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The inducible degrader of LDL receptor (IDOL) acts as a post-transcriptional degrader of the LDL receptor (LDLR). IDOL is functionally active in the liver and in peripheral tissues. We have evaluated IDOL expression in circulating monocytes in subjects with and without type 2 diabetes and determined whether changes in IDOL expression could affect macrophage function like cytokine production in vitro. One hundred forty individuals with type 2 diabetes and 110 healthy control subjects were recruited. Cellular expression of IDOL and LDLR in peripheral blood CD14+ monocytes was measured by flow cytometry. The expression of intracellular IDOL was lower in individuals with diabetes than control (21.3 ± 4.6 mean fluorescence intensity × 1,000 vs. 23.8 ± 6.2, P < 0.01), and this was accompanied by an increase in cell surface LDLR (5.2 ± 3.0 mean fluorescence intensity × 1,000 vs. 4.3 ± 1.5, P < 0.01), LDL binding, and intracellular lipid (P < 0.01). IDOL expression correlated with HbA1c (r = -0.38, P < 0.01) and serum fibroblast growth factor-21 (FGF21) (r = -0.34, P < 0.01). Multivariable regression analysis, including age, sex, BMI, smoking, HbA1c, and log(FGF21), showed that HbA1c and FGF21 were significant independent determinants of IDOL expression. IDOL knockdown human monocyte-derived macrophages produced higher concentrations of interleukin 1 beta, interleukin 6, and TNFα than control macrophages upon stimulation with lipopolysaccharide (all P < 0.01). In conclusion, the expression of IDOL in CD14+ monocytes was decreased in type 2 diabetes and was associated with glycemia and serum FGF21 concentration., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Previous studies have analyzed the efficacy of near-infrared spectroscopy-derived lipid core burden index (LCBI) in quantifying and identifying high-risk plaques and patients at increased risk of future major adverse cardiac outcomes/major adverse cardiovascular and cerebrovascular events. A maxLCBI 4mm of 400 or greater seems to be an effective threshold for classifying at-risk plaques. This meta-analysis provides a more precise odds ratio with a narrow standard deviation that can be used to guide future studies., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Magseed is an alternative method of localising non-palpable breast lesions that has addressed many of the limitations of wire guided localisation (WGL). It consists of a paramagnetic seed that can be visualised on mammography and ultrasound. Intraoperative localisation of the seed is achieved with the use of the Sentimag probe. The aim of this study was to prospectively compare localisation in patients undergoing wide local excision (WLE) for non-palpable lesions between Magseed and WGL., Methods: We prospectively collected data on all patients undergoing image-guided WLE between October 2017 and September 2018 in two academic breast units with a planned accrual of 100 consecutive patients undergoing Magseed localisation. Data was also collected on a cohort of 100 consecutive patients undergoing WGL in the same time period., Results: Demographic and disease characteristics were well balanced between the two groups. 4/104 patients were converted preoperatively from Magseed to WGL (2 misplaced Magseeds; 2 undetected Magseeds). Intraoperative identification and excision of the localised lesion was successful in all patients as confirmed with specimen radiography. Overall no significant differences were observed in the proportion of patients requiring re-excision between the two groups (Magseed 16% vs. WGL 14% p = 0.692). Specimens size by weight and volume was similar for both groups (Magseed 39.6 g vs. WGL 44.5 g p = 0.206 and 90.1 cm 3 for Magseed vs. 95.6 cm 3 for WGL p = 0.579)., Conclusions: In our series Magseed localisation proved to be as reliable and effective as WGL in terms of lesion identification, excision with tumour free margins and specimen weight., (Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Type VII secretion systems (ESX) are responsible for transport of multiple proteins in mycobacteria. How different ESX systems achieve specific secretion of cognate substrates remains elusive. In the ESX systems, the cytoplasmic chaperone EspG forms complexes with heterodimeric PE-PPE substrates that are secreted from the cells or remain associated with the cell surface. Here we report the crystal structure of the EspG 1 chaperone from the ESX-1 system determined using a fusion strategy with T4 lysozyme. EspG 1 adopts a quasi 2-fold symmetric structure that consists of a central β-sheet and two α-helical bundles. In addition, we describe the structures of EspG 3 chaperones from four different crystal forms. Alternate conformations of the putative PE-PPE binding site are revealed by comparison of the available EspG 3 structures. Analysis of EspG 1 , EspG 3 , and EspG 5 chaperones using small-angle X-ray scattering reveals that EspG 1 and EspG 3 chaperones form dimers in solution, which we observed in several of our crystal forms. Finally, we propose a model of the ESX-3 specific EspG 3 -PE5-PPE4 complex based on the small-angle X-ray scattering analysis., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: Falls are a major source of injury in the elderly and their incomplete management is a cause for concern by health systems. The present study looks at the current state of managing fall victims in Iran and offers suggestions for improvement., Methods: This was a clinical care audit comparing the state of current care with an institutionally approved optimum. Patients aged 60 years and over presenting with a fall were evaluated and deficiencies in their care were recorded and categorized. These were presented to an expert panel, where the Delphi method was used to come up with a list of actions to address the deficiencies. Furthermore an educational program was implemented based on these suggestions. Chi-squared and t-test were used to evaluate the efficacy of this program in improving treatment. Linear regression analysis was used to find factors affecting care., Results: Overall 431 cases were reviewed. The most common errors during clinical examination were: not performing Romberg test (92.75%) and lack of physiotherapy consultation (82.75%). The educational program had a modest effect on improving the clinical audit processes (β = 3.79; P < 0.001) and medical interventions (β = 2.004; P = 0.002); however, performing the correct diagnostic tests was worse after the program (β = -1.21; P = 0.008)., Conclusion: There is a wide gap between the care services delivered in the management of falls and international standards. Therefore, measures should be adopted to close this gap. Education may have a modest positive effect in this regard., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Purpose: Integrating radiation protection (RP) education in the undergraduate medical curriculum is gaining importance and is mandatory in certain jurisdictions. An e-learning module for RP was developed at the authors' medical school and was integrated into year 4 of the 5-year undergraduate medical program. The aim of this study was to investigate its impact on RP knowledge, student preferences for various teaching methods, self-assessment of RP knowledge, and perceptions of career prospects in radiology. Likert-type 5-point scale evaluations and general comments about the RP module and various methods of teaching were also obtained., Methods: An e-learning module in RP was designed and presented to year 4 medical undergraduates. All students were required to complete premodule and postmodule questionnaires., Results: Eighty-nine percent (n = 113) and 99% (n = 126) of the 127 medical students successfully completed and returned the premodule and postmodule questionnaires, respectively. After the e-learning module, students' postmodule RP knowledge had improved significantly. Analysis of postmodule RP knowledge suggested that a favorable self-assessment of knowledge of RP, perception of career prospects in radiology, and completion of the e-learning module with an increased number of sessions were factors predictive of improved RP knowledge. Students expressed a preference for didactic lectures and clinical attachment for instruction in RP over e-learning., Conclusions: The development of an e-learning module in RP is feasible and results in improved knowledge of RP among medical undergraduates. Combining e-learning and more traditional educational programs such as a clinical radiology rotation is likely to improve student experience., (Copyright © 2012 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Basal cell carcinomas are the most prevalent of all skin cancers worldwide and form the majority of the surgical workload for most modern cutaneous malignancy centres. Primary surgical removal of basal cell carcinomas remains the gold standard of treatment but, despite almost two centuries of surgical experience, rates of incomplete surgical excision of up to 50% are still reported. The aim of this study was to assess, quantify and perform comparative analysis of the outcomes and predictive factors of consecutive primarily-excised basal cell carcinomas in a tertiary centre over a six-year period., Methods: Retrospective audit was conducted on all patients who underwent surgical excision of basal cell carcinomas from January 2000 to December 2005. Assessment parameters included patient biographics, tumour management differences and detailed histopathological analysis of tumour margins and subtypes., Results: One thousand eight hundred and thirty two basal cell carcinomas were excised from 1329 patients over the designated time period. Two hundred and fifty one (14%) lesions were incompletely excised with 135 (7.4%) involving the peripheral margin only, 48 (2.6%) the deep margin only and 41 (2.2%) involving both. Nasal location was the most common predictor of incomplete excision., Conclusions: Overall basal cell carcinomas excision rates compared favourably with international reported standards but attention to a variety of surgical and histological risk factors may improve this further., (Copyright © 2010 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Retroperitoneal fibrosis is characterized by the presence of a retroperitoneal tissue, consisting of chronic inflammation and marked fibrosis, which entraps the retroperitoneal organs. In two-thirds of cases, the retroperitoneal fibrosis is idiopathic. The pathogenic mechanism is not clearly identified. We report a case of idiopathic retroperitoneal fibrosis associated with type 1 diabetes mellitus. A 61-year-old woman with C peptide negative insulindependent diabetes developed retroperitoneal fibrosis revealed by bilateral hydronephrosis. Anti-GAD 65 antibodies were positive. There were no signs of autoimmune pancreatitis: no steatorrhea, normal IgG4 isotype levels, and absence of pancreas morphological abnormalities.

The structure of Mycobacterium tuberculosis dUTP nucleotidohydrolase (dUTPase) has been determined at 1.3 Angstrom resolution in complex with magnesium ion and the non-hydrolyzable substrate analog, alpha,beta-imido dUTP. dUTPase is an enzyme essential for depleting potentially toxic concentrations of dUTP in the cell. Given the importance of its biological role, it has been proposed that inhibiting M.tuberculosis dUTPase might be an effective means to treat tuberculosis infection in humans. The crystal structure presented here offers some insight into the potential for designing a specific inhibitor of the M.tuberculosis dUTPase enzyme. The structure also offers new insights into the mechanism of dUTP hydrolysis by providing an accurate representation of the enzyme-substrate complex in which both the metal ion and dUTP analog are included. The structure suggests that inclusion of a magnesium ion is important for stabilizing the position of the alpha-phosphorus for an in-line nucleophilic attack. In the absence of magnesium, the alpha-phosphate of dUTP can have either of the two positions which differ by 4.5 Angstrom. A transiently ordered C-terminal loop further assists catalysis by shielding the general base, Asp83, from solvent thus elevating its pK(a) so that it might in turn activate a tightly bound water molecule for nucleophilic attack. The metal ion coordinates alpha, beta, and gamma phosphate groups with tridentate geometry identical with that observed in the crystal structure of DNA polymerase beta complexed with magnesium and dNTP analog, revealing some common features in catalytic mechanism.