Moving from serotonin to serotonin-norepinephrine enhancement with increasing venlafaxine dose: clinical implications and strategies for a successful outcome in major depressive disorder

IntroductionMental health disorders, especially depressive and anxiety disorders, are associated with substantial health-related burden. While the second-generation antidepressants are widely accepted as first-line pharmacological treatment for major depressive disorder (MDD), patient response to such treatment is variable, with more than half failing to achieve complete remission, and residual symptoms are frequently present.Areas coveredHere, the pharmacodynamics of venlafaxine XR are reviewed in relation to its role as both a selective serotonin reuptake inhibitor (SSRI) and a serotonin-norepinephrine-reuptake inhibitor (SNRI), and we look at how these pharmacodynamic properties can be harnessed to guide clinical practice, asking the question 'is it possible to develop a symptom-cluster-based approach to the treatment of MDD with comorbid anxiety utilizing venlafaxine XR?.' Additionally, three illustrative clinical cases provide practical examples of the utility of venlafaxine-XR in real-world clinical practice. The place of venlafaxine XR in managing fatigue/low energy, a frequent residual symptom in MDD, is explored using pooled data from clinical trials of venlafaxine XR.Expert opinionVenlafaxine XR should be considered as a first-line treatment for MDD with or without comorbid anxiety, and there are clear pharmacodynamic signals supporting a symptom cluster-based treatment paradigm for venlafaxine XR

Effects of glucose and glutamine concentrations in human dental pulp stem cells viability. An approach for cell transplantation

PURPOSE:To evaluate microscopic behavior and viability of dental pulp stem cells under glucose and glutamine deprivation.METHODS:Human tooth tissues were minced in isolated pieces and cultured until the desired cellular proliferation for experimental phases. Cells were cultured under variations of glucose and glutamine in both serum presence and absence, and then those cells were evaluated according to number and viability by MTT assay. The confocal microscopy analyzed cytoskeleton, nucleus, and mitochondria integrity.RESULTS:A low concentration of glucose favored cellular viability and microscopic behavior; the presence of glutamine in culture medium was favorable only when associated with glucose. The cellular biological potential in culture could be preserved in serum absence if nutritional requirements are adequate.CONCLUSION:Cell microscopic behavior and viability have demonstrated better patterns on serum-free low glucose culture medium with glutamine deprivation.Federal University of São Paulo Paulista School of MedicineScience and Technology InstituteUNIFESP-EPMUniversidade Federal de São Paulo (UNIFESP) Department of SurgeryUNIFESP-EPM Surgery DepartmentUNIFESP, Paulista School of MedicineUNIFESP-EPMUNIFESP, Department of SurgeryUNIFESP, EPM Surgery DepartmentSciEL

Mesenchymal Stem Cell-Mediated Functional Tooth Regeneration in Swine

Mesenchymal stem cell-mediated tissue regeneration is a promising approach for regenerative medicine for a wide range of applications. Here we report a new population of stem cells isolated from the root apical papilla of human teeth (SCAP, stem cells from apical papilla). Using a minipig model, we transplanted both human SCAP and periodontal ligament stem cells (PDLSCs) to generate a root/periodontal complex capable of supporting a porcelain crown, resulting in normal tooth function. This work integrates a stem cell-mediated tissue regeneration strategy, engineered materials for structure, and current dental crown technologies. This hybridized tissue engineering approach led to recovery of tooth strength and appearance

Surviving crack: a qualitative study of the strategies and tactics developed by Brazilian users to deal with the risks associated with the drug

<p>Abstract</p> <p>Background</p> <p>Due to marginalization, trafficking violence, conflicts with the police and organic and social psychological problems associated with the drug, crack is one of the most devastating drugs currently in use. However, there is evidence that some users manage to stay alive and active while using crack cocaine for many years, despite the numerous adversities and risks involved with this behavior. In this context, the aim of the present study was to identify the strategies and tactics developed by crack users to deal with the risks associated with the culture of use by examining the survival strategies employed by long-term users.</p> <p>Method</p> <p>A qualitative research method was used involving semi-structured, in-depth interviews. Twenty-eight crack users fulfilling a pre-defined enrollment criterion were interviewed. This criterion was defined as the long-term use of crack (i.e., at least four years). The sample was selected using information provided by key informants and distributed across eight different supply chains. The interviews were literally transcribed and analyzed via content analysis techniques using NVivo-8 software.</p> <p>Results</p> <p>There was diversity in the sample with regard to economic and education levels. The average duration of crack use was 11.5 years. Respondents believed that the greatest risks of crack dependence were related to the drug's psychological effects (e.g., cravings and transient paranoid symptoms) and those arising from its illegality (e.g., clashes with the police and trafficking). Protection strategies focused on the control of the psychological effects, primarily through the consumption of alcohol and marijuana. To address the illegality of the drug, strategies were developed to deal with dealers and the police; these strategies were considered crucial for survival.</p> <p>Conclusions</p> <p>The strategies developed by the respondents focused on trying to protect themselves. They proved generally effective, though they involved risks of triggering additional problems (e.g., other dependencies) in the long term.</p

Reaching the Hard-to-Reach: A Probability Sampling Method for Assessing Prevalence of Driving under the Influence after Drinking in Alcohol Outlets

Drinking alcoholic beverages in places such as bars and clubs may be associated with harmful consequences such as violence and impaired driving. However, methods for obtaining probabilistic samples of drivers who drink at these places remain a challenge – since there is no a priori information on this mobile population – and must be continually improved. This paper describes the procedures adopted in the selection of a population-based sample of drivers who drank at alcohol selling outlets in Porto Alegre, Brazil, which we used to estimate the prevalence of intention to drive under the influence of alcohol. The sampling strategy comprises a stratified three-stage cluster sampling: 1) census enumeration areas (CEA) were stratified by alcohol outlets (AO) density and sampled with probability proportional to the number of AOs in each CEA; 2) combinations of outlets and shifts (COS) were stratified by prevalence of alcohol-related traffic crashes and sampled with probability proportional to their squared duration in hours; and, 3) drivers who drank at the selected COS were stratified by their intention to drive and sampled using inverse sampling. Sample weights were calibrated using a post-stratification estimator. 3,118 individuals were approached and 683 drivers interviewed, leading to an estimate that 56.3% (SE = 3,5%) of the drivers intended to drive after drinking in less than one hour after the interview. Prevalence was also estimated by sex and broad age groups. The combined use of stratification and inverse sampling enabled a good trade-off between resource and time allocation, while preserving the ability to generalize the findings. The current strategy can be viewed as a step forward in the efforts to improve surveys and estimation for hard-to-reach, mobile populations