Prospective external validation of IOTA methods for classifying adnexal masses and retrospective assessment of two-step strategy using benign descriptors and ADNEX model: Portuguese multicenter study.

OBJECTIVES: To externally and prospectively validate the International Ovarian Tumor Analysis (IOTA) Simple Rules (SRs), Logistic Regression model 2 (LR2) and Assessment of Different NEoplasias in the adneXa (ADNEX) model in a Portuguese population, comparing these approaches with subjective assessment and the risk-of-malignancy index (RMI), as well as with each other. This study also aimed to retrospectively validate the IOTA two-step strategy, using modified benign simple descriptors (MBDs) followed by the ADNEX model in cases in which MBDs were not applicable. METHODS: This was a prospective multicenter diagnostic accuracy study conducted between January 2016 and December 2021 of consecutive patients with an ultrasound diagnosis of at least one adnexal tumor, who underwent surgery at one of three tertiary referral centers in Lisbon, Portugal. All ultrasound assessments were performed by Level-II or -III sonologists with IOTA certification. Patient clinical data and serum CA 125 levels were collected from hospital databases. Each adnexal mass was classified as benign or malignant using subjective assessment, RMI, IOTA SRs, LR2 and the ADNEX model (with and without CA 125). The reference standard was histopathological diagnosis. In the second phase, all adnexal tumors were classified retrospectively using the two-step strategy (MBDs + ADNEX). Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios and overall accuracy were determined for all methods. Receiver-operating-characteristics curves were constructed and corresponding areas under the curve (AUC) were determined for RMI, LR2, the ADNEX model and the two-step strategy. The ADNEX model calibration plots were constructed using locally estimated scatterplot smoothing (LOESS). RESULTS: Of the 571 patients included in the study, 428 had benign disease and 143 had malignant disease (prevalence of malignancy, 25.0%), of which 42 had borderline ovarian tumor, 93 had primary invasive adnexal cancer and eight had metastatic tumors in the adnexa. Subjective assessment had an overall sensitivity of 97.9% and a specificity of 83.6% for distinguishing between benign and malignant lesions. RMI showed high specificity (95.6%) but very low sensitivity (58.7%), with an AUC of 0.913. The IOTA SRs were applicable in 80.0% of patients, with a sensitivity of 94.8% and specificity of 98.6%. The IOTA LR2 had a sensitivity of 84.6%, specificity of 86.9% and an AUC of 0.939, at a malignancy risk cut-off of 10%. At the same cut-off, the sensitivity, specificity and AUC for the ADNEX model with vs without CA 125 were 95.8% vs 98.6%, 82.5% vs 79.7% and 0.962 vs 0.960, respectively. The ADNEX model gave heterogeneous results for distinguishing between benign masses and different subtypes of malignancy, with the highest AUC (0.991) for discriminating benign masses from primary invasive adnexal cancer Stages II-IV, and the lowest AUC (0.696) for discriminating primary invasive adnexal cancer Stage I from metastatic lesion in the adnexa. The calibration plot suggested underestimation of the risk by the ADNEX model compared with the observed proportion of malignancy. The MBDs were applicable in 26.3% (150/571) of cases, of which none was malignant. The two-step strategy using the ADNEX model in the second step only, with and without CA 125, had AUCs of 0.964 and 0.961, respectively, which was similar to applying the ADNEX model in all patients. CONCLUSIONS: The IOTA methods showed good-to-excellent performance in the Portuguese population, outperforming RMI. The ADNEX model was superior to other methods in terms of accuracy, but interpretation of its ability to distinguish between malignant subtypes was limited by sample size and large differences in the prevalence of tumor subtypes. The IOTA MBDs are reliable in identifying benign disease. The two-step strategy comprising application of MBDs followed by the ADNEX model if MBDs are not applicable, is suitable for daily clinical practice, circumventing the need to calculate the risk of malignancy in all patients. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Cell surface targeting of the Melanocortin 5 Receptor (MC5R) requires serine-rich terminal motifs.

