Most of the 1.1 million women who deliver by cesarean in the United States each year have an uncomplicated recovery. However, severe pain resistant to standard multimodal therapy within the first ...days after surgery is associated with an increased risk for prolonged pain and opioid use. The best outpatient management for parturients with severe resistant early onset pain is not known.
We performed a prospective, double-blind, placebo-controlled, randomized trial of up to 12 weeks of outpatient treatment with gabapentin to evaluate its effectiveness to facilitate opioid cessation in women with at least 2 reports of severe pain during the immediate postpartum period resistant to standard multimodal pain management. Time to opioid cessation was the primary outcome. Time to pain resolution; time to discontinuation of gabapentin, acetaminophen, and ibuprofen; time to self-reported recovery; and National Institute of Health Patient-Reported Outcomes System (PROMIS) surveys for anxiety, depression, fatigue, and physical function were assessed as secondary outcomes.
There was no difference in time to opioid cessation between patients who were randomly assigned to be treated with gabapentin (Kaplan-Meier estimated median of 2 25th-75th percentiles of 1-3 weeks, n = 35) versus those who were treated with placebo (2 1-3 weeks, n = 35). The hazard ratio was 1.1 (95% confidence interval CI, 0.67-1.8), P = .65. There were no differences in any secondary end points between the study groups.
Outpatient supplementation with gabapentin did not reduce time to opioid cessation, pain, anxiety, depression, fatigue, or improve physical function in women with severe pain after cesarean delivery. Gabapentin should not be routinely added to the standard outpatient multimodal regimen of ibuprofen, acetaminophen, and opioids.
Purpose
– This qualitative, exploratory study uses constructs from the theory of planned behaviour (TPB) and construct variables from literature, as a basis to ascertain similarities and differences ...in the behaviour by business undergraduates (UGs) and postgraduates (PGs) of mobile apps and the purpose of this paper is to suggest implications for consumer behaviour theory and marketing practice for the two groups of students.
Design/methodology/approach
– Literature informed us of the paucity of research on the relationship between behavioural theory and mobile apps usage in the Asia region. An exploratory and interpretivist approach, with thematic analysis, was employed to aid in data processing.
Findings
– The investigative outcomes highlighted more similarities than dissimilarities in terms of perceived attitude (e.g. mood, ethical guilt, familiarity, addiction) and more differences in perceived subjective norms (e.g. family, friends, classmates and teammates) and perceived users’ behavioural control (e.g. promotional inducements, self-confidence) towards the usage of mobile apps exhibited by two different sets of data.
Research limitations/implications
– Homogeneity of participants, small sample size and generalisability of results were the main concern, hence, it warrants further research. In addition a cross-cultural comparison would be beneficial which might generate more meaningful results.
Practical implications
– The research, albeit exploratory, serves as a guide for marketers and apps content providers to focus on usability of features and functions of apps as well as credibility, social context, timing, location, excitement of advertisements and promotional messages especially when marketing to the 18-30-age group. The research also shows that practitioners should be nuanced in their appeals to UGs and PGs.
Originality/value
– Despite the provision of numerous mobile apps, this study, using the constructs of the TPB as a basis, offers a new insight into the reasons for, and usage of, specific and top popular apps (e.g. FB, Whatsapps and WeChat) Malaysian students used which reflects a varied behavioural dimension as opposed to planned behaviour.
Teneurins are ancient metazoan cell adhesion receptors that control brain development and neuronal wiring in higher animals. The extracellular C terminus binds the adhesion GPCR Latrophilin, forming ...a trans-cellular complex with synaptogenic functions. However, Teneurins, Latrophilins, and FLRT proteins are also expressed during murine cortical cell migration at earlier developmental stages. Here, we present crystal structures of Teneurin-Latrophilin complexes that reveal how the lectin and olfactomedin domains of Latrophilin bind across a spiraling beta-barrel domain of Teneurin, the YD shell. We couple structure-based protein engineering to biophysical analysis, cell migration assays, and in utero electroporation experiments to probe the importance of the interaction in cortical neuron migration. We show that binding of Latrophilins to Teneurins and FLRTs directs the migration of neurons using a contact repulsion-dependent mechanism. The effect is observed with cell bodies and small neurites rather than their processes. The results exemplify how a structure-encoded synaptogenic protein complex is also used for repulsive cell guidance.
