Clarifying Dopaminergic Projections of the Ventral Tegmental Area and Substantia Nigra in Humans using Structural Magnetic Resonance Imaging

Background Dopaminergic (DA) pathways from the human midbrain to the striatum mediate movement, decision making, learning, and reward processing. Classically, the scientific consensus has been that there are two main DA pathways: the nigrostriatal and the mesolimbic pathways. In the nigrostriatal pathway, the substantia nigra par compacta (SNc) sends DA to the dorsal striatum (DS), and in the mesolimbic pathway, the ventral tegmental area (VTA) sends DA to the ventral striatum (VS) as well as prefrontal and limbic cortices. Recent findings, however, cast doubt on the accuracy of this model. It seems likely these DA projections are more overlapping and dispersed. This study aims to re-evaluate this model using ultra-high field magnetic resonance imaging (MRI). Methods By scanning twenty-six healthy participants using 7T MRI, we aim to a) outline and distinguish the SNc and VTA and b) methodically track the projections from SNc and VTA to the striatum and cortex, and their secondary projections. The utilization of 7T over 3T will aid in distinguishing these small brain regions. Results We expect to discover patterns at odds with the current view that SNc versus VTA are entirely distinct DA pathways mediating movement and cognition respectively. Discussion and Conclusion This research will yield a greater understanding of the DA pathways of the human brain, which has applications for research uncovering the complex human functions that implicate and depend upon DA pathways. Interdisciplinary Reflection Exploring the midbrain DA pathways will help elucidate the role of DA pathways in movement and important cognitive functions

Idiopathic benign retroperitoneal cyst: a case report

<p>Abstract</p> <p>Introduction</p> <p>Retroperitoneal cysts are uncommon, with an estimated incidence of 1/5750 to 1/250,000.</p> <p>Case presentation</p> <p>A male patient was admitted with an abdominal pain, jaundice and fever. Clinical examination and investigations confirmed an idiopathic benign retroperitoneal cyst. He underwent surgery and was discharged after making good recovery.</p> <p>Conclusion</p> <p>Retroperitoneal cysts are very rare, and most of the time they are discovered incidentally. Patients may be asymptomatic or present with abdominal pain, referred pain to the legs or weight loss. Imaging may help diagnose these lesions, but surgery is the keystone in confirming the diagnosis. This case is very rare and very educational as it highlights an unusual presentation of a benign retroperitoneal cyst. In our patient, the course of the disease was unique as the patient presented with jaundice.</p

The academic backbone: longitudinal continuities in educational achievement from secondary school and medical school to MRCP(UK) and the specialist register in UK medical students and doctors

Background: Selection of medical students in the UK is still largely based on prior academic achievement, although doubts have been expressed as to whether performance in earlier life is predictive of outcomes later in medical school or post-graduate education. This study analyses data from five longitudinal studies of UK medical students and doctors from the early 1970s until the early 2000s. Two of the studies used the AH5, a group test of general intelligence (that is, intellectual aptitude). Sex and ethnic differences were also analyzed in light of the changing demographics of medical students over the past decades. Methods: Data from five cohort studies were available: the Westminster Study (began clinical studies from 1975 to 1982), the 1980, 1985, and 1990 cohort studies (entered medical school in 1981, 1986, and 1991), and the University College London Medical School (UCLMS) Cohort Study (entered clinical studies in 2005 and 2006). Different studies had different outcome measures, but most had performance on basic medical sciences and clinical examinations at medical school, performance in Membership of the Royal Colleges of Physicians (MRCP(UK)) examinations, and being on the General Medical Council Specialist Register. Results: Correlation matrices and path analyses are presented. There were robust correlations across different years at medical school, and medical school performance also predicted MRCP(UK) performance and being on the GMC Specialist Register. A-levels correlated somewhat less with undergraduate and post-graduate performance, but there was restriction of range in entrants. General Certificate of Secondary Education (GCSE)/O-level results also predicted undergraduate and post-graduate outcomes, but less so than did A-level results, but there may be incremental validity for clinical and post-graduate performance. The AH5 had some significant correlations with outcome, but they were inconsistent. Sex and ethnicity also had predictive effects on measures of educational attainment, undergraduate, and post-graduate performance. Women performed better in assessments but were less likely to be on the Specialist Register. Non-white participants generally underperformed in undergraduate and post-graduate assessments, but were equally likely to be on the Specialist Register. There was a suggestion of smaller ethnicity effects in earlier studies. Conclusions: The existence of the Academic Backbone concept is strongly supported, with attainment at secondary school predicting performance in undergraduate and post-graduate medical assessments, and the effects spanning many years. The Academic Backbone is conceptualized in terms of the development of more sophisticated underlying structures of knowledge ('cognitive capital’ and 'medical capital’). The Academic Backbone provides strong support for using measures of educational attainment, particularly A-levels, in student selection

General practitioners and tutors' experiences with peer group academic detailing: a qualitative study