The Melanocortin 5 Receptor (MC5R) is a cell surface receptor that belongs to the class of G-protein coupled receptors (GPCRs), which comprises an intracellular carboxylic domain, seven transmembrane helices and an extracellular amino terminal. Over the last few years, MC5R has been implicated in the regulation of lipid metabolism in exocrine glands, muscle and even in adipose tissue and its function is quite dependent on its correct cell membrane targeting. In this context, the purpose of this work was to study the role of MC5R N-terminus in the receptor trafficking from the endoplasmic reticulum (ER) through the Golgi complex to the plasma membrane. Analysis of N-terminal deleted forms of MC5R revealed that the first 21 amino acids contain the information responsible for the receptor cell surface expression and the removal of further amino acids interfere with the receptor synthesis. In this setting, several mutant forms of the receptor were created by site directed mutagenesis of the MC5R first 21 amino acids and their presence at the plasma membrane was assessed. We have found that two small motifs, constituted by residues Ser4/Ser5 and Ser17/Glu18, are clearly involved in the correct targeting of MC5R to the cell surface. Fluorescence microscopy analysis has revealed that MC5R constructs with mutations in those residues are mainly retained at the ER/Golgi complex. Furthermore, the homodimerization ability of the receptor is maintained in these mutant forms, suggesting that other mechanisms are involved in the regulation of the anterograde transport of MC5R by those N-terminal domains.

In vitro activity of zoliflodacin (ETX0914) against macrolide-resistant, fluoroquinolone-resistant and antimicrobial-susceptible Mycoplasma genitalium strains.

Background: Mycoplasma genitalium is estimated to be the second most common cause of bacterial sexually transmitted infection in Europe. It is of increasing public health concern due to the rapid development of resistance to different antimicrobial classes, including the preferred first- and second-line treatments azithromycin and moxifloxacin. Thus, new antimicrobial agents are urgently needed, especially for the treatment of MDR strains. Methods: The in vitro activity of the new spiropyrimidinetrione zoliflodacin against 47 M. genitalium strains was assessed by growing M. genitalium in Vero cell culture and measuring growth by quantitative PCR. The collection included 34 moxifloxacin-susceptible (MIC <1 mg/L) and 13 moxifloxacin-resistant (MIC ≥1 mg/L) strains. Twenty-three of the strains were azithromycin resistant (MIC ≥16 mg/L) and 12 of these strains were MDR. Results: Only one (2.1%) strain with substantially increased MIC (4 mg/L) and potential resistance to zoliflodacin was found. Zoliflodacin was overall more potent than moxifloxacin (P = 0.009) and no cross-resistance was observed between the two drug classes of topoisomerase II inhibitors. Differences in the MICs of zoliflodacin and azithromycin were not statistically significant; however, 23 (48.9%) compared with potentially 1 (2.1%) of the strains were resistant to azithromycin and zoliflodacin, respectively. Conclusions: Zoliflodacin is a promising candidate for the treatment of M. genitalium and it is important to further develop and evaluate this drug.

ZnWO4 nanocrystals: synthesis, morphology, photoluminescence and photocatalytic properties.

The present joint experimental and theoretical work provides in-depth understanding on the morphology and structural, electronic, and optical properties of ZnWO4 nanocrystals. Monoclinic ZnWO4 nanocrystals were prepared at three different temperatures (140, 150, and 160 °C) by a microwave hydrothermal method. Then, the samples were investigated by X-ray diffraction with Rietveld refinement analysis, field-emission scanning electron microscopy, transmission electronic microscopy, micro-Raman and Fourier transform infrared spectroscopy, ultraviolet-visible spectroscopy, and photoluminescence measurements. First-principles theoretical calculations within the framework of density functional theory were employed to provide information at the atomic level. The band structure diagram, density of states, Raman and infrared spectra were calculated to understand the effect of structural order-disorder on the properties of ZnWO4. The effects of the synthesis temperature on the above properties were rationalized. The band structure revealed direct allowed transitions between the VB and CB and the experimental results in the ultraviolet-visible region were consistent with the theoretical results. Moreover, the surface calculations allowed the association of the surface energy stabilization with the temperature used in the synthesis of the ZnWO4 nanocrystals. The photoluminescence properties of the ZnWO4 nanocrystals prepared at 140, 150, and 160 °C were attributed to oxygen vacancies in the [WO6] and [ZnO6] clusters, causing a red shift of the spectra. The ZnWO4 nanocrystals obtained at 160 °C exhibited excellent photodegradation of Rhodamine under ultraviolet light irradiation, which was found to be related to the surface energy and the types of clusters formed on the surface of the catalyst.