Display omitted
•Crystal structures reveal binding site for Latrophilin on the Teneurin YD shell•A ternary Latrophilin-Teneurin-FLRT complex forms in vitro and in vivo•Latrophilin controls cortical migration by binding to Teneurins and FLRTs•Latrophilin elicits repulsion of cortical cell bodies/small neurites but not axons
3D structures reveal how Latrophilin binds across the Teneurin protein and enable modeling of simultaneous FLRT binding. del Toro et al. show that this trimeric complex is important not only during synapse formation but also in earlier stages of development, where it guides the migration of young neurons by providing repulsive signals.
Purpose: The purpose of this paper is to investigate two areas of interest: first, to determine business student customer satisfiers that could be contributors to students' current and predicted ...retention in a higher educational institution (HEI) and second, to use these satisfiers to inform HEI marketing planning. Design/Methodology/Approach: The survey used 10 per cent of the sampling frame from the faculty total business students population. Descriptive statistics and correlation were employed to describe and measure the relationship between the teaching and non-teaching antecedents of student satisfaction and their five constructs (academic experience, teaching quality, campus life, facilities and placement support) and current and intended retention. Standard multiple regressions were run to measure the ß and significant values of the composite variables as stated. Findings: Quantitative results revealed that students were most satisfied with academic experience and it was also the most dominant predictor of students' retention. Other elements such as quality teaching, facilities and internship, though important for student satisfaction, were not predictors of retention. Research Limitations/Implications: Findings based on one Malaysian institution could not be used as a representation of other institutions either locally or internationally. Practical Implications: Suggestions are made as to how HEIs can defend and safeguard their existing and future position by giving maximum attention to both "hard" and "soft" student satisfiers which would add customer value and strengthen their competitive position. Originality/Value: Based on teaching and non-teaching antecedents and constructs, enable HEIs to predict retention and so inform marketing planning in a highly competitive higher education environment.
Membranes in cells have defined distributions of lipids in each leaflet, controlled by lipid scramblases and flip/floppases. However, for some intracellular membranes such as the endoplasmic ...reticulum (ER) the scramblases have not been identified. Members of the TMEM16 family have either lipid scramblase or chloride channel activity. Although TMEM16K is widely distributed and associated with the neurological disorder autosomal recessive spinocerebellar ataxia type 10 (SCAR10), its location in cells, function and structure are largely uncharacterised. Here we show that TMEM16K is an ER-resident lipid scramblase with a requirement for short chain lipids and calcium for robust activity. Crystal structures of TMEM16K show a scramblase fold, with an open lipid transporting groove. Additional cryo-EM structures reveal extensive conformational changes from the cytoplasmic to the ER side of the membrane, giving a state with a closed lipid permeation pathway. Molecular dynamics simulations showed that the open-groove conformation is necessary for scramblase activity.
Very long chain fatty acids (VLCFAs) are essential building blocks for the synthesis of ceramides and sphingolipids. The first step in the fatty acid elongation cycle is catalyzed by the 3-keto ...acyl-coenzyme A (CoA) synthases (in mammals, ELOVL elongases). Although ELOVLs are implicated in common diseases, including insulin resistance, hepatic steatosis and Parkinson's, their underlying molecular mechanisms are unknown. Here we report the structure of the human ELOVL7 elongase, which comprises an inverted transmembrane barrel surrounding a 35-Å long tunnel containing a covalently attached product analogue. The structure reveals the substrate-binding sites in the narrow tunnel and an active site deep in the membrane. We demonstrate that chain elongation proceeds via an acyl-enzyme intermediate involving the second histidine in the canonical HxxHH motif. The unusual substrate-binding arrangement and chemistry suggest mechanisms for selective ELOVL inhibition, relevant for diseases where VLCFAs accumulate, such as X-linked adrenoleukodystrophy.
