Medicine and Health Sciences Commons^™

A Review Of Baobab (Adansonia Digitata) Products: Effect Of Processing Techniques, Medicinal Properties And Uses, Donatien Kabore, Hagrétou Sawadogo-Lingani, Bréhima Diawara, Clarise Compaoré, Mamoudou H. Dicko Prof., Mogens Jacobsen

Pr. Mamoudou H. DICKO, PhD

A general literature review including the effect of processing techniques, medicinal value and uses of baobab tree is reported in this manuscript. Baobab tree has multi-purpose uses, as it produces food and non-food products such as medicines, fuel, timber, fodder. Every part of the baobab tree is reported to be useful. The seeds, leaves, roots, flowers, fruit pulp and bark of baobab are edible. Baobab leaves are used in the preparation of soup. Seeds are used as a thickening agent in soups, but they can be fermented and used as a flavouring agent or roasted and eaten as snacks. The …

Identifying Characteristics Of Effective Small Group Learning Valued By Medical Students And Facilitators, Diana T. Robillard, Laura M. Spring, Susan J. Pasquale, Judith A. Savageau

Judith A. Savageau

Background: Small group teaching is an important part of undergraduate medical education, providing the ideal setting for learners to clarify misunderstandings, test hypotheses and evaluate ideas. Many schools undergoing curriculum reform have increased the time students spend in small group learning. However, there is an overall paucity of literature examining case-based small group sessions in medical school.

Objective: This study was designed to examine student and facilitator perceptions of effective case-based small group teaching in the pre-clinical years and compare results in order to identify similarities and differences and identify key areas of disconnect so that the small …

Improving Prenatal Education In A Health Center: A Pilot Study, Marcy Keddy Boucher, Hugh Silk, Judith A. Savageau, Katharine C. Barnard, Mary Flynn

Judith A. Savageau

Background: Currently, the timing and variety of health education topics that are covered during prenatal visits are decided upon by the individual physician caring for the patient. Consequently, some patients do not gain exposure to important subject matter that could potentially improve their satisfaction and pregnancy outcomes. Previously reported studies have found evidence that improved patient education may increase rates of breastfeeding (as well as duration), seat belt use during pregnancy, and decrease preterm low birth weight infants. In addition, one study has shown that when prenatal visits are targeted to specific objectives, the number of prenatal visits can …

Map Kinases Couple Hindbrain-Derived Catecholamine Signals To Hypothalamic Adrenocortical Control Mechanisms During Glycemia-Related Challenges, Arshad M. Khan, Kimberly L. Kaminski, Graciela Sanchez-Watts, Todd A. Ponzio, J. Brent Kuzmiski, Jaideep S. Bains, Alan G. Watts

Arshad M. Khan, Ph.D.

No abstract provided.

Site-Directed Mutations In The C-Terminal Extension Of Human Αb-Crystallin Affect Chaperone Function And Block Amyloid Fibril Formation, T. M. Treweek, Heath Ecroyd, D. M. Williams, S. Meehan, J. A. Carver, M. J. Walker

Heath Ecroyd

Alzheimer’s, Parkinson’s and Creutzfeldt-Jakob disease are associated with inappropriate protein deposition and ordered amyloid fibril assembly. Molecular chaperones, including αBcrystallin, play a role in the prevention of protein deposition. A series of site-directed mutants of the human molecular chaperone, αB-crystallin, were constructed which focused on the flexible C-terminal extension of the protein. We investigated the structural role of this region as well as its role in the chaperone function of αB-crystallin under different types of protein aggregation, i.e. disordered amorphous aggregation and ordered amyloid fibril assembly. It was found that mutation of lysine and glutamic acid residues in the C-terminal …

Hallucination Proneness, Schizotypy And Meta-Cognition, John Stirling, Emma Barkus, Shon Lewis

