Crucial role of α4 and α6 nicotinic acetylcholine receptor subunits from ventral tegmental area in systemic nicotine self-administration

The identification of the molecular mechanisms involved in nicotine addiction and its cognitive consequences is a worldwide priority for public health. Novel in vivo paradigms were developed to match this aim. Although the beta2 subunit of the neuronal nicotinic acetylcholine receptor (nAChR) has been shown to play a crucial role in mediating the reinforcement properties of nicotine, little is known about the contribution of the different alpha subunit partners of beta2 (i.e., alpha4 and alpha6), the homo-pentameric alpha7, and the brain areas other than the ventral tegmental area (VTA) involved in nicotine reinforcement. In this study, nicotine (8.7-52.6 microg free base/kg/inf) self-administration was investigated with drug-naive mice deleted (KO) for the beta2, alpha4, alpha6 and alpha7 subunit genes, their wild-type (WT) controls, and KO mice in which the corresponding nAChR subunit was selectively re-expressed using a lentiviral vector (VEC mice). We show that WT mice, beta2-VEC mice with the beta2 subunit re-expressed exclusively in the VTA, alpha4-VEC mice with selective alpha4 re-expression in the VTA, alpha6-VEC mice with selective alpha6 re-expression in the VTA, and alpha7-KO mice promptly self-administer nicotine intravenously, whereas beta2-KO, beta2-VEC in the substantia nigra, alpha4-KO and alpha6-KO mice do not respond to nicotine. We thus define the necessary and sufficient role of alpha4beta2- and alpha6beta2-subunit containing nicotinic receptors (alpha4beta2*- and alpha6beta2*-nAChRs), but not alpha7*-nAChRs, present in cell bodies of the VTA, and their axons, for systemic nicotine reinforcement in drug-naive mic

Theoretical Determination of Temperature Field in Orthogonal Machining

In this work, mathematical models were developed to simulate the thermal behaviour of a cutting tool insert in three-dimensional dry machining. Models to determine the temperature rise at the shear plane and tool insert in orthogonal cutting were developed, simulated and validated. The effects of various machining parameters/variables such as specific heat of material of 4400J/kg, Depth of cut (t) of 0.0003m, Density of 7870kg/m3, Width of cut (b) of 0.005m, Chip thickness ratio (rt) of 0.42, Tool rake angle of 100, Cutting Velocity (V) of 35m/min and Shear force (Fs) of 1257.6N on temperature rise were well analyzed

Videovoice diaries to understand the perspectives of community health volunteers in Ethiopia: insights from collaborative qualitative research

Background: Audio-visual diary to collect data on daily routines of study participants is relatively new in health systems research. The concept uses participatory research techniques to elicit participants' views, priorities and empower them to take action. Methods: We discuss a collaborative qualitative study conducted by university researchers, rural communities and health managers (Southwest Ethiopia). We used Videovoice to understand the role of community health volunteers as mediators of accessible and responsive Primary Health Care in Ethiopia. Footage is obtained from 30 Health Development Army leaders in 3 diverse districts, over 3–4 months. Following community engagement and training, participants received an encrypted phone with recording capability. They are supported by researchers through regular contacts, to establish trust, support, and reduce social desirability. A co-production workshop with participants and researchers to interpret the findings will be held. Results: Employing Videovoice diaries demonstrates that collaborations involving academic researchers, community members and volunteers (as lay researchers) and managers have considerable benefits as well as challenges. Videovoice shifts power to the participants: they determine what to capture, what is important and how to convey their views and activities. Data is enriched by participant-generated insights into the reasons behind their decisions. Intensive engagement, effective communication and trust are essential in understanding constraints and preferences of their role, and interpreting findings. A multi-disciplinary research team will enhance the analytical process. Discussion: Videovoice can be a useful tool in enabling lay researchers to describe their daily life, better understand their needs, and identify mechanisms for change. The approach can strengthen the immediacy of the research, capturing perceptions within context. Co-production will involve a significant shift in power and emergence of new directions

