bio-assayed, methanol showed potential antifeedancy when compared with chloroform, water and petroleum ether extracts. But chloroform and petroleum ether extracts of all four plants gave very promising insecticidal activity against aphids, in comparison to other two extracts. L. acidissima (water), B. aegyptica (methanol), P. longifolia (methanol) and P. foetida (water) did not give any insecticidal activity with 50 % lethal concentration (LC₅₀) up to 0.1 % as maximum concentration.     

Transcutaneous P<Emphasis Type="SmallCaps">tc</Emphasis>CO<Subscript>2</Subscript> measurement in combination with arterial blood gas analysis provides superior accuracy and reliability in ICU patients

Hyper or hypoventilation may have serious clinical consequences in critically ill patients and should be generally avoided, especially in neurosurgical patients. Therefore, monitoring of carbon dioxide partial pressure by intermittent arterial blood gas analysis (PaCO₂) has become standard in intensive care units (ICUs). However, several additional methods are available to determine PCO₂ including end-tidal (PetCO₂) and transcutaneous (PtcCO₂) measurements. The aim of this study was to compare the accuracy and reliability of different methods to determine PCO₂ in mechanically ventilated patients on ICU. After approval of the local ethics committee PCO₂ was determined in n = 32 ICU consecutive patients requiring mechanical ventilation: (1) arterial PaCO₂ blood gas analysis with Radiometer ABL 625 (ABL; gold standard), (2) arterial PaCO₂ analysis with Immediate Response Mobile Analyzer (IRMA), (3) end-tidal PetCO₂ by a Propaq 106 EL monitor and (4) transcutaneous PtcCO₂ determination by a Tina TCM4. Bland–Altman method was used for statistical analysis; p < 0.05 was considered statistically significant. Statistical analysis revealed good correlation between PaCO₂ by IRMA and ABL (R² = 0.766; p < 0.01) as well as between PtcCO₂ and ABL (R² = 0.619; p < 0.01), whereas correlation between PetCO₂ and ABL was weaker (R² = 0.405; p < 0.01). Bland–Altman analysis revealed a bias and precision of 2.0 ± 3.7 mmHg for the IRMA, 2.2 ± 5.7 mmHg for transcutaneous, and ?5.5 ± 5.6 mmHg for end-tidal measurement. Arterial CO₂ partial pressure by IRMA (PaCO₂) and PtcCO₂ provided greater accuracy compared to the reference measurement (ABL) than the end-tidal CO₂ measurements in critically ill in mechanically ventilated patients patients.     

Acute respiratory distress syndrome mimickers lacking common risk factors of the Berlin definition

Purpose

Some patients presenting with acute respiratory failure and meeting the Berlin criteria for acute respiratory distress syndrome (ARDS) lack exposure to common risk factors (CRF). These so-called ARDS mimickers often lack histological diffuse alveolar damage. We aimed to describe such ARDS mimickers lacking CRF (ARDS_CRF?) in comparison with others (ARDS_CRF+).

Methods

Retrospective study including all patients receiving invasive mechanical ventilation for ARDS admitted to the intensive care units (ICUs) of two tertiary care centers from January 2003 to December 2012.

Results

The prevalence of ARDS_CRF? was 7.5 % (95 % CI [5.5–9.5]; n = 50/665). On the basis of medical history, bronchoalveolar lavage fluid cytology, and chest CT scan patterns, four etiological categories were identified: immune (n = 18; 36 %), drug-induced (n = 13; 26 %), malignant (n = 7; 14 %), and idiopathic (n = 12; 24 %). Although the ARDS_CRF? patients had a lower logistic organ dysfunction score (4 [3–8] vs. 10 [6–13]; p < 0.0001) and less often shock upon ICU admission (44 vs. 80 %; p < 0.0001) than their counterparts, their overall ICU mortality rate was very high (66 % [46–74]), and the absence of CRF remained associated with ICU mortality by multivariable logistic regression analysis (adjusted OR = 2.06; 95 % CI [1.02–4.18]; p = 0.044). Among ARDS_CRF? patients, the presence of potentially reversible lung lesions with corticosteroids (aOR = 0.14; 95 % CI [0.03–0.62]) was associated with ICU survival.

Conclusions

The absence of CRF among patients with ARDS is common and associated with a higher risk of mortality. For such atypical ARDS, a complete diagnostic workup, including bronchoalveolar lavage fluid cytology and chest CT scan patterns, should be performed to identify those patients who might benefit from specific therapies, including corticosteroids.

     

Parametric Imaging of [<Superscript>11</Superscript>C]Flumazenil Binding in the Rat Brain

Purpose

This study evaluates the performance of several parametric methods for assessing [¹¹C]flumazenil binding distribution in the rat brain.