Emma Barkus

Disordered or maladaptive meta-cognitive processing appears to be a prominent feature for some individuals with a diagnosis of schizophrenia. We sought to establish whether healthy individuals distinguished either in terms hallucination proneness (HP) or level of schizotypy could also be differentiated on the sub-scales of the Meta-cognitions Questionnaire (MCQ), or a modified version of it in which items about worry were replaced with items specifically related to thinking. A total of 106 healthy volunteers completed the Oxford and Liverpool Inventory of Feelings and Experiences and Launay-Slade hallucination scale, the Schizotypal Personality Questionnaire and two versions of the MCQ: the original …

Ecstasy (Mdma) And Its Relationship With Self Report Depression, Anxiety And Schizotypy, Lisa Woods, Emma Barkus

Emma Barkus

Abstract. Aims: The relationship between ecstasy and affective psychological symptoms are still subject to debate. We aimed to examine the relationship between Ecstasy use and self-report depression, anxiety and schizotypy. Design: Data were collected via structured remote self-report questionnaires. Participants: Participants were split into three groups: a control group with no ecstasy use, a light ecstasy user group (<50 >times), and a heavy ecstasy user group (>50 times). Measurements: Amount and patterns of ecstasy use were recorded, the Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) measured depression and anxiety respectively, and schizotypal traits were measured using the …

Understanding And Using Advanced Statistics, Jeremy Foster, Emma Barkus, Christian Yavorsky

Emma Barkus

The spread of sophisticated computer packages and the machinery on which to run them has meant that procedures which were previously only available to experienced researchers with access to expensive machines and research students can now be carried out in a few seconds by almost every undergraduate. Understanding and Using Advanced Statistics provides the basis for gaining an understanding of what these analytic procedures do, when they should be used, and what the results provided signify. This comprehensive textbook guides students and researchers through the transition from simple statistics to more complex procedures with accessible language and illustration.

Cannabis-Induced Psychosis-Like Experiences Are Associated With High Schizotypy, Emma Barkus, John Stirling, Richard Hopkins, Shon Lewis

Emma Barkus

OBJECTIVE: Recent studies have suggested that cannabis use is a risk factor for developing schizophrenia. We tested the hypothesis that cannabis use increases the likelihood of psychosis-like experiences in non-clinical participants who scored highly on a measure of schizotypy. METHOD: The psychological effects of cannabis were assessed in 137 healthy individuals (76% female, mean age 22 years) using a newly developed questionnaire concerned with subjective experiences of the drug: the Cannabis Experiences Questionnaire. The questionnaire has three subscales: Pleasurable Experiences, Psychosis-Like Experiences and After-Effects. Respondents also completed the brief Schizotypal Personality Questionnaire. RESULTS: Cannabis use was reported by 72% of …

Cannabis-Induced Psychotic-Like Experiences Are Predicted By High Schizotypy. Confirmation Of Preliminary Results In A Large Cohort., John Stirling, Emma Barkus, L Nabosi, S Irshad, G Roemer, B Schreudergoidheijt, Shon Lewis

Emma Barkus

Background: Cannabis use has been identified as a possible risk factor for developing schizophrenia. In a previous paper we reported preliminary evidence that cannabis use increases the likelihood of psychosis-like experiences in non-clinical respondents who scored highly on a measure of schizotypy. We now present findings from pooled data from 3 new follow-up studies comprising a sample of 477 respondents, of whom 332 reported using cannabis at least once. Sampling and Methods: As in our previous study, the psychological effects of cannabis were assessed with the Cannabis Experiences Questionnaire, from which 3 subscales can be derived; encompassing pleasurable experiences, psychosis-like …

Suggestibility, Dissociation And Positive Schizotypy, Emma Barkus, John Stirling, John Cavill

Emma Barkus

Abstract. 94 participants, drawn from a parent sample of 1206 individuals who had previously taken part in an assessment of the factor structure of the Oxford-Liverpool Inventory of Feelings and Experiences (O-LIFE), were designated into groups differentiated in terms of low, moderate or high levels of positive schizotypy. All also completed the dissociative experiences scale (DES) and the Inventory of Suggestibility (IS). Our findings suggest that higher reported levels of dissociative experiences and higher suggestibility both independently predict higher scores of positive schizotypy, although suggestibility appears to be a stronger predictor than dissociation.

