Acute appendicitis and retroperitoneal abscess: rare complications of sigmoid diverticulitis

Diverticulitis is a common cause of an acute surgical abdomen and computed tomography has become an essential part of work up particularly to identify complications that commonly include intraperitoneal perforation, abscess and fistula formation. We report the case of an 81-year-old male who presented to the emergency department with acute lower abdominal pain and was found to have sigmoid diverticulitis with the rare complications of a diverticular abscess that had formed a sinus tract and perforated into the retroperitoneum and secondary acute appendicitis. Initial management was with intravenous antibiotics, a Hartmann's procedure and appendicectomy. Subsequently the retroperitoneal collection was drained percutaneously. The case was further complicated by the patient's multiple co-morbidities and unfortunately the patient died 6 weeks after admission from sepsis. This case highlights the role of computed tomography in the pre- and post-operative period to identify complications which are often clinically occult and require early surgical and interventional radiology management to optimize outcomes

Dynamic 1^1H Imaging of Hyperpolarized [1-13^{13}C]Lactate In Vivo Using a Reverse INEPT Experiment

$\textbf{Purpose:}$ Dynamic magnetic resonance spectroscopic imaging of hyperpolarized $^{13}$C-labeled cell substrates has enabled the investigation of tissue metabolism in vivo. Currently observation of these hyperpolarized substrates is limited mainly to $^{13}$C detection. We describe here an imaging pulse sequence that enables proton observation by using polarization transfer from the hyperpolarized $^{13}$C nucleus to spin-coupled protons. $\textbf{Methods:}$ The pulse sequence transfers $^{13}$C hyperpolarization to $^1$H using a modified reverse insensitive nuclei enhanced by polarization transfer (INEPT) sequence that acquires a fully refocused echo. The resulting hyperpolarized $^1$H signal is acquired using a 2D echo-planar trajectory. The efficiency of polarization transfer was investigated using simulations with and without T$_1$ and T$_2$ relaxation of both the $^1$H and $^{13}$C nuclei. $\textbf{Results:}$ Simulations showed that $^1$H detection of the hyperpolarized $^{13}$C nucleus in lactate should increase significantly the signal-to-noise ratio when compared with direct $^{13}$C detection at 3T. However the advantage of $^1$H detection is expected to disappear at higher fields. Dynamic $^1$H images of hyperpolarized [1-$^{13}$C]lactate, with a spatial resolution of 1.25 × 1.25 mm$^2$, were acquired from a phantom injected with hyperpolarized [1-$^{13}$C]lactate and from tumors in vivo following injection of hyperpolarized [1-$^{13}$C]pyruvate. $\textbf{Conclusions:}$ The sequence allows $^1$H imaging of hyperpolarized $^{13}$C-labeled substrates in vivo.Grant sponsor: Cancer Research UK Programme; Grant number: 17242; Grant sponsor: CRUK-EPSRC Imaging Centre in Cambridge and Manchester; Grant number: 16465; Grant sponsor: Danish Strategic Research Council (LIFE-DNP: Hyperpolarized magnetic resonance for in vivo quantification of lipid, sugar and amino acid metabolism in lifestyle related diseases); Grant sponsor: Marie Curie ITN studentship (EUROPOL); Grant number: 642773

Cryo-EM Structure and Molecular Dynamics Analysis of the Fluoroquinolone Resistant Mutant of the AcrB Transporter from Salmonella.

Salmonella is an important genus of Gram-negative pathogens, treatment of which has become problematic due to increases in antimicrobial resistance. This is partly attributable to the overexpression of tripartite efflux pumps, particularly the constitutively expressed AcrAB-TolC. Despite its clinical importance, the structure of the Salmonella AcrB transporter remained unknown to-date, with much of our structural understanding coming from the Escherichia coli orthologue. Here, by taking advantage of the styrene maleic acid (SMA) technology to isolate membrane proteins with closely associated lipids, we report the very first experimental structure of Salmonella AcrB transporter. Furthermore, this novel structure provides additional insight into mechanisms of drug efflux as it bears the mutation (G288D), originating from a clinical isolate of Salmonella Typhimurium presenting an increased resistance to fluoroquinolones. Experimental data are complemented by state-of-the-art molecular dynamics (MD) simulations on both the wild type and G288D variant of Salmonella AcrB. Together, these reveal several important differences with respect to the E. coli protein, providing insights into the role of the G288D mutation in increasing drug efflux and extending our understanding of the mechanisms underlying antibiotic resistance

