Sympathomimetic effects of chronic methamphetamine abuse on oral health: a cross-sectional study

Background: Methamphetamine, a highly addictive sympathomimetic stimulant, is currently widely abused worldwide and has been associated with devastating effects on oral health, resulting in the term "meth mouth". However, "meth mouth" pathology is primarily based on case reports with a lack of systematic clinical evaluation. Therefore, we have conducted a systematic study to investigate (1) the pharmacological impact of methamphetamine on oral health with regard to saliva function, including the parameters saliva flow rate and total saliva production (ml/5 min) and the buffering capacity of saliva;(2) the contribution of the symptoms of bruxism and muscle trismus to potential oral health damage. Methods: We assessed the data of 100 chronic methamphetamine abusers and 100 matched-pair comparison participants. Primarily, we conducted an anamnesis with all methamphetamine abusers with regard to saliva dysfunctions, jaw clenching and pain in the temporomandibular joint. Subsequently, in the first part of the clinical enquiry, we tested the saliva flow rate and the total saliva production (ml/5 min) by using the sialometry method and the buffer capacity of saliva by determining the pH-value. In the second part of the clinical enquiry, we evaluated bruxism symptoms with respect to generalized tooth attrition, dentine exposure and visible enamel cracks and examined a potential muscle trismus by measuring the maximal opening of the mouth. Results: The majority of methamphetamine abusers reported a dry mouth (72 %) and jaw clenching (68 %). Almost half of all methamphetamine abusers experienced pain in the temporomandibular joint (47 %). With regard to the clinical findings, methamphetamine abusers showed significantly lower total saliva production (ml/5 min) (p 0.05). Conclusions: The sympathomimetic effects of chronic methamphetamine abuse may lead to dry mouth and extensive bruxism and therefore can increase the risk for caries decay, periodontal lesions and tooth wear. Furthermore, a significant decline of saliva buffer capacity in methamphetamine abusers may trigger the risk for dental erosions. Methamphetamine abusers and practitioners should be aware of these symptoms

Towards pain-free diagnosis of skin diseases through multiplexed microneedles: biomarker extraction and detection using a highly sensitive blotting method

Immunodiagnostic microneedles provide a novel way to extract protein biomarkers from the skin in a minimally invasive manner for analysis in vitro. The technology could overcome challenges in biomarker analysis specifically in solid tissue, which currently often involves invasive biopsies. This study describes the development of a multiplex immunodiagnostic device incorporating mechanisms to detect multiple antigens simultaneously, as well as internal assay controls for result validation. A novel detection method is also proposed. It enables signal detection specifically at microneedle tips and therefore may aid the construction of depth profiles of skin biomarkers. The detection method can be coupled with computerised densitometry for signal quantitation. The antigen specificity, sensitivity and functional stability of the device were assessed against a number of model biomarkers. Detection and analysis of endogenous antigens (interleukins 1α and 6) from the skin using the device was demonstrated. The results were verified using conventional enzyme-linked immunosorbent assays. The detection limit of the microneedle device, at ≤10 pg/mL, was at least comparable to conventional plate-based solid-phase enzyme immunoassays

Phenotypic Variation and Bistable Switching in Bacteria

Microbial research generally focuses on clonal populations. However, bacterial cells with identical genotypes frequently display different phenotypes under identical conditions. This microbial cell individuality is receiving increasing attention in the literature because of its impact on cellular differentiation, survival under selective conditions, and the interaction of pathogens with their hosts. It is becoming clear that stochasticity in gene expression in conjunction with the architecture of the gene network that underlies the cellular processes can generate phenotypic variation. An important regulatory mechanism is the so-called positive feedback, in which a system reinforces its own response, for instance by stimulating the production of an activator. Bistability is an interesting and relevant phenomenon, in which two distinct subpopulations of cells showing discrete levels of gene expression coexist in a single culture. In this chapter, we address techniques and approaches used to establish phenotypic variation, and relate three well-characterized examples of bistability to the molecular mechanisms that govern these processes, with a focus on positive feedback.