Obesity promotes prolonged ovalbumin-induced airway inflammation modulating T helper type 1 (Th1), Th2 and Th17 immune responses in BALB/c mice.

Clinical and epidemiological studies indicate that obesity affects the development and phenotype of asthma by inducing inflammatory mechanisms in addition to eosinophilic inflammation. The aim of this study was to assess the effect of obesity on allergic airway inflammation and T helper type 2 (Th2) immune responses using an experimental model of asthma in BALB/c mice. Mice fed a high-fat diet (HFD) for 10 weeks were sensitized and challenged with ovalbumin (OVA), and analyses were performed at 24 and 48 h after the last OVA challenge. Obesity induced an increase of inducible nitric oxide synthase (iNOS)-expressing macrophages and neutrophils which peaked at 48 h after the last OVA challenge, and was associated with higher levels of interleukin (IL)-4, IL-9, IL-17A, leptin and interferon (IFN)-γ in the lungs. Higher goblet cell hyperplasia was associated with elevated mast cell influx into the lungs and trachea in the obese allergic mice. In contrast, early eosinophil influx and lower levels of IL-25, thymic stromal lymphopoietin (TSLP), CCL11 and OVA-specific immunoglobulin (IgE) were observed in the obese allergic mice in comparison to non-obese allergic mice. Moreover, obese mice showed higher numbers of mast cells regardless of OVA challenge. These results indicate that obesity affects allergic airway inflammation through mechanisms involving mast cell influx and the release of TSLP and IL-25, which favoured a delayed immune response with an exacerbated Th1, Th2 and Th17 profile. In this scenario, an intense mixed inflammatory granulocyte influx, classically activated macrophage accumulation and intense mucus production may contribute to a refractory therapeutic response and exacerbate asthma severity.

Enhanced expression of PD-L1 and IFN-γ on dendritic cells is associated with BCG-induced Th2 inhibition.

Accumulating evidence indicates that the exposure to Mycobacterium bovis bacillus Calmette-Guérin (BCG) prevents the development of allergy and the airway dendritic cells (DCs) may be involved in this protective effect. However, studies to better characterize the specific interactions between BCG and DCs and their role in this mycobacteria-mediated Th2 cell suppression are still ongoing. This study aimed to evaluate the effect of the neonatal BCG vaccination in the innate immune response in a mouse model of ovalbumin (OVA)-induced airway inflammation. BCG treated neonatal BALB/c mice were sensitized and challenged with aerosolized OVA. Twenty-four hours after the last challenge, samples were collected for analysis. The intranasal BCG treatment inhibited the allergic Th2-response by decreasing the allergen-induced eosinophilic inflammation, EPO activity, CCL11, IL-25, TSLP, IL-4 and IL-5 lung levels, and serum levels of IgE. Mycobacteria treatment increased lung levels of IL-10 and TGF-ß, and the TLR2 and TLR4 expressions by pulmonary CD11c+CD103+CD8α+ DCs. Additionally an enhanced expression of PD-L1 was observed besides an increased production of IFN-γ by these cells. These results indicated that neonatal BCG vaccination inhibits key features of allergic airway inflammation, probably by promoting T regulatory immune response via an enhanced expression of TLR2, TLR4 and PD-L1 on DCs.

Cognitive impairment and magnetic resonance imaging correlates in primary progressive multiple sclerosis.