Metabolic control of BRISC–SHMT2 assembly regulates immune signalling

Serine hydroxymethyltransferase 2 (SHMT2) regulates one-carbon transfer reactions that are essential for amino acid and nucleotide metabolism, and uses pyridoxal-5′-phosphate (PLP) as a cofactor. Apo SHMT2 exists as a dimer with unknown functions, whereas PLP binding stabilizes the active tetrameric state. SHMT2 also promotes inflammatory cytokine signalling by interacting with the deubiquitylating BRCC36 isopeptidase complex (BRISC), although it is unclear whether this function relates to metabolism. Here we present the cryo-electron microscopy structure of the human BRISC–SHMT2 complex at a resolution of 3.8 Å. BRISC is a U-shaped dimer of four subunits, and SHMT2 sterically blocks the BRCC36 active site and inhibits deubiquitylase activity. Only the inactive SHMT2 dimer—and not the active PLP-bound tetramer—binds and inhibits BRISC. Mutations in BRISC that disrupt SHMT2 binding impair type I interferon signalling in response to inflammatory stimuli. Intracellular levels of PLP regulate the interaction between BRISC and SHMT2, as well as inflammatory cytokine responses. These data reveal a mechanism in which metabolites regulate deubiquitylase activity and inflammatory signalling

A bi-directional relationship between obesity and health-related quality of life : evidence from the longitudinal AusDiab study

Objective: To assess the prospective relationship between obesity and health-related quality of life, including a novel assessment of the impact of health-related quality of life on weight gain.Design and setting: Longitudinal, national, population-based Australian Diabetes, Obesity and Lifestyle (AusDiab) study, with surveys conducted in 1999/2000 and 2004/2005.Participants: A total of 5985 men and women aged 25 years at study entry.Main outcome measure(s): At both time points, height, weight and waist circumference were measured and self-report data on health-related quality of life from the SF-36 questionnaire were obtained. Cross-sectional and bi-directional, prospective associations between obesity categories and health-related quality of life were assessed.Results: Higher body mass index (BMI) at baseline was associated with deterioration in health-related quality of life over 5 years for seven of the eight health-related quality of life domains in women (all P0.01, with the exception of mental health, P&gt;0.05), and six out of eight in men (all P&lt;0.05, with the exception of role-emotional, P=0.055, and mental health, P&gt;0.05). Each of the quality-of-life domains related to mental health as well as the mental component summary were inversely associated with BMI change (all P&lt;0.0001 for women and P0.01 for men), with the exception of vitality, which was significant in women only (P=0.008). For the physical domains, change in BMI was inversely associated with baseline general health in women only (P=0.023).Conclusions: Obesity was associated with a deterioration in health-related quality of life (including both physical and mental health domains) in this cohort of Australian adults followed over 5 years. Health-related quality of life was also a predictor of weight gain over 5 years, indicating a bi-directional association between obesity and health-related quality of life. The identification of those with poor health-related quality of life may be important in assessing the risk of future weight gain, and a focus on health-related quality of life may be beneficial in weight management strategies.<br /

Distinguishing Asthma Phenotypes Using Machine Learning Approaches.

Asthma is not a single disease, but an umbrella term for a number of distinct diseases, each of which are caused by a distinct underlying pathophysiological mechanism. These discrete disease entities are often labelled as asthma endotypes. The discovery of different asthma subtypes has moved from subjective approaches in which putative phenotypes are assigned by experts to data-driven ones which incorporate machine learning. This review focuses on the methodological developments of one such machine learning technique-latent class analysis-and how it has contributed to distinguishing asthma and wheezing subtypes in childhood. It also gives a clinical perspective, presenting the findings of studies from the past 5 years that used this approach. The identification of true asthma endotypes may be a crucial step towards understanding their distinct pathophysiological mechanisms, which could ultimately lead to more precise prevention strategies, identification of novel therapeutic targets and the development of effective personalized therapies

To determine the level of satisfaction among medical students of a public sector medical university regarding their academic activities

