Preoperative 99mTc-sestamibi scintigraphy in patients with primary hyperparathyroidism and concomitant nodular goiter: Comparison of SPECT-CT, SPECT, and planar imaging

Background: Investigations using a hybrid single photon emission computed tomography/computed tomography (SPECT-CT) scanning technique have been carried out in limited studies and have shown mixed results. However, the assessment of this technique for the detection of parathyroid adenoma in patients with a nodular goiter was performed in only one study with a small sample size. The aim of this prospective study was to assess the role of Tc-sestamibi parathyroid SPECT-CT scans for localization of parathyroid adenomas with a concomitant nodular goiter using Tc-methoxyisobutyl isonitrile (MIBI) scintigraphy and to compare it with SPECT and planar imaging. Methods: This study was conducted on 48 patients with primary hyperparathyroidism and nodular goiter, who were candidates for parathyroid surgery and had been referred for parathyroid scintigraphy. The patients underwent an early set of planar Tc-MIBI scanning procedures first, followed by SPECT and CT scannings, and finally a delayed set of planar Tc-MIBI scannings. Sensitivity, specificity, negative and positive predictive values, and accuracy were determined on a per-parathyroid-gland basis for each scanning method, as defined by histology and follow-up. Results: The surgery was successful in 48 out of 50 patients with primary hyperparathyroidism concomitant with thyroid nodularity, and data were completed for 80 sites in 48 patients. The accuracy of SPECT-CT in correctly identifying a parathyroid adenoma was 85.00, versus 75.00% for SPECT (P=0.01, significant). The sensitivity and specificity for SPECT-CT were 77.55 and 96.77%, respectively, versus 67.34 and 87.09%, respectively, for SPECT (P=0.12 and 0.12, not significant). There were nine sites that showed better localization on SPECT-CT scans relative to SPECT images, of which five sites were located in the ectopic regions. Conclusion: The results of our study indicate that SPECT-CT is more accurate than sestamibi planar imaging and SPECT for the preoperative identification of parathyroid lesions in patients with primary hyperparathyroidism concomitant with thyroid nodularity. Also, we would recommend the use of SPECT-CT for a workup of all patients with ectopic glands who are scheduled for minimally invasive parathyroid surgery. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

DM2 platform II : AI-assisted optimization of oral solid dosage form development

Digital Medicines Manufacturing (DM2) platform II aims to leverage AI to develop an autonomous workflow for drug product manufacturing and testing system by identifying optimal formulation and process parameters that deliver desired critical quality attributes (CQAs). This approach aims to de-risk and accelerate drug product development by reducing experiments, development time, and materials use by 60%. The initial objective is to develop a database of hundreds of historical data and new experiments. This database is then used to develop a hybrid machine for predicting product (tablets and capsules) attributes by utilizing domain knowledge (empirical/mechanistic models) and AI-powered models (where domain knowledge is not available/reliable). The hybrid machine is then integrated into an iterative, model-informed optimization framework, to smartly plan experiments that drive the automated manufacturing and testing system, which will be used to collect multi-scale and –point data and update the model(s) to learn from the experiments. Fit-for-purpose optimization algorithms will be employed to execute this loop based on the objective of experiments (i.e. exploration of the knowledge space or exploitation of the model-based optimization) and it continues until the targets are achieved. The proposed smart experimental planning method has been tested using the Gurnham (empirical) model as a predictor of porosity based on peak compression pressure. The initial analysis of the uncertainty of fit demonstrates that adding only 1 data point results in a 20-fold improvement in the accuracy of prediction while adding 8 more data points leads to a minimal improvement, highlighting the significance of the here-developed smart experimental planning procedure in achieving acceptable prediction accuracy at a minimal experimentation cost

DM2 platform II : development of an automated microscale manufacturing system for oral solid dosage forms

This platform aims to create a unique autonomous microscale drug product manufacturing and testing system to select formulation and process parameters that result in a stable product with desired critical quality attributes. The number of experiments increases drastically with the number of excipients, drug loadings and process conditions that need to be explored to find the optimal formulation and process settings. Integrating industrial digital technologies (IDTs) with innovative pharmaceutical process technologies will de-risk and accelerate drug product manufacture, reducing experiments and dramatically reducing development time and raw material/solvents use by 60%, whilst achieving CQA objectives by self-optimized formulation and process conditions. The platform is codeveloped and co-delivered with industry partners focusing on 1) tablets (via direct compression) and 2) capsules (via powder fill) . The initial aim of this platform is to deliver an automated microscale batch manufacturing system that ca n eliminate waste while preparing tablet batches of < 10 g per batch and < 50 tablets per batch