Protein N-glycosylation is a widespread post-translational modification. The first committed step in this process is catalysed by dolichyl-phosphate N-acetylglucosamine-phosphotransferase DPAGT1 ...(GPT/E.C. 2.7.8.15). Missense DPAGT1 variants cause congenital myasthenic syndrome and disorders of glycosylation. In addition, naturally-occurring bactericidal nucleoside analogues such as tunicamycin are toxic to eukaryotes due to DPAGT1 inhibition, preventing their clinical use. Our structures of DPAGT1 with the substrate UDP-GlcNAc and tunicamycin reveal substrate binding modes, suggest a mechanism of catalysis, provide an understanding of how mutations modulate activity (thus causing disease) and allow design of non-toxic “lipid-altered” tunicamycins. The structure-tuned activity of these analogues against several bacterial targets allowed the design of potent antibiotics for Mycobacterium tuberculosis, enabling treatment in vitro, in cellulo and in vivo, providing a promising new class of antimicrobial drug.
Display omitted
•Structures of DPAGT1 with UDP-GlcNAc and tunicamycin reveal mechanisms of catalysis•DPAGT1 mutations in patients with glycosylation disorders modulate DPAGT1 activity•Structures, kinetics and biosynthesis reveal role of lipid in tunicamycin•Lipid-altered, tunicamycin analogues give non-toxic antibiotics against TB
Structural insights into tunicamycin’s toxic interactions with the human N-linked glycosylation pathway allows the identification of non-toxic antibiotics effective against tuberculosis in mice
Purpose
The purpose of this paper is to investigate how students in a Malaysian context, as a result of their experience of a Higher Education Institution (HEI) undergraduate teaching and learning ...experience in the subject of Marketing, perceive the knowledge, skills and competencies required of a practicing marketer and, conversely, what curriculum developers need to do if there is a “shortfall”.
Design/methodology/approach
Based on a total sample of a UG student population from an Accountancy, Finance and Business Faculty, the primarily descriptive, positivist, cross-sectional study used inferential statistics to measure the relationship between the four components of marketing knowledge, skills and competencies (the marketing mix, performance, social and emotional competencies, and responsible decision making).
Findings
Quantitative results revealed that all student perceptions of the requirements to be a “fit for purpose” marketer were highly correlated with requirements from the literature, subject benchmarks and practice with few exemptions.
Research limitations/implications
The findings are based on one institution. Moreover, knowledge, skills and competency requirements by students’ level of study and practitioner experience may vary by type of HEI, organisation and geographic location.
Practical implications
Recommendations are made for curriculum development to address both employability and career development, particularly in terms of interdisciplinary co-operation and the teaching and learning of concepts.
Originality/value
Using the student perceptions of the requirements for being a practicing marketer, HEIs can adjust/add to their curriculum by comparing these to documented sources from academia and practice and by making any necessary adjustments by course of study.
Purpose
The purpose of this study was to examine the influence of adopted corporate social responsibility (CSR) constructs, which include economic, legal, ethical and philanthropic responsibilities, ...on the intended buying behaviour of Malaysian consumers. The study also aims to investigate the perceived value of whether the consumers considered an organisation’s CSR initiatives before deciding any purchase of products or services.
Design/methodology/approach
An online Google form survey successfully obtained 295 usable responses through a snowballing and networking approach. Statistical analyses such as Pearson correlation, ANOVA and standard multiple regression were used to examine the correlation and the strength of relationship, as well as the prediction between the CSR attributes and their impact on consumer buying behaviour.
Findings
The results represented a significant positive association between all the four constructs (social, ethical, legal and philanthropic) and consumer intended buying behaviour. These constructs also significantly contributed to the prediction of consumer behaviour towards the CSR initiatives. Conversely, the demographic profile of consumers had no effect on the relationship between CSR and consumer buying behaviour.
Research limitations/implications
Examining basic concepts of CSR awareness and understanding might add to the flavour and rigour of this study, which future research should consider. The positivist approach of the current research could be supplemented with a more interactive qualitative in-depth study investigating why and how consumers behave.
Practical implications
The implication for Malaysian companies is that it is imperative for their long-term survival that a strategic view, rather than just a tactical, reactive or operational view, is taken of their CSR activities. Furthermore, it will help organisations to confidently predict positive intentions towards the sales of goods and services.
Originality/value
The outcome of this study has filled the CSR lacuna in the context of a developing country, as well as adding new insights into the influence and perceived value of CSR on intended consumer buying behaviour. Consumers, irrespective of their age and background, are getting wiser and cautious in purchasing products from companies which are CSR-oriented, in particular, in relation to social, legal, ethical and philanthropic perspectives.
PDF