Readiness of primary health care facilities in Jimma zone to provide diabetic services for diabetic clients, Jimma zone, southwest Ethiopia, March 2013

Published date: Oct 12, 2016Background: Diabetes is one of the commonest non-communicable diseases of the 21st century. Global burden of diabetes in 2010 was estimated at 285 million and projected to increase to 438 million by the year 2030, if no interventions are put in place. The primary health care facilities are the first level of contact for such rising cases of diabetes, despite of this fact there is no study done on the capabilities of primary health care facilities to accommodate diabetic services. Hence, the objective of this study is to assess the readiness of selected primary public hospitals and health centers to accommodate diabetic care in Jimma zone south west Ethiopia. Methods: Health facility based cross-sectional study design using quantitative and qualitative method of data collection was conducted from Feb 1-March 1, 2013. After checking the completeness, and coding of questionnaires, the quantitative data were entered into computer software and analyzed using SPSS version 20.0. Results: All of the facilities have at least some of the drugs and medical supplies and other resources required for the diagnosis and management of diabetes never the less there was no specific plan to deal with diabetic management at health facilities. Majority of patients were first diagnosed in other health facilities and referred to the current health institutions for follow up and there is no routine screening for diabetics in adult outpatient department in some health facilities. Conclusion and recommendation: Required drugs and medical supplies are not regularly fulfilled, health facilities have no plan for diabetic management, and health workers did not get training on management of diabetics. No routine screening at adult patients at outpatient departments. Hence the Woreda and the zone have to work on the capacity of the health workers and health facilities to handle diabetic care at health center level.Fikru Tafese, Elias Teferi, Beyene Wondafirash, Sintayehu Fekadu, Garumma Tolu and Gugsa Nemarr

Tuberculosis, Human Immunodeficiency Virus, and the Association With Transient Hyperglycemia in Periurban South Africa

Abstract Background Diabetes mellitus (DM) increases tuberculosis (TB) risk. We assessed the prevalence of hyperglycemia (DM and impaired glucose regulation [IGR]) in persons with TB and the association between hyperglycemia and TB at enrollment and 3 months after TB treatment in the context of human immunodeficiency virus (HIV) infection. Methods Adults presenting at a Cape Town TB clinic were enrolled. TB cases were defined by South African guidelines, while non-TB participants were those who presented with respiratory symptoms, negative TB tests, and resolution of symptoms 3 months later without TB treatment. HIV status was ascertained through medical records or HIV testing. All participants were screened for DM using glycated hemoglobin and fasting plasma glucose at TB treatment and after 3 months. The association between TB and DM was assessed. Results Overall DM prevalence was 11.9% (95% confidence interval [CI], 9.1%–15.4%) at enrollment and 9.3% (95% CI, 6.4%–13%) at follow-up; IGR prevalence was 46.9% (95% CI, 42.2%–51.8%) and 21.5% (95% CI, 16.9%–26.3%) at enrollment and follow-up. TB/DM association was significant at enrollment (odds ratio [OR], 2.41 [95% CI, 1.3–4.3]) and follow-up (OR, 3.3 [95% CI, 1.5–7.3]), whereas TB/IGR association was only positive at enrollment (OR, 2.3 [95% CI, 1.6–3.3]). The TB/DM association was significant at enrollment in both new and preexisting DM, but only persisted at follow-up in preexisting DM in patients with HIV-1 infection. Conclusions Our study demonstrated high prevalence of transient hyperglycemia and a significant TB/DM and TB/IGR association at enrollment in newly diagnosed DM, but persistent hyperglycemia and TB/DM association in patients with HIV-1 infection and preexisting DM, despite TB therapy. This work was supported by the Wellcome Trust (grant numbers 084323, 104873, and 203135), a Carnegie Corporation Postdoctoral Fellowship, and a Harry Crossley Senior Clinical Fellowship. R. J. W. is supported by the Francis Crick Institute, which receives funding from Cancer Research UK (grant number FC001010218), Research Councils UK (grant number FC0010218), and the Wellcome Trust (grant number FC0010218). He also receives support from the National Institutes of Health (NIH) (grant number U1 AI115940), NIH (grant number WILK116PTB), and European and Developing Countries Clinical Trials Partnership (grant number SRIA 2015–1065). M. K. is supported by the South African Centre for Epidemiological Modelling and Analysis, the International Epidemiology Databases to Evaluate AIDS, and the NIH (grant number U01AI069924)