Oesophageal cancer among the Turkomans of northeast Iran

A Caspian Littoral Cancer Registry survey in the early 1970s established northern Iran as one of the highest oesophageal cancer incidence regions of the world. To verify this, an oesophageal cancer survey was carried out between 1995 and 1997 in the Turkoman Plain at the southeastern corner of the Caspian Sea. Oesophageal balloon cytology screening was carried out on 4192 asymptomatic adults above age 30 years in one town and three adjoining villages with a total population of 20 392 people at risk. Oesophagoscopy was performed on 183 patients with abnormal cytological findings. The discovery of two asymptomatic small squamous cell cancers and one ‘carcinoma- suspect’ implied a prevalence ranging from 47.7 per 100 000 to 71.5 per 100 000. During a 1-year active surveillance, 14 patients were found with clinically advanced oesophageal squamous cell cancer, yielding age-standardized incidence rates of 144.09 per 100 000 for men and 48.82 per 100 000 for women. The very high frequency of oesophageal cancer reported for northern Iran 25 years ago stands confirmed. Differences in incidence rates, then and now, can be attributed to survey methods used and diagnostic criteria applied, but not to socioeconomic factors, which have remained relatively stable. Oesophageal balloon cytology is a practical method of mass screening for oesophageal cancer in Iran. © 2000 Cancer Research Campaig

Allelic variants of the NLR protein Rpi-chc1 differentially recognize members of the Phytophthora infestans PexRD12/31 effector superfamily through the leucine-rich repeat domain

Phytophthora infestans is a pathogenic oomycete that causes the infamous potato late blight disease. Resistance (R) genes from diverse Solanum species encode intracellular receptors that trigger effective defense responses upon the recognition of cognate RXLR avirulence (Avr) effector proteins. To deploy these R genes in a durable fashion in agriculture, we need to understand the mechanism of effector recognition and the way the pathogen evades recognition. In this study, we cloned 16 allelic variants of the Rpi-chc1 gene from Solanum chacoense and other Solanum species, and identified the cognate P. infestans RXLR effectors. These tools were used to study effector recognition and co-evolution. Functional and non-functional alleles of Rpi-chc1 encode coiled-coil nucleotide-binding leucine-rich repeat (CNL) proteins, being the first described representatives of the CNL16 family. These alleles have distinct patterns of RXLR effector recognition. While Rpi-chc1.1 recognized multiple PexRD12 (Avrchc1.1) proteins, Rpi-chc1.2 recognized multiple PexRD31 (Avrchc1.2) proteins, both belonging to the PexRD12/31 effector superfamily. Domain swaps between Rpi-chc1.1 and Rpi-chc1.2 revealed that overlapping subdomains in the leucine-rich repeat (LRR) domain are responsible for the difference in effector recognition. This study showed that Rpi-chc1.1 and Rpi-chc1.2 evolved to recognize distinct members of the same PexRD12/31 effector family via the LRR domain. The biased distribution of polymorphisms suggests that exchange of LRRs during host–pathogen co-evolution can lead to novel recognition specificities. These insights will guide future strategies to breed durable resistant varieties

Percutaneous closure of atrial septal defects leads to normalisation of atrial and ventricular volumes