<p>Abstract</p> <p>Background</p> <p>The Prescription Peer Academic Detailing (Rx-PAD) project is an educational intervention study aiming at improving GPs' competence in pharmacotherapy. GPs in CME peer groups were randomised to receive a tailored intervention, either to support a safer prescription practice for elderly patients or to improve prescribing of antibiotics to patients with respiratory tract infections. The project was based on the principles of peer group academic detailing, incorporating individual feedback on GPs' prescription patterns. We did a study to explore GPs and tutors' experiences with peer group academic detailing, and to explore GPs' reasons for deviating from recommended prescribing practice.</p> <p>Methods</p> <p>Data was collected through nine focus group interviews with a total of 39 GPs and 20 tutors. Transcripts from the interviews were analyzed by two researchers according to a procedure for thematic content analysis.</p> <p>Results</p> <p>A shared understanding of the complex decision-making involved in prescribing in general practice was reported by both GPs and tutors as essential for an open discussion in the CME groups. Tutors experienced that CME groups differed regarding structure and atmosphere, and in some groups it was a challenge to run the scheme as planned. Individual feedback motivated GPs to reflect on and to improve their prescribing practice, though feedback reports could cause distress if the prescribing practice was unfavourable. Explanations for inappropriate prescriptions were lack of knowledge, factors associated with patients, the GP's background, the practice, and other health professionals or health care facilities.</p> <p>Conclusions</p> <p>GPs and tutors experienced peer group academic detailing as a suitable method to discuss and learn more about pharmacotherapy. An important outcome for GPs was being more reflective about their prescriptions. Disclosure of inappropriate prescribing can cause distress in some doctors, and tutors must be prepared to recognise and manage such reactions.</p

Alanine Racemase Mutants of Burkholderia pseudomallei and Burkholderia mallei and Use of Alanine Racemase as a Non-Antibiotic-Based Selectable Marker

Burkholderia pseudomallei and Burkholderia mallei are category B select agents and must be studied under BSL3 containment in the United States. They are typically resistant to multiple antibiotics, and the antibiotics used to treat B. pseudomallei or B. mallei infections may not be used as selective agents with the corresponding Burkholderia species. Here, we investigated alanine racemase deficient mutants of B. pseudomallei and B. mallei for development of non-antibiotic-based genetic selection methods and for attenuation of virulence. The genome of B. pseudomallei K96243 has two annotated alanine racemase genes (bpsl2179 and bpss0711), and B. mallei ATCC 23344 has one (bma1575). Each of these genes encodes a functional enzyme that can complement the alanine racemase deficiency of Escherichia coli strain ALA1. Herein, we show that B. pseudomallei with in-frame deletions in both bpsl2179 and bpss0711, or B. mallei with an in-frame deletion in bma1575, requires exogenous d-alanine for growth. Introduction of bpsl2179 on a multicopy plasmid into alanine racemase deficient variants of either Burkholderia species eliminated the requirement for d-alanine. During log phase growth without d-alanine, the viable counts of alanine racemase deficient mutants of B. pseudomallei and B. mallei decreased within 2 hours by about 1000-fold and 10-fold, respectively, and no viable bacteria were present at 24 hours. We constructed several genetic tools with bpsl2179 as a selectable genetic marker, and we used them without any antibiotic selection to construct an in-frame ΔflgK mutant in the alanine racemase deficient variant of B. pseudomallei K96243. In murine peritoneal macrophages, wild type B. mallei ATCC 23344 was killed much more rapidly than wild type B. pseudomallei K96243. In addition, the alanine racemase deficient mutant of B. pseudomallei K96243 exhibited attenuation versus its isogenic parental strain with respect to growth and survival in murine peritoneal macrophages

Understanding Project Champions’ Ability to Gain Intra-Organizational Commitment for Environmental Projects

A key enabler of environmental projects is the ability of the project champion to gain commitment to the project from other stakeholders in his or her organization. This paper develops a model of commitment-gaining success that is based on intra-organizational influence theory. The model also includes the project payback, customer pressure, government regulation, top management support and the project champion’s position in the organizational hierarchy. The model was tested using survey data from 241 environmental professionals describing their attempts to gain the buy-in of purchasing managers, operations managers, industrial engineers and others for environmental projects. The results (obtained from hierarchical regression analysis) show that intra-organizational commitment is positively associated with the project champion’s influence behavior—in particular, the champion’s use of three influence tactics (inspirational appeals, consultation and rational persuasion) and avoidance of a fourth tactic (ingratiation). Commitment is also positively associated with project payback and with top management support for the environment and negatively associated with environmental regulation. The paper contributes to the OM knowledge base of environmental project implementation by bringing new theory to bear on the topic, by focusing on individual-level, rather than organization-level, variables and by taking a confirmatory, large sample approach which complements extant exploratory research. In addition, the paper contributes to the OM field by evaluating various antecedents to cross-functional integration. The results also provide specific guidance to those who champion environmental projects within their companies

Doxycycline for Malaria Chemoprophylaxis and Treatment: Report from the CDC Expert Meeting on Malaria Chemoprophylaxis

Doxycycline, a synthetically derived tetracycline, is a partially efficacious causal prophylactic (liver stage of Plasmodium) drug and a slow acting blood schizontocidal agent highly effective for the prevention of malaria. When used in conjunction with a fast acting schizontocidal agent, it is also highly effective for malaria treatment. Doxycycline is especially useful as a prophylaxis in areas with chloroquine and multidrug-resistant Plasmodium falciparum malaria. Although not recommended for pregnant women and children < 8 years of age, severe adverse events are rarely reported for doxycycline. This report examines the evidence behind current recommendations for the use of doxycycline for malaria and summarizes the available literature on its safety and tolerability