Procedures

Dynamic (60 min) positron emission tomography data with metabolite-corrected plasma input function were retrospectively analyzed (male Wistar rats, n = 10). Distribution volume (V _T) images were generated from basis function method (BFM), Logan graphical analysis (Logan), and spectral analysis (SA). Using the pons as pseudo-reference tissue, binding potential (BP _ND and DVR–1) images were obtained from receptor parametric imaging algorithms (RPM and SRTM2) and reference Logan (RLogan). Standardized uptake value images (SUV and SUVR) were also computed for different intervals post-injection. Next, regional averages were extracted from the parametric images, using pre-defined volumes of interest, which were also applied to the regional time-activity curves from the dynamic data. Parametric data were compared to their regional counterparts and to two-tissue compartment model (2TCM)-based values (previously defined as the model of choice for rats). Parameter agreement was assessed by linear regression analysis and Bland-Altman plots.

Results

All parametric methods strongly correlated to their regional counterparts (R ² > 0.97) and to the 2TCM values (R ² ≥ 0.95). SA and RLogan underestimated V _T and BP _ND (slope of 0.93 and 0.86, respectively), while SUVR-1 overestimated BP _ND (slope higher than 1.07 for all intervals). While BFM and SRTM2 had the smallest bias to 2TCM values (0.05 for both), ratio Bland-Altman plots showed Logan and RLogan displayed relative errors which were comparable between different regions, in contrast with the other methods. Although SUV consistently underestimated V _T, the bias in this method was also constant across regions.

Conclusions

All parametric methods performed well for the analysis of [¹¹C]flumazenil distribution and binding in the rat brain. However, Logan and RLogan slightly outperformed the other methods in terms of precision, providing robust parameter estimation and constant bias. Yet, other methods can be of interest, because they can provide tissue perfusion (i.e., K ₁ with BFM and SA), relative flow (i.e., R ₁ with RPM and SRTM2), and model order (SA) images.

     

Superselective transcatheter arterial embolization in patients with acute peripancreatic bleeding complications: review of 44 cases

Purpose

To evaluate the efficacy of superselective transcatheter arterial embolization (TAE) in the treatment of acute peripancreatic bleeding complications.

Methods

During a 9-year period, 44 patients with acute bleeding of the peripancreatic arteries underwent TAE in our institution. Thirty-eight patients were treated using microcatheters and 6 patients with a diagnostic catheter. Embolic agents included coils (n = 38), polyvinyl alcohol (PVA) particles (n = 2), isobutyl cyanoacrylate (n = 2), coils plus PVA particles (n = 1), and coils plus isobutyl cyanoacrylate (n = 1). Outcome measures included technical success, clinical success, and the rate of complications.

Results

Identified bleeding sources included gastroduodenal artery (n = 14), splenic artery (n = 9), pancreaticoduodenal artery (n = 6), common hepatic artery (n = 5), superior mesenteric artery branches (n = 4), proper hepatic artery (n = 3), and dorsal/transverse pancreatic artery (n = 3). Technical success with effective control of active bleeding was achieved in 41/44 patients (93 %). Clinical success attributed to TAE alone was documented in 40/44 patients (91 %). The rate of major complications was 2 % including death in one patient.

Conclusions

Superselective TAE allows effective, minimally invasive control of acute peripancreatic bleeding complications with a low rate of therapeutically relevant complications.

     

Assessment of aortic stiffness among patients with systemic lupus erythematosus and rheumatoid arthritis by magnetic resonance imaging

To evaluate aortic stiffness by MRI in female patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) in comparison to controls. We measured aortic strain, distensibility and pulse wave velocity (PWV) by MRI in 30 SLE patients, 31 RA patients and 53 matched controls. Mean PWV in SLE and RA patients were higher in comparison to controls (9.2 ± 4.4 vs. 7.6 ± 3.0 m/s, p = 0.04) and (6.2 ± 2.3 vs. 5.4 ± 1.7, p = 0.04) respectively. Aortic distensibility among RA patients was significantly lower in comparison to controls (4.4 ± 4.6 vs. 5.8 ± 4.9 kPa^?1 × 10^?3, p = 0.04). A significant correlation was found between PWV and age (r = 0.67, p < 0.001), Framingham risk score (r = 0.61, p < 0.001), waist to hip ratio (r = 0.45, p < 0.001), systolic blood pressure (r = 0.37, p = 0.01), diabetes (r = 0.32, p = 0.001) and dyslipidemia (r = 0.32, p = 0.001). In multivariate analysis for the prediction of PWV, variables which were found significant included: RA (p = 0.01), age (p < 0.001) and hypertension (p = 0.01) for patients with RA and SLE (p = 0.02), waist to hip ratio (p < 0.001) and total cholesterol (p < 0.001) for patients with SLE. Arterial stiffness, characterized by metrics of aortic distensibility and pulse wave velocity derived from MRI, is increased in SLE and RA female patients.     

Vascular ultrasound in pediatrics: utility and application of location and measurement of jugular and femoral vessels

Objective

To measure the depth (D _p) and diameter (D _m) of the internal jugular vein (IJV), femoral vein (FV), and femoral artery (FA) in pediatric patients to evaluate the clinical implications.

Methods

This study included 125 pediatric patients. All of them underwent bilateral ultrasound study of vessels and were classified into three groups based on anthropometric and demographic parameters.