Schizotypy And Psychosis-Like Experiences From Recreational Cannabis In A Non-Clinical Sample, Emma Barkus, Shon Lewis

Emma Barkus

Background. The relationship between cannabis use and psychosis is still a matter for debate. Accounting for the individual differences in subjective experiences to recreational cannabis use in the general population may hold some clues to the aetiological relationship between cannabis and psychotic symptoms. We hypothesized that schizotypy would account for the individual differences in subjective experiences after cannabis use but not in patterns of use. Method. In a sample of 532 young people who had used cannabis at least once, we examined the relationship between the Cannabis Experiences Questionnaire (CEQ) and the Schizotypal Personality Questionnaire (SPQ). Additionally, we examined the …

Distress And Metacognition In Psychosis Prone Individuals: Comparing High Schizotypes To The At-Risk Mental State, Emma Barkus, John Stirling, Paul French, Anthony Morrison, Richard Bentall, Shon Lewis

Emma Barkus

Both schizotypy and at-risk mental states (ARMS: prodromal states) define individuals at risk for psychotic symptoms. However, the relationship between the 2 is unclear. ARMS individuals are, by definition, help-seeking and therefore at greater risk. We tested whether high schizotypes and ARMS exist along the same continuum by examining maladaptive metacognitions and distress. About 95 healthy volunteers (39% male; mean age, 22.8 years) completed the Schizotypal Personality Questionnaire, the Launay-Slade Hallucinations Scale, Metacognitions Questionnaire (MCQ), and the General Health Questionnaire, and 58 help seeking individuals with ARMS status (41% male; mean age, 22.2 years) completed the Metacognitions Questionnaire and General …

Personality And Cannabis Use, Emma Barkus

Emma Barkus

Cannabis is one of the most widely used illegal substances in the world. Its use has been reported to be over-represented in many psychiatric conditions and has frequently been found to predate the onset of psychiatric symptoms. However, cannabis may also have detrimental effects on the general population. Factors that predict the onset of use are receiving increased attention to aid in identifying groups of young people who may be more prone to consume cannabis. Personality traits may be one such factor as they are readily identifiable and offer information that can be used for improved targeting of educational material …

Midwifery And The Context Of Care: Is It Possible To Be 'Woman Centred'?, Moira Williamson, Lindsey Harrison

Moira Williamson

Title: Midwifery and the context of care: Is it impossible to be ‘woman centred’? Dr Moira Williamson, School of Nursing, Midwifery and Indigenous Health, University of Wollongong, Northfields Avenue, Wollongong NSW 2522, Australia, ph. +61 2 4221 3381, email: moiraw@uow.edu.au Dr Lindsey Harrison, School of Health Sciences, University of Wollongong Background: Findings from a qualitative study show that the context of care can inhibit midwives’ provision of woman centred care; especially impacted is their ability to provide culturally appropriate care. Aim of the Study: The aims of the study were to gain an understanding of midwives’ concepts of culture and …

Workforce Issues, Skill Mix, Maternity Services And The Enrolled Nurse : A Discussion, Moira Williamson, Avon Strahle

Moira Williamson

New South Wales (NSW) is experiencing a shortage of registered midwives. Currently midwives are being actively recruited for 125 metropolitan and 45 rural positions in area health services across the state. This shortage of registered midwives is occurring not only in NSW but also throughout Australia, and has also been reported internationally (McKenna & Hasson, 2002; Keeney et al. 2005). In an attempt to address the ongoing shortage of registered nurses and midwives the NSW Health Department has proposed that a skill mix of 80% registered nurses or midwives to 20% enrolled nurses be implemented within hospitals. This initiative will …

Child Birth: Don't Forget The Fathers, Moira Williamson

Moira Williamson

Fathers are often forgotten when a new baby comes into a family. But men face many challenges in the early months of fatherhood as they come to terms with their new or expanded role. And they need more support. UOW Senior Lecturer and Master of Science (Midwifery) Co-ordinator Moira Williamson and colleagues Professor Carol McVeigh from Massey University (NZ) and Mercy Baafi, Midwifery Manager (Education) at Wollongong Hospital, researched the impact of parenthood with 128 new fathers. MOIRA WILLIAMSON prepared this Opinion column, based on their research.