OBJECTIVES: To characterize cognitive impairment in primary progressive multiple sclerosis (PPMS) and to correlate the pattern of cognitive deficits with brain magnetic resonance imaging (MRI) volumetric data. MATERIALS AND METHODS: In a multicenter cross-sectional study, we recruited consecutive patients with PPMS as well as age, sex, and education level-matched healthy controls (HC). All participants underwent neuropsychological (NP) assessment, and brain MRI was performed in patients with PPMS for analysis of lesion load, subcortical GM volumes, and regional cortical volumes. RESULTS: We recruited 55 patients with PPMS and 36 HC. Thirty-six patients were included in the MRI analysis. Patients with PPMS performed significantly worse than HC in all NP tests. Subcortical GM volume was significantly correlated with all NP tests, except for Stroop Test, with the largest effect for the thalamus (r=-.516 [BVMT-R DR, P=.016 FDR-corrected] to r=.664 [SDMT, P<.001 FDR-corrected]). In the stepwise linear regression model, thalamic volume was the only predictor of performance in all NP tests. CONCLUSION: Cognitive impairment is common in PPMS and affects all evaluated cognitive domains. Subcortical GM volume, particularly of the thalamus, is a strong predictor of cognitive performance, suggesting it has a central role in the pathophysiology of PPMS-related cognitive dysfunction.

Age-related expression of TGF beta family receptors in human cumulus oophorus cells.

PURPOSE: During ovarian follicle growth, local cellular interactions are essential for oocyte quality acquisition and successful fertilization. While cumulus cells (CCs) nurture oocytes, they also deliver oocyte-secreted factors (OSFs) that activate receptors on CCs. We hypothesized that disturbance of those interactions contributes to age-related lower reproductive success in women submitted to assisted reproductive technology treatments. METHODS: Women aged 27-48, without recognized personal reproductive disorder, were enrolled in the study and divided in <35- and ≥35-year-old groups. CCs collected upon follicle aspiration were processed for immunocytochemistry and RNA extraction. The expression patterns of OSF receptors BMPR2, ALK 4, ALK5, and activin receptor-like kinase (ALK6) were studied. RESULTS: Independently of age, receptors were found mostly in the cell periphery. The quantitative assay revealed that in older women, BMPR2, ALK 4, and ALK6 were all significantly decreased, whereas ALK5 was slightly increased. CONCLUSIONS: Female age imparts an effect on the expression of OSF receptors in CCs. The findings indicate that reproductive aging affects the local regulation of signaling pathways mediated by BMPR2, ALK6, and ALK4 receptor activation, suggesting their joint involvement.

The role of targeted BRCA1/BRCA2 mutation analysis in hereditary breast/ovarian cancer families of Portuguese ancestry.

We report the analysis of altogether 1050 suspected hereditary breast/ovarian cancer (HBOC) families, 524 fully screened for BRCA1/BRCA2 mutations and 526 tested only for the most common mutations. Of the 119 families with pathogenic mutations, 40 (33.6%) had the BRCA2 c.156_157insAlu rearrangement and 15 (12.6%) the BRCA1 c.3331_3334del mutation, the former being specific of Portuguese ancestry and the latter showing a founder effect in Portugal. Interestingly, the two most common mutations were found in a significant proportion of the HBOC families with an a priori BRCAPRO mutation probability <10%. We recommend that all suspected HBOC families from Portugal or with Portuguese ancestry, even those fulfilling moderately stringent clinical-criteria for genetic testing, should be specifically analyzed for the two most common BRCA1/BRCA2 founder mutations, and we here present a simple method for this first tier test. Screening of the entire coding regions of BRCA1 and BRCA2 should subsequently be offered to those families with a mutation probability ≥10% if none of those founder mutations are found.

Experimental and theoretical investigations of electronic structure and photoluminescence properties of ß-Ag2MoO4 microcrystals.