Results

Measured mean D _p values were: 0.72 (0.34) cm for the FA, 0.79 (0.35) cm for the FV, and 0.77 (0.24) cm for the IJV. Mean antero-posterior D _m values were: 0.37 (0.17) cm for the FA, 0.42 (0.22) cm for the FV, and 0.59 (0.23) cm for the IJV. D _p and D _m increased with age (A), weight (W), height (H), and body surface area (BSA). In the lower ranges of these variables, D _p was similar for all three studied vessels (0.6–0.7 cm). In the higher ranges, femoral vessel D _p values (1.1–1.2 cm) were larger than jugular ones (0.9 cm). Additionally, in these low ranges, IJV D _m values were larger than femoral ones (0.45–0.50 vs. 0.25 cm). In the higher ranges, diameter values were similar (0.6–0.7 cm).

Conclusions

In pediatric patients, major vessels can be located and their depth and diameter measured by vascular ultrasound. In younger patients, jugular and femoral vessels had similar depth values; in older ones, they had similar diameters. Ultrasound measurements in pediatric patients could facilitate the choice of the vessel to be cannulated, the catheter diameter, and the length of the needle to be used. Vascular canalization of IJV may be recommended as the first choice because of its low depth and large diameter.

     

Complementary and Alternative Medicine Treatments for Generalized Anxiety Disorder: Systematic Review and Meta-analysis of Randomized Controlled Trials

Introduction

The objective was to evaluate efficacy/safety of complementary and alternative medicine (CAM) methods for generalized anxiety disorder (GAD) based on randomized controlled trials in adults.

Methods

Data sources. Six electronic databases (“generalized anxiety (disorder)” and “randomized trial”) and reference lists of identified publications were searched to March 2017. Study selection. Eligibility: full-text publications (English, German language); CAM versus conventional treatment, placebo/sham or no treatment; GAD diagnosed according to standard criteria; and a validated scale for disease severity. Of the 6693 screened records, 32 were included (18 on biologically-based therapies, exclusively herbal preparations; eight on manipulative and body-based therapies; and three on alternative medical systems and three on mind–body therapies). Data extraction. Cochrane Collaboration methodology was used for quality assessment and data extraction.

Results

Direct comparisons of Kava Kava (Piper methysticum) extracts to placebo (4 quality trials, n = 233) were highly heterogeneous. Network meta-regression reduced heterogeneity and suggested a modest Kava effect [end-of-treatment Hamilton Anxiety scale score difference adjusted for baseline scores and trial duration: ? 3.24 (95% CI ? 6.65, 0.17; P = 0.059), Kava Kava 4 arms, n = 139; placebo 5 arms, n = 359]. Lavender (Lavandula angustifolia) extract (1 quality trial, 10 weeks, n = 523) and a combination of extracts of C. oxycantha, E. californica and magnesium (1 quality trial, 12 weeks, n = 264) were superior to placebo and balneotherapy was superior to paroxetine (1 quality trial, 8 weeks, n = 237) indicating efficacy. All other trials were small and/or of modest/low quality and/or lacked assay sensitivity. Safety reporting was poor.

Conclusion

Evidence about efficacy/safety of most CAM methods in GAD is limited. Apparent efficacy of certain herbal preparations and body-based therapies requires further confirmation.

     

Effect of In situ Recycling of Sugarcane Crop Residues on Soil Enzyme Activities Under Soybean–Maize System

An investigation was carried out by conducting a field experiment at the farm of the Mahatma Phule Krishi Vidyapeeth (MPKV), Rahuri. The significant grain yield of soybean (37.5 q ha^?1) and maize (49 q ha^?1) were observed in the treatment receiving 100 % recommended doses of Nitrogen, Phosphorus and Potassium (NPK) + in situ compost of crop residues, pressmud compost (T₆). After harvest of maize dehydrogenase activity, acid phosphatase, β-glucosidase and urease were significantly improved in T₇ treatment as compared to other treatments. However, fluorescein diacetate activity and alkaline phosphatase were significantly greater in T₆ treatment in post-harvest soil samples of maize. In the post-harvest soil of maize the bacterial and actinomycetes population were greater in the treatment receiving in situ decomposition of sugarcane crop residues + 100 % recommended dose of NPK (T₃). The fungal population after harvest of maize was found maximum in treatment T₇. The total organic carbon was significantly correlated with dehydrogenase (r = 0.65, P < 0.01), fluorescein diacetate (r = 0.71, P < 0.01), acid phosphatase (r = 0.66, P < 0.01), β-glucosidase (r = 0.65, P < 0.01), and urease (r = 0.57, P < 0.01). There was a significant correlation (r = 0.77, P < 0.01) between TOC and soybean yield, and between total organic carbon and maize yield (r = 0.98, P < 0.01). The result suggest that in situ recycling of sugarcane crop residues and the industrial wastes with suitable interventions like use of bioinoculum, phosphatic fertilizer and urea may help for improving better crop productivity and soil biological activities.