Phaseolus Beans: Impact On Glycaemic Response And Chronic Disease Risk In Human Subjects, Andrea M. Hutchins, Donna M. Winham, Sharon V. Thompson

Donna Winham

Consumption of Phaseolus vulgaris bean species such as pinto, black, navy or kidney may be beneficial in the prevention and treatment of chronic diseases. In particular, conditions that are promoted by increased glycaemic stress (hyperglycaemia and hyperinsulinaemia) including diabetes, CVD and cancer seem to be reduced in individuals who eat more of these beans. The present paper discusses the influence of P. vulgaris species on glycaemic response and the impact that relationship may have on the risk of developing diabetes, CVD and cancer.

Associations Of Daily Eating Episodes, And Eating Away-From-Home With Blood Level Of Total Cholesterol, Yunsheng Ma, Elizabeth R. Bertone-Johnson, Edward J. Stanek, Dr. Nancy L. Cohen, Ira S. Ockene

Nancy L. Cohen

The objective of this investigation is to describe the associations of number of eating episodes and proportion of meals eaten away from home with total serum cholesterol. Data from 499 participants, recruited from a health maintenance organization in central Massachusetts, aged 20-70, were used for this analysis. Dietary information and total blood cholesterol were obtained at five sampling points (baseline and four consecutive quarters) during the one-year follow-up. A cross-sectional study was conducted. The results from the study do not support the hypothesis that the number of eating episodes per day is associated with total blood cholesterol. However, we noted …

Nitric Oxide-Mediated Inhibition Of Hdm2-P53 Binding, Christopher Schonhoff, Marie-Claire Daou, Stephen Jones, Celia Schiffer, Alonzo Ross

Celia A. Schiffer

It has become increasingly evident that nitric oxide exerts its effects, in part, by S-nitrosylation of cysteine residues. We tested in vitro whether nitric oxide may indirectly control p53 by S-nitrosylation and inactivation of the p53 negative regulator, Hdm2. Treatment of Hdm2 with a nitric oxide donor inhibits Hdm2-p53 binding, a critical step in Hdm2 regulation of p53. The presence of excess amounts of cysteine or dithiothreitol blocks this inhibition of binding. Moreover, nitric oxide inhibition of Hdm2-p53 binding was found to be reversible. Sulfhydryl sensitivity and reversibility are consistent with nitrosylation. Finally, we have identified a critical cysteine residue …

Co-Evolution Of Nelfinavir-Resistant Hiv-1 Protease And The P1-P6 Substrate, Madhavi Kolli, Stephane Lastere, Celia Schiffer

Celia A. Schiffer

The selective pressure of the competitive protease inhibitors causes both HIV-1 protease and occasionally its substrates to evolve drug resistance. We hypothesize that this occurs particularly in substrates that protrude beyond the substrate envelope and contact residues that mutate in response to a particular protease inhibitor. To validate this hypothesis, we analyzed substrate and protease sequences for covariation. Using the chi2 test, we show a positive correlation between the nelfinavir-resistant D30N/N88D protease mutations and mutations at the p1-p6 cleavage site as compared to the other cleavage sites. Both nelfinavir and the substrate p1-p6 protrude beyond the substrate envelope and contact …

Crystal Structure Of Lysine Sulfonamide Inhibitor Reveals The Displacement Of The Conserved Flap Water Molecule In Human Immunodeficiency Virus Type 1 Protease, Madhavi Nalam, Anik Peeters, Tim Jonckers, Inge Dierynck, Celia Schiffer