Development of a Three-Dimensional In Vitro Model for Longitudinal Observation of Cell Behavior: Monitoring by Magnetic Resonance Imaging and Optical Imaging

Purpose: The aim of this study is the development of a three-dimensional multicellular spheroid cell culture model for the longitudinal comparative and large-scale screening of cancer cell proliferation with noninvasive molecular imaging techniques under controlled and quantifiable conditions. Procedures: The human glioblastoma cell line Gli36ΔEGFR was genetically modified to constitutively express the fluorescence protein mCherry, and additionally labeled with iron oxide nanoparticles for high-field MRI detection. The proliferation of aggregates was longitudinally monitored with fluorescence imaging and correlated with aggregate size by light microscopy, while MRI measurements served localization in 3D space. Irradiation with γ-rays was used to detect proliferational response. Results: Cell proliferation in the stationary three-dimensonal model can be observed over days with high accuracy. A linear relationship of fluorescence intensity with cell aggregate size was found, allowing absolute quantitation of cells in a wide range of cell amounts. Glioblastoma cells showed pronounced suppression of proliferation for several days following high-dose γ-irradiation. Conclusions: Through the combination of two-dimensional optical imaging and 3D MRI, the position of individual cell aggregates and their corresponding light emission can be detected. This allows an exact quantification of cell proliferation, with a focus on very small cell amounts (below 100 cells) using high resolution noninvasive techniques as a well-controlled basis for further cell transplantation studies

Financial incentives to improve adherence to anti-psychotic maintenance medication in non-adherent patients - a cluster randomised controlled trial (FIAT)

Background Various interventions have been tested to achieve adherence to anti-psychotic maintenance medication in non-adherent patients with psychotic disorders, and there is no consistent evidence for the effectiveness of any established intervention. The effectiveness of financial incentives in improving adherence to a range of treatments has been demonstrated; no randomised controlled trial however has tested the use of financial incentives to achieve medication adherence for patients with psychotic disorders living in the community. Methods/Design In a cluster randomised controlled trial, 34 mental health teams caring for difficult to engage patients in the community will be randomly allocated to either the intervention group, where patients will be offered a financial incentive for each anti-psychotic depot medication they receive over a 12 month period, or the control group, where all patients will receive treatment as usual. We will recruit 136 patients with psychotic disorders who use these services and who have problems adhering to antipsychotic depot medication, although all conventional methods to achieve adherence have been tried. The primary outcome will be adherence levels, and secondary outcomes are global clinical improvement, number of voluntary and involuntary hospital admissions, number of attempted and completed suicides, incidents of physical violence, number of police arrests, number of days spent in work/training/education, subjective quality of life and satisfaction with medication. We will also establish the cost effectiveness of offering financial incentives. Discussion The study aims to provide new evidence on the effectiveness and cost effectiveness of offering financial incentives to patients with psychotic disorders to adhere to antipsychotic maintenance medication. If financial incentives improve adherence and lead to better health and social outcomes, they may be recommended as one option to improve the treatment of non-adherent patients with psychotic disorders. Trial Registration Current controlled trials ISRCTN77769281

Skin parasite landscape determines host infectiousness in visceral leishmaniasis

Increasing evidence suggests that the infectiousness of patients for the sand fly vector of visceral leishmaniasis is linked to parasites found in the skin. Using a murine model that supports extensive skin infection with Leishmania donovani, spatial analyses at macro-(quantitative PCR) and micro-(confocal microscopy) scales indicate that parasite distribution is markedly skewed. Mathematical models accounting for this heterogeneity demonstrate that while a patchy distribution reduces the expected number of sand flies acquiring parasites, it increases the infection load for sand flies feeding on a patch, increasing their potential for onward transmission. Models representing patchiness at both macro- and micro-scales provide the best fit with experimental sand fly feeding data, pointing to the importance of the skin parasite landscape as a predictor of host infectiousness. Our analysis highlights the skin as a critical site to consider when assessing treatment efficacy, transmission competence and the impact of visceral leishmaniasis elimination campaigns.Parasitemia has been considered the main determinant of visceral leishmaniasis transmission. By combining imaging, qPCR and experimental xenodiagnoses with mathematical models, Doehl et al. argue that the patchy landscape of parasites in the skin is necessary to explain infectiousness

Health and Oral Health Care Needs and Health Care-Seeking Behavior Among Homeless Injection Drug Users in San Francisco

Few existing studies have examined health and oral health needs and treatment-seeking behavior among the homeless and injection drug users (IDUs). This paper describes the prevalence and correlates of health and oral health care needs and treatment-seeking behaviors in homeless IDUs recruited in San Francisco, California, from 2003 to 2005 (N = 340). We examined sociodemographic characteristics, drug use patterns, HIV status via oral fluid testing, physical health using the Short Form 12 Physical Component Score, self-reported needs for physical and oral health care, and the self-reported frequency of seeking medical and oral health care. The sample had a lower health status as compared to the general population and reported a frequent need for physical and oral health care. In bivariate analysis, being in methadone treatment