In this paper, we investigate a correlation between theoretical calculations and experimental data to explain the electronic structure and optical properties of silver molybdate (ß-Ag2MoO4) microcrystals synthesized by the microwave-assisted hydrothermal method. X-ray diffraction, Rietveld refinement, and micro-Raman spectroscopy confirmed that these microcrystals crystallize in a spinel-type cubic structure. Field-emission scanning electron microscopy images revealed that the processing temperatures influence in the final shape of microcrystals. Optical properties were analyzed by ultraviolet-visible diffuse reflectance spectroscopy; the increase in the optical band gap energy (Egap) (from 3.24 to 3.31 eV) with processing temperature is associated with the reduction of intermediary energy levels. First-principles quantum mechanical calculations based on the density functional theory at the B3LYP level were conducted. The calculated band structure revealed an indirect Egap of approximately 4.00 and 3.34 eV for the ß-Ag2MoO4 without and with the formation of defects, respectively. Theoretical calculations based on density of states and electron density maps were employed to understand the polarization phenomenon induced by structural defects in the ß-Ag2MoO4 crystals. Finally, photoluminescence properties at room temperature of ß-Ag2MoO4 microcrystals were explained by the charge-transfer mechanism involving tetrahedral [MoO4] clusters.

Herpes simplex virus and cytomegalovirus co-infection presenting as exuberant genital ulcer in a woman infected with human immunodeficiency virus.

In patients infected with human immunodeficiency virus (HIV), genital herpes can result in severe and atypical clinical presentations, and can become resistant to aciclovir treatment. Rarely, these manifestations may represent concurrent herpes simplex virus (HSV) with other agents. We report a 41-year-old black woman with HIV who presented with extensive and painful ulceration of the genitalia. Histological examination of a biopsy sample was suggestive of herpetic infection, and intravenous aciclovir was started, but produced only partial improvement. PCR was performed on the biopsy sample, and both HSV and cytomegalovirus (CMV) DNA was detected. Oral valganciclovir was started with therapeutic success. CMV infection is common in patients infected with HIV, but its presence in mucocutaneous lesions is rarely reported. This case exemplifies the difficulties of diagnosis of genital ulcers in patients infected with HIV. The presence of exuberant and persistent HSV genital ulcers in patients with HIV should also raise suspicions of the presence of co-infection with other organisms such as CMV.

A Meta-analysis of the Efficacy and Safety of Stereotactic Arrhythmia Radioablation (STAR) in Patients with Refractory Ventricular Tachycardia.

AIMS: Reports of stereotactic arrhythmia radioablation (STAR) in patients with refractory ventricular tachycardia after catheter ablation are limited to small series. Here, we carried out a systematic review and meta-analysis of studies to better determine the efficacy and toxicity of STAR for ventricular tachycardia. MATERIALS AND METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) and the Meta-analyses Of Observational Studies in Epidemiology (MOOSE) guidelines, eligible studies were identified on Medline, Embase, Cochrane Library and the proceedings of annual meetings to 10 February 2023. Efficacy was defined as a ventricular tachycardia burden reduction >70% at 6 months; safety was defined as <10% of any grade ≥3 toxicity. RESULTS: Seven observational studies with a total of 61 patients treated were included. At 6 months, the ventricular tachycardia burden reduction was 92% (95% confidence interval 85-100%) and use of fewer than two anti-arrhythmic drugs was seen in 85% (95% confidence interval 50-100). Six months after STAR, an 86% reduction (95% confidence interval 80-93) in the number of implantable cardioverter-defibrillator shocks was observed. The rates for improved, unchanged and decreased cardiac ejection fraction were 10%, 84% and 6%, respectively. Overall survival at 6 and 12 months was 89% (95% confidence interval 81-97) and 82% (95% confidence interval 65-98). The cardiac-specific survival at 6 months was 87%. Late grade 3 toxicity occurred in 2% (95% confidence interval 0-5%) with no grade 4-5 toxicity. CONCLUSION: STAR demonstrated both satisfactory efficacy and safety for the management of refractory ventricular tachycardia and was also associated with a significant decline in anti-arrhythmic drugs consumption. These findings support the continued development of STAR as a treatment option.