Background: Percutaneous closure of atrial septal defects (ASDs) should potentially reduce right heart volumes by removing left-to-right shunting. Due to ventricular interdependence, this may be associated with impaired left ventricular filling and potentially function. Furthermore, atrial changes post-ASD closure have been poorly understood and may be important for understanding risk of atrial arrhythmia post-ASD closure. Cardiovascular magnetic resonance (CMR) is an accurate and reproducible imaging modality for the assessment of cardiac function and volumes. We assessed cardiac volumes pre- and post-percutaneous ASD closure using CMR. Methods: Consecutive patients (n = 23) underwent CMR pre- and 6 months post-ASD closure. Steady state free precession cine CMR was performed using contiguous slices in both short and long axis views through the ASD. Data was collected for assessment of left and right atrial, ventricular end diastolic volumes (EDV) and end systolic volumes (ESV). Data is presented as mean ± SD, volumes as mL, and paired t-testing performed between groups. Statistical significance was taken as p &lt; 0.05. Results: There was a significant reduction in right ventricular volumes at 6 months post-ASD closure (RVEDV: 208.7 ± 76.7 vs. 140.6 ± 60.4 mL, p &lt; 0.0001) and RVEF was significantly increased (RVEF 35.5 ± 15.5 vs. 42.0 ± 15.2%, p = 0.025). There was a significant increase in the left ventricular volumes (LVEDV 84.8 ± 32.3 vs. 106.3 ± 38.1 mL, p = 0.003 and LVESV 37.4 ± 20.9 vs. 46.8 ± 18.5 mL, p = 0.016). However, there was no significant difference in LVEF and LV mass post-ASD closure. There was a significant reduction in right atrial volumes at 6 months post-ASD closure (pre-closure 110.5 ± 55.7 vs. post-closure 90.7 ± 69.3 mL, p = 0.019). Although there was a trend to a decrease in left atrial volumes post-ASD closure, this was not statistically significant (84.5 ± 34.8 mL to 81.8 ± 44.2 mL, p = NS). Conclusion: ASD closure leads to normalisation of ventricular volumes and also a reduction in right atrial volume. Further follow-up is required to assess how this predicts outcomes such as risk of atrial arrhythmias after such procedures.Karen SL Teo, Benjamin K Dundon, Payman Molaee, Kerry F Williams, Angelo Carbone, Michael A Brown, Matthew I Worthley, Patrick J Disney, Prashanthan Sanders and Stephen G Worthle

Paternal Origins and Migratory Episodes of Domestic Sheep

Deng et al. show that domestic sheep harbor four Y chromosome lineages and early expansions of sheep were associated with the segregation of primitive and fat-tailed phenotypes as well as traits selected for different purposes

Repaired tetralogy of Fallot: the roles of cardiovascular magnetic resonance in evaluating pathophysiology and for pulmonary valve replacement decision support

Surgical management of tetralogy of Fallot (TOF) results in anatomic and functional abnormalities in the majority of patients. Although right ventricular volume load due to severe pulmonary regurgitation can be tolerated for many years, there is now evidence that the compensatory mechanisms of the right ventricular myocardium ultimately fail and that if the volume load is not eliminated or reduced by pulmonary valve replacement the dysfunction might be irreversible. Cardiovascular magnetic resonance (CMR) has evolved during the last 2 decades as the reference standard imaging modality to assess the anatomic and functional sequelae in patients with repaired TOF. This article reviews the pathophysiology of chronic right ventricular volume load after TOF repair and the risks and benefits of pulmonary valve replacement. The CMR techniques used to comprehensively evaluate the patient with repaired TOF are reviewed and the role of CMR in supporting clinical decisions regarding pulmonary valve replacement is discussed

Molecular detection of Chlamydia Trachomatis and Mycoplasma Hominis in endometriosis lesions

Background: Retrograde of menstrual blood into the peritoneal cavity is one of the accepted theories for initiation of endometriosis although indicated that other factors are involved in pathogenesis. Investigation of infectious agents is important in this regard. Objective: To investigate the presence of bacterial infections; Chlamydia trachomatis and Mycoplasma Hominis as risk factors in endometriosis lesions. Methods: This case-control study was conducted in Sarem Hospital in 2014. DNA was extracted from 90 paraffin-embedded blocks included 40 endometriosis tissue samples, 23 samples of endometrial tissue from the same patients and 27 samples of endometrial tissue of the patients without endometriosis, and molecular analysis were performed using polymerase chain reaction. Results were analyzed by Fisher Exact Test and McNemar Test. Findings: Chlamydia trachomatis infection was seen in 11 (27.5%) endometriosis tissue, 3 (13%) normal tissue from patients and 10 (37%) in patient without endometriosis. Mycoplasma hominis was diagnosed in 11 (27.5%) endometriosis tissue, 7 (30.4%) of normal tissue from patients and one patient without endometriosis (3.7%). These differences show significant relations between infection with Mycoplasma hominis and endometriosis. Conclusion: The findings of this study did not show significant association between Chlamydia trachomatis infections and endometriosis. However; it seems Mycoplasma hominis infection can increase the risk of endometriosis incidence. Keywords: Endometriosis, Molecular Diagnostic, Chlamydia trachomatis, Mycoplasma homini

Inventaire de quelques espèces de la flore de l'Iran utilisées en thérapeutique

Salehian A., Ghodsi M. B., Mahdyon F. Inventaire de quelques espèces de la flore de l'Iran utilisées en thérapeutique. In: Bulletin mensuel de la Société linnéenne de Lyon, 42ᵉ année, n°8, octobre 1973. pp. 212-216