Celia A. Schiffer

Human immunodeficiency virus type 1 (HIV-1) protease has been continuously evolving and developing resistance to all of the protease inhibitors. This requires the development of new inhibitors that bind to the protease in a novel fashion. Most of the inhibitors that are on the market are peptidomimetics, where a conserved water molecule mediates hydrogen bonding interactions between the inhibitors and the flaps of the protease. Recently a new class of inhibitors, lysine sulfonamides, was developed to combat the resistant variants of HIV protease. Here we report the crystal structure of a lysine sulfonamide. This inhibitor binds to the active site …

Structural Basis For Coevolution Of A Human Immunodeficiency Virus Type 1 Nucleocapsid-P1 Cleavage Site With A V82a Drug-Resistant Mutation In Viral Protease, Moses Prabu-Jeyabalan, Ellen A. Nalivaika, Nancy M. King, Celia A. Schiffer

Celia A. Schiffer

Maturation of human immunodeficiency virus (HIV) depends on the processing of Gag and Pol polyproteins by the viral protease, making this enzyme a prime target for anti-HIV therapy. Among the protease substrates, the nucleocapsid-p1 (NC-p1) sequence is the least homologous, and its cleavage is the rate-determining step in viral maturation. In the other substrates of HIV-1 protease, P1 is usually either a hydrophobic or an aromatic residue, and P2 is usually a branched residue. NC-p1, however, contains Asn at P1 and Ala at P2. In response to the V82A drug-resistant protease mutation, the P2 alanine of NC-p1 mutates to valine …

New Approaches To Hiv Protease Inhibitor Drug Design Ii: Testing The Substrate Envelope Hypothesis To Avoid Drug Resistance And Discover Robust Inhibitors, Madhavi Nalam, Celia Schiffer

Celia A. Schiffer

PURPOSE OF REVIEW: Drug resistance results when the balance between the binding of inhibitors and the turnover of substrates is perturbed in favor of the substrates. Resistance is quite widespread to the HIV-1 protease inhibitors permitting the protease to process its 10 different substrates. This processing of the substrates permits the virus HIV-1 to mature and become infectious. The design of HIV-1 protease inhibitors that closely fit within the substrate-binding region is proposed to be a strategy to avoid drug resistance. RECENT FINDINGS: Cocrystal structures of HIV-1 protease with its substrates define an overlapping substrate-binding region or substrate envelope. Novel …

Mechanism Of Substrate Recognition By Drug-Resistant Human Immunodeficiency Virus Type 1 Protease Variants Revealed By A Novel Structural Intermediate, Moses Prabu-Jeyabalan, Ellen A. Nalivaika, Keith Romano, Celia A. Schiffer

Celia A. Schiffer

Human immunodeficiency virus type 1 (HIV-1) protease processes and cleaves the Gag and Gag-Pol polyproteins, allowing viral maturation, and therefore is an important target for antiviral therapy. Ligand binding occurs when the flaps open, allowing access to the active site. This flexibility in flap geometry makes trapping and crystallizing structural intermediates in substrate binding challenging. In this study, we report two crystal structures of two HIV-1 protease variants bound with their corresponding nucleocapsid-p1 variant. One of the flaps in each of these structures exhibits an unusual "intermediate" conformation. Analysis of the flap-intermediate and flap-closed crystal structures reveals that the intermonomer …

Point Mutants Of Ehec Intimin That Diminish Tir Recognition And Actin Pedestal Formation Highlight A Putative Tir Binding Pocket, Hui Liu, Padhma Radhakrishnan, Loranne Magoun, Moses Prabu-Jeyabalan, Kenneth Campellone, Pamela Savage, Feng He, Celia Schiffer, John Leong

Celia A. Schiffer

Attachment to host cells by enterohaemorrhagic Escherichia coli (EHEC) is associated with the formation of a highly organized cytoskeletal structure containing filamentous actin, termed an attaching and effacing (AE) lesion. Intimin, an outer membrane protein of EHEC, is required for the formation of AE lesions, as is Tir, a bacterial protein that is translocated into the host cell to function as a receptor for intimin. We established a yeast two-hybrid assay for intimin-Tir interaction and, after random mutagenesis, isolated 24 point mutants in intimin, which disrupted Tir recognition in this system. Analysis of 11 point mutants revealed a correlation between …

