Quantification of dopamine transporter binding using [18F]FP-beta-CIT and positron emission tomography.

The purpose of this study was to compare different kinetic and semi-quantitative methods for analysing human [18F]FP-beta-CIT studies: plasma input models, simplified (SRTM) and full (FRTM) reference tissue models, standard uptake values (SUV) and SUV ratios (SUVr). Both simulations and clinical evaluations were performed to determine the effects of noise, scan duration and blood volume on Akaike model selection, and on precision and accuracy of estimated parameters. For typical noise levels (COV approximately 2.5%) and scan durations (<90 mins), simulations provided poor fits (Akaike criterion) in case of reversible plasma input models showing a relatively high number of outliers compared with the two-tissue irreversible model. Reference tissue models provided more reliable fits, which were nearly independent of noise and scan duration. For clinical data, two tissue irreversible and reversible plasma input models fitted striatum curves equally well (Akaike criterion). BP with plasma input models were less precise and contained more outliers than BP obtained with SRTM or FRTM. Among all methods tested, SRTM showed the highest contrast between patients and controls. When differentiating between patients and controls, SUVr performed almost equally well as SRTM, although contrast between striatum and background was lower. In conclusion, SRTM provided BP estimates with the highest precision and accuracy. Moreover, SRTM provided good contrast between patients and controls, and between striatum and background. SRTM is therefore the method of choice for quantitative [18F]FP-beta-CIT studies. SUVr might be an alternative for larger clinical trials.     

Causes of late onset epilepsy in Saudi Arabia: the role of cerebral granuloma.

Cerebral granulomas, due to infections, have been rarely reported as a cause of late onset epilepsy. The incidence of cerebral granulomas was 7% in this prospective study of 56 consecutive patients with onset of seizures after the age of 20 years. Other main causes included cerebral tumours (20%), arteriovenous malformations (5%) and cerebrovascular disease (15% amongst patients with onset of seizures above the age of 40 years). The incidence of structural abnormalities was higher with increasing age at the onset of seizures and declined with long duration of history of epilepsy. Simple partial seizures were strongly associated with structural abnormalities (86%) as opposed to complex partial (33%) and generalised tonic-clonic seizures (33%).     

Biomaterial microarrays: rapid, microscale screening of polymer-cell interaction

The identification of biomaterials that induce optimal gene expression patterns and allow for appropriate levels of cellular attachment is of central importance in tissue engineering and cell therapy. Herein, we describe the creation of cell-compatible, biomaterial microarrays, that allow rapid, microscale testing of biomaterial interactions with cells. As proof of principle, we simultaneously characterized over 3456 human mesenchymal stem cell (hMSC)-biomaterial composite interactions, and describe preliminary studies on the utility of these arrays with a neural stem cell line (NSC), and primary articular chondrocytes.     

Pathophysiology of mild endometriosis: review of literature

Endometriosis is a puzzling condition and the literature ischaracterized by a large number of uncontrolled reports on itsaetiology and pathophysiology. In particular the relationshipbetween mild endometriosis and subfecundity is uncertain. Thispaper critically reviews the published literature on the pathogenesis,prevalence, menstrual symptomatology and natural history ofendometriosis. Furthermore, factors implicated in causing subfecundityin relation to endometriosis and the impact of various treatmentsin enhancing fertility among women with mild endometriosis havebeen assessed.     

Regulation of T-cell receptor signalling by membrane microdomains

There is now considerable evidence suggesting that the plasma membrane of mammalian cells is compartmentalized by functional lipid raft microdomains. These structures are assemblies of specialized lipids and proteins and have been implicated in diverse biological functions. Analysis of their protein content using proteomics and other methods revealed enrichment of signalling proteins, suggesting a role for these domains in intracellular signalling. In T lymphocytes, structure/function experiments and complementary pharmacological studies have shown that raft microdomains control the localization and function of proteins which are components of signalling pathways regulated by the T-cell antigen receptor (TCR). Based on these studies, a model for TCR phosphorylation in lipid rafts is presented. However, despite substantial progress in the field, critical questions remain. For example, it is unclear if membrane rafts represent a homogeneous population and if their structure is modified upon TCR stimulation. In the future, proteomics and the parallel development of complementary analytical methods will undoubtedly contribute in further delineating the role of lipid rafts in signal transduction mechanisms.     

The Safety and Efficacy of Using Drainage in Arthroscopic Rotator Cuff Repair

PurposeThis study aimed to evaluate the effects of not using a drain or placing a drain in the glenohumeral (GH) or subacromial (SA) joint spaces on fluid retention and pain in the early postoperative period and late clinical outcomes.MethodsPatients who underwent arthroscopic rotator cuff repair between 2018 and 2020 were included in the study. Before the operation, demographic data, range of motion (ROM), visual analog scale (VAS) scores, Constant–Murley scores has documented. Deltoid muscle diameter (DMD) were measured. The total amount of irrigation used during the surgery and the operation duration were recorded, and the active amount of fluid coming from the drain in patients with a drain was recorded. The first postoperative DMD measure was made in the operating room and accepted as day 0. DMD measurements repeated postoperative first and second day. VAS assessments were performed on the postoperative first and second days. At the outpatient clinic, these measurements were repeated on the first and second weeks after discharge. Functional evaluations were made with ROM and Constant–Murley scores at the final follow-up examination.ResultsThere was no difference in the amount of drainage between the two groups in which a drain was used. When the three groups were compared among themselves regarding preoperative and postoperative VAS scores, Constant–Murley scores, and DMD, no significant difference was found.ConclusionsWe do not recommend the routine use of drains after arthroscopic rotator cuff surgery in terms of cost-effectiveness.Level of evidenceLevel II: Prospective Cohort Study.     

Second-generation peptidomimetic inhibitors of protein farnesyltransferase demonstrating improved cellular potency and significant in vivo efficacy.

The synthesis and evaluation of analogues of previously reported farnesyltransferase inhibitors, pyridyl benzyl ether 3 and pyridylbenzylamine 4, are described. Substitution of 3 at the 5-position of the core aryl ring resulted in inhibitors of equal or less potency against the enzyme and decreased efficacy in a cellular assay against Ras processing by the enzyme. Substitution of 4 at the benzyl nitrogen yielded 26, which showed improved efficacy and potency and yet presented a poor pharmacokinetic profile. Further modification afforded 30, which demonstrated a dramatically improved pharmacokinetic profile. Compounds 26 and 29 demonstrated significant in vivo efficacy in nude mice inoculated with MiaPaCa-2, a human pancreatic tumor-derived cell line.