Final analysis and results of the Phase II SIMPLE dark matter search.

We report the final results of the Phase II SIMPLE measurements, comprising two run stages of 15 superheated droplet detectors each, with the second stage including an improved neutron shielding. The analyses include a refined signal analysis, and revised nucleation efficiency based on a reanalysis of previously reported monochromatic neutron irradiations. The combined results yield a contour minimum of σp=5.7×10(-3) pb at 35 GeV/c2 in the spin-dependent sector of weakly interacting massive particle (WIMP) proton interactions, the most restrictive to date for MW}≤60 GeV/c2 from a direct search experiment and overlapping, for the first time, with results previously obtained only indirectly. In the spin-independent sector, a minimum of 4.7×10(-6) pb at 35 GeV/c2 is achieved, with the exclusion contour challenging a significant part of the light mass WIMP region of current interest.

Molecular characterization of Corynebacterium pseudotuberculosis isolated from goats using ERIC-PCR.

Corynebacterium pseudotuberculosis, the infectious agent of caseous lymphadenitis (CLA), is responsible for substantial economic losses in goat and sheep production. Molecular characterization of C. pseudotuberculosis isolates by enterobacterial repetitive intergenic consensus (ERIC)-PCR has shown promising results in genotyping strains isolated from sheep with CLA. We evaluated the genetic diversity of C. pseudotuberculosis isolates collected from the Sertão region of the Pernambuco (PE) State, Brazil, and investigated the potential of ERIC-PCR as a tool for the molecular typing of strains of C. pseudotuberculosis isolated from goats. Thirty-two C. pseudotuberculosis strains isolated from goats in the municipalities of Floresta and Ibimirim, PE, C. pseudotuberculosis type strain ATCC 19410, the 1002 vaccine strain, and a field isolate of Rhodococcus equi were fingerprinted using the primers ERIC-1R and ERIC-2 and the primer pair ERIC- 1R+ERIC-2. Using 100% similarity as the cutoff, 8, 10, and 7 genotypes were obtained with ERIC-1-PCR, ERIC-2-PCR, and ERIC-1+2-PCR, respectively. The Hunter-Gaston discriminatory index calculated for the ERIC-1-PCR was 0.75. The index for the ERIC-2-PCR was 0.88, and the index for the ERIC-1+2-PCR was 0.79. Among goat isolates of C. pseudotuberculosis, three, two and four genotypes (found by ERIC-1-PCR, ERIC-2-PCR, and ERIC-1+2-PCR, respectively) had been previously described among sheep isolates from Minas Gerais State, Brazil. These results showed that ERIC-PCR has good discriminatory power and typeability, making it a useful tool for discrimination among C. pseudotuberculosis isolates from goats.

Stereotactic radiosurgery for brain metastases from small cell lung cancer without prior whole-brain radiotherapy: A meta-analysis.

OBJECTIVES: Assess upfront Stereotactic radiosurgery (SRS) effectiveness for small cell lung cancer (SCLC) brain metastases (BM). Where possible, a comparison with whole-brain radiotherapy (WBRT) was performed. METHODS: Following PRISMA and MOOSE guidelines, eligible studies were identified on Medline, Embase, Cochrane Library, and proceedings of annual meetings between inception and July 01, 2020. RESULTS: Nine observational studies with 1638 patients were included. The median overall survival (OS) was 8.3 months (95% CI 7.1-9.5 months, I2 = 0%). OS rate at 12 months was 39% (95% CI 31-44%, I2 = 0%). The relative risk between SRS and WBRT for the OS at 12 months was 1.33 (95% CI 1.13-1.51, P = 0.0001). The projected OS for 6, 12, 18- and 24-months comparing SRS with WBRT was 67% vs. 57%, 39% vs. 29%, 22% vs. 15% and 15% vs 9%, favoring SRS (P < 0.001). The LC rate at 12 months was 93% (95% CI 91-94%, I2 = 0%). The distant brain failure rate (DBFR) at 12 months was 41% (95% CI 33-48%, I2 = 52%, P = 0.08). The SRS or WBRT as salvage treatment after upfront SRS was 32% and 19%, respectively. The freedom from neurologic death at 12 months was 87% (95% CI 84-89%). CONCLUSION: Based on the pooling of a large sample of retrospective studies our meta-analysis suggests that for high selected SCLC patients with limited BM upfront SRS produces favorable lesion control and survival outcomes. These findings support the design of randomized clinical trial to confirm the role of SRS in this clinical scenario.