Structural And Thermodynamic Basis For The Binding Of Tmc114, A Next-Generation Human Immunodeficiency Virus Type 1 Protease Inhibitor, Nancy King, Moses Prabu-Jeyabalan, Ellen Nalivaika, Piet Wigerinck, Marie-Pierre De Bethune, Celia Schiffer

Celia A. Schiffer

TMC114, a newly designed human immunodeficiency virus type 1 (HIV-1) protease inhibitor, is extremely potent against both wild-type (wt) and multidrug-resistant (MDR) viruses in vitro as well as in vivo. Although chemically similar to amprenavir (APV), the potency of TMC114 is substantially greater. To examine the basis for this potency, we solved crystal structures of TMC114 complexed with wt HIV-1 protease and TMC114 and APV complexed with an MDR (L63P, V82T, and I84V) protease variant. In addition, we determined the corresponding binding thermodynamics by isothermal titration calorimetry. TMC114 binds approximately 2 orders of magnitude more tightly to the wt enzyme …

Lack Of Synergy For Inhibitors Targeting A Multi-Drug-Resistant Hiv-1 Protease, Nancy King, Laurence Melnick, Moses Prabu-Jeyabalan, Ellen Nalivaika, Shiow-Shong Yang, Yun Gao, Xiaoyi Nie, Charles Zepp, Donald Heefner, Celia Schiffer

Celia A. Schiffer

The three-dimensional structures of indinavir and three newly synthesized indinavir analogs in complex with a multi-drug-resistant variant (L63P, V82T, I84V) of HIV-1 protease were determined to approximately 2.2 A resolution. Two of the three analogs have only a single modification of indinavir, and their binding affinities to the variant HIV-1 protease are enhanced over that of indinavir. However, when both modifications were combined into a single compound, the binding affinity to the protease variant was reduced. On close examination, the structural rearrangements in the protease that occur in the tightest binding inhibitor complex are mutually exclusive with the structural rearrangements …

Hydrophobic Sliding: A Possible Mechanism For Drug Resistance In Human Immunodeficiency Virus Type 1 Protease, Jennifer Foulkes-Murzycki, Walter Scott, Celia Schiffer

Celia A. Schiffer

Hydrophobic residues outside the active site of HIV-1 protease frequently mutate in patients undergoing protease inhibitor therapy; however, the mechanism by which these mutations confer drug resistance is not understood. From analysis of molecular dynamics simulations, 19 core hydrophobic residues appear to facilitate the conformational changes that occur in HIV-1 protease. The hydrophobic core residues slide by each other, exchanging one hydrophobic van der Waal contact for another, with little energy penalty, while maintaining many structurally important hydrogen bonds. Such hydrophobic sliding may represent a general mechanism by which proteins undergo conformational changes. Mutation of these residues in HIV-1 protease …

Viability Of A Drug-Resistant Human Immunodeficiency Virus Type 1 Protease Variant: Structural Insights For Better Antiviral Therapy, Moses Prabu-Jeyabalan, Ellen A. Nalivaika, Nancy M. King, Celia A. Schiffer

Celia A. Schiffer

Under the selective pressure of protease inhibitor therapy, patients infected with human immunodeficiency virus (HIV) often develop drug-resistant HIV strains. One of the first drug-resistant mutations to arise in the protease, particularly in patients receiving indinavir or ritonavir treatment, is V82A, which compromises the binding of these and other inhibitors but allows the virus to remain viable. To probe this drug resistance, we solved the crystal structures of three natural substrates and two commercial drugs in complex with an inactive drug-resistant mutant (D25N/V82A) HIV-1 protease. Through structural analysis and comparison of the protein-ligand interactions, we found that Val82 interacts more …