Structure-based design of functionalized 2-substituted and 1,2- disubstituted benzimidazole derivatives and their in vitro antibacterial efficacy

The aim of this present study was to synthesize 2-substituted and 1,2-disubstituted benzimidazole derivatives to investigate their antibacterial diversity for possible future drug design. The structurebased design of precursors 2-(1H-benzimidazol-2-yl)aniline 1, 2-(3,5-dinitro phenyl)-1Hbenzimidazole 3 and 2-benzyl-1H-benzimidazole 5 were achieved by the condensation reaction of ophenylenediamine with anthranilic acid, 3,5-dinitrophenylbenzoic acid, and phenylacetic acid, respectively. The precursors 1, 3 and 5, upon reaction with six different electrophile-releasing agents, furnished the corresponding 2-substituted benzimidazole, 2a-f and 1,2-disubstituted benzimidazole derivatives 4a-f and 6a-f, respectively. The structural identity of the targeted compounds was authenticated by elemental analytical data and spectral information from FT-IR, UV, 1H, and 13C NMR. The outcome of the findings from the in vitro screening unveiled 2-benzyl-1-(phenylsulfonyl)-1H-benzimidazole 6b as the most active derivative with lowest MIC value of 15.63 mg/m

Chronic diseases and multi-morbidity - a conceptual modification to the WHO ICCC model for countries in health transition

Background: The burden of non-communicable diseases is rising, particularly in low and middle-income countries undergoing rapid epidemiological transition. In sub-Saharan Africa, this is occurring against a background of infectious chronic disease epidemics, particularly HIV and tuberculosis. Consequently, multi-morbidity, the co-existence of more than one chronic condition in one person, is increasing; in particular multimorbidity due to comorbid non-communicable and infectious chronic diseases (CNCICD). Such complex multimorbidity is a major challenge to existing models of healthcare delivery and there is a need to ensure integrated care across disease pathways and across primary and secondary care. Discussion: The Innovative Care for Chronic Conditions (ICCC) Framework developed by the World Health Organization provides a health systems roadmap to meet the increasing needs of chronic disease care. This framework incorporates community, patient, healthcare and policy environment perspectives, and forms the cornerstone of South Africa’s primary health care re-engineering and strategic plan for chronic disease management integration. However, it does not significantly incorporate complexity associated with multimorbidity and CNCICD. Using South Africa as a case study for a country in transition, we identify gaps in the ICCC framework at the micro-, meso-, and macro-levels. We apply the lens of CNCICD and propose modification of the ICCC and the South African Integrated Chronic Disease Management plan. Our framework incorporates the increased complexity of treating CNCICD patients, and highlights the importance of biomedicine (biological interaction). We highlight the patient perspective using a patient experience model that proposes that treatment adherence, healthcare utilization, and health outcomes are influenced by the relationship between the workload that is delegated to patients by healthcare providers, and patients’ capacity to meet the demands of this workload. We link these issues to provider perspectives that interact with healthcare delivery and utilization. Summary: Our proposed modification to the ICCC Framework makes clear that healthcare systems must work to make sense of the complex collision between biological phenomena, clinical interpretation, beliefs and behaviours that follow from these. We emphasize the integration of these issues with the socio-economic environment to address issues of complexity, access and equity in the integrated management of chronic diseases previously considered in isolation