Seroprevalence and risk factors of caprine toxoplasmosis in Minas Gerais, Brazil.

The objective of this work was to carry out a study on caprine toxoplasmosis in the state of Minas Gerais, Brazil. To determine the prevalence of toxoplasmosis in goats in Minas Gerais, 767 sera from goats were tested by ELISA (enzyme-linked immunosorbent assay) and IFAT (indirect fluorescence antibody test). The prevalence of antibodies to Toxoplasma gondii was 43.0% and 46.0% by ELISA and IFAT, respectively. It was observed that 26.8% of the goats show low-avidity IgG to T. gondii. These results suggest the presence of animals in recent phase of toxoplasmosis in Minas Gerais. The risk factors for toxoplasmosis in goats were: age over 36 months (OR=1.21; IC 95% 1.02-1.44), use of pen (OR=1.83; IC 95%1.01-3.31) and pure breed animals (OR=2.49; IC 95% 1.11-5.59).

The evaluation of compliance with iRefer guidelines for abdominal imaging and the impact of the normal abdominal radiograph on the clinical confidence and decision making of emergency clinicians.

INTRODUCTION: Attendance of adult patients to the Emergency Department (ED) with acute abdominal pain is a frequent event. Abdominal X-ray imaging (AXR) is commonly the first line of investigation but previous studies have suggested that the AXR has no place in assessing acute abdominal pain because of its low diagnostic yield and limited contribution to direct clinical decision making. However, no evaluation of the impact of a negative AXR on the clinical confidence and decision making of emergency clinicians has been undertaken. This study aims to fill this gap. METHOD: A self-designed paper questionnaire was distributed to medical clinicians on ED placement at a single NHS trust in the South of England. The survey sought to explore the impact of the negative AXR on clinical confidence and decision making and compliance with iRefer guidelines for referring to alternative imaging modalities (ultrasound and computed tomography) should the option to refer for AXR be restricted. RESULTS: A total of 28 (n = 28/41; 68.3%) completed questionnaires were returned. Most clinicians (n = 18/28; 64.3%) indicated that negative AXR had little impact on their clinical decision making although a small majority (n = 10/18; 55.6%) acknowledged it provided greater clinical confidence in their decision making. Variable compliance with iRefer guidelines for referral to ultrasound and computed tomography was noted. CONCLUSION: Whilst the negative AXR did not impact on the clinical decision making of most ED clinicians, it did increase clinical confidence. Consequently, the AXR should remain a referral option in the workup for adult patients presenting with acute abdominal pain to the emergency department.

Energy restriction, exercise and atorvastatin treatment improve endothelial dysfunction and inhibit miRNA-155 in the erectile tissue of the aged rat.

BACKGROUND: Endothelial dysfunction underlies cardiovascular disease that frequently affects aged individuals. Characterized by local decrease in nitric oxide, it results from down-regulation of endothelial nitric oxide synthase (eNOS) expression/activity. Aiming to elucidate the molecular mechanisms involved in age-related endothelial dysfunction and to unveil potential therapeutic targets, we tested how diet pattern, exercise and atorvastatin modulate the expression of eNOS, inducible NOS (iNOS), endothelin-1, sirtuins (SIRT) and microRNA-155 in the erectile tissue of high-fat fed aged rats. METHODS: Sprague-Dawley male rats fed with high-fat diet until they completed 12 months were grouped and subjected to energy restriction (ER), ER and atorvastatin, or, ER, atorvastatin and physical exercise. Controls were fed with standard rodent chow. The blood pressure was measured using the tail-cuff method before sacrifice at 18 months. Glucose, total cholesterol, HDL, triglyceride and CRP were assessed in blood and eNOS, endothelin-1, iNOS and sirtuins were detected by immunofluorescence in the penis sections; eNOS, endothelin-1, iNOS, SIRT2-4 and SIRT6-7 were semi-quantified by western blotting in tissue homogenates. MicroRNA-155 was quantified using RT-PCR in formalin-fixed paraffin embedded sections. To compare the studied variables, two-tail student t test was used. RESULTS: Atorvastatin promotes eNOS expression and is more efficient than ER or exercise in the control of hyperlipidemia and inflammation. Among the studied sirtuins, detected for the first time in the erectile tissue of the aged rat, SIRT2 aligns with eNOS expression. Both proteins exhibit over-expression in animals with combined exercise, atorvastatin and ER. Analysis of microRNA-155 expression also suggests its intervention in the regulation of eNOS expression. ER, particularly when combined with atorvastatin, was able to reverse the increase of iNOS and endothelin-1 in high-fat fed rats. CONCLUSIONS: The present results indicate that the association of ER, atorvastatin and exercise is more efficient than isolated interventions in the prevention of endothelial dysfunction.

Mediastinal tuberculous lymphadenitis presenting as an esophageal intramural tumor: a very rare but important cause for dysphagia.

Dysphagia associated with esophageal mechanical obstruction is usually related to malignant esophageal diseases. Benign lesions are rarely a cause for this type of dysphagia, and usually occur either as an intramural tumor or as an extrinsic compression. Mediastinal tuberculous lymphadenitis is rare in adults, and even more rarely causes dysphagia. We report two cases of dysphagia in adult patients caused by mediastinal tuberculous lymphadenitis, presenting radiologically and endoscopically as an esophageal submucosal tumor. Based on the clinical and imaging diagnosis, the patients underwent a right thoracotomy, and excision of the mass attached to and compressing the esophagus. Pathological examination of the specimens showed a chronic granulomatous inflammation with caseous necrosis, which was consistent with tuberculous lymphadenitis.

Evaluation of an enhanced service for medication review in Swiss community pharmacies “Médicaments à Jour?”: study protocol

BACKGROUND: In Switzerland, it is estimated that 20,000 people are hospitalized each year as a result of drug related problems (DRP). There are many sources of DRPs, such as incorrect storage or missing dosages from packages. Community pharmacies (CP) are well positioned to identify and manage such DRPs in a timely manner. In Switzerland, no pharmacy service that focus on the management of DRPs is currently recognized and remunerated. A new service, "Médicaments à Jour?" (MaJ?), has been developed. It is focused on DRPs related to self-medication and medication management at home and it includes a systematic review of the patient’s treatment.OBJECTIVE: To evaluate the impact of the MaJ? service for adults with polypharmacy in Swiss CP for the identification and management of DRPs.METHODS: A pre-post intervention study will be carried out in CPs in the canton of Vaud for 15 months. Volunteer pharmacists will include adults with a prescription for at least four chronic and systemic drugs for at least three months. Trained pharmacists will conduct structured consultations with patients at three points (T0, T6, T12) to deliver the service. The primary outcome of the study is the identification and management of DRPs. Secondary outcomes are patients’ knowledge about their treatments, number of expired or untaken medications and description of pharmaceutical interventions.RESULTS: the study has been approved and will be supported by health authorities ("Direction générale de la santé") and local pharmacists association ("Société Vaudoise de Pharmacie"). The Ethics Committee (CER-VD) concluded that the study does not fall under the Human Research Act. It will begin in spring 2022 in 19-35 pharmacies that will recruit at least 162 patients after randomization of eligible patients through a sequence of computer-generated random numbers. (AU)