<p>Abstract</p> <p>Background</p> <p>An ongoing evaluation system is essential to determine if the academic system in place has worked to produce a better product, hence the objective of our study was to evaluate the satisfaction level among medical students regarding their academic teaching and assessment method and what measures will they suggest for the future to rectify the current situation.</p> <p>This questionnaire based cross sectional study was conducted in a public sector medical university from February to July 2010. A well structured questionnaire was administered to a random sample of 375 final year medical students. However 292 of the students provided informed consent and filled in the questionnaire which included their demographic profile as well as questions in line with the study objective. Data was entered in a Statistical Package for Social Sciences (SPSS version.16) and analyzed using descriptive statistics.</p> <p>Findings</p> <p>The male to female ratio in our study was 1:2. Most of the students (57.2%) were dissatisfied with the quality of teaching in the university. Fifty-seven percent of the participants believed that the current standard of their institute were not at par with those of international medical universities. BCQ's were the mode of examination questions preferred by the majority of the students. Most of the students (66.1%) wanted the university to conduct career planning seminars to help them plan their career.</p> <p>Conclusions</p> <p>These results suggest that the students of public sector medical universities are unsatisfied from current academic facilities and teaching activities. Students recommend increased emphasis on better lectures and practical training as well as a need to incorporate career planning sessions for the students to help plan them their future career paths.</p

Professional identity formation in the transition from medical school to working life:a qualitative study of group-coaching courses for junior doctors

BACKGROUND: The transition from student to medical doctor is challenging and stressful to many junior doctors. To practice with confidence and professionalism the junior doctors have to develop a strong professional identity. Various suggestions on how to facilitate formation of professional identity have been offered including the possible positive effect of group-coaching courses. The purpose of this study was to explore how group-coaching might facilitate professional identity formation among junior doctors in the transition period. METHODS: Group-coaching courses comprising three whole-day sessions and five 2 h sessions during a period of 4 months were offered to junior doctors in the first years after graduation. The purpose was to support the participants’ professional development, ability to relate to patients, relatives and staff and career development. The coaches in this study had a background as health professionals combined with coaching educations. Data was obtained through observations, open-ended questionnaires and interviews. A generic thematic analysis was applied. RESULTS: Forty-five doctors participated in six coaching groups. The three main themes emerging in the sessions were: Adoption to medical culture, career planning, and work/life-balance. The junior doctors found the coaching intervention highly useful in order to cope with these challenges. Furthermore, the group was a forum where the junior doctors could share thoughts and feelings with colleagues without being afraid that this would endanger their professional career. Many found new ways to respond to everyday challenges mainly through a new awareness of patterns of thinking and feeling. CONCLUSIONS: The participants found that the group-coaching course supported their professional identity formation (thinking, feeling and acting as a doctor), adoption to medical culture, career planning and managing a healthy work/life-balance. Further studies in different contexts are recommended as well as studies using other methods to test the results of this qualitative study. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12909-016-0684-3) contains supplementary material, which is available to authorized users

Interactions Between Laminin Receptor and the Cytoskeleton During Translation and Cell Motility

Human laminin receptor acts as both a component of the 40S ribosomal subunit to mediate cellular translation and as a cell surface receptor that interacts with components of the extracellular matrix. Due to its role as the cell surface receptor for several viruses and its overexpression in several types of cancer, laminin receptor is a pathologically significant protein. Previous studies have determined that ribosomes are associated with components of the cytoskeleton, however the specific ribosomal component(s) responsible has not been determined. Our studies show that laminin receptor binds directly to tubulin. Through the use of siRNA and cytoskeletal inhibitors we demonstrate that laminin receptor acts as a tethering protein, holding the ribosome to tubulin, which is integral to cellular translation. Our studies also show that laminin receptor is capable of binding directly to actin. Through the use of siRNA and cytoskeletal inhibitors we have shown that this laminin receptor-actin interaction is critical for cell migration. These data indicate that interactions between laminin receptor and the cytoskeleton are vital in mediating two processes that are intimately linked to cancer, cellular translation and migration

Unemployment and disability pension-an 18-year follow-up study of a 40-year-old population in a Norwegian county

<p>© 2012 Støver et al; licensee BioMed Central Ltd.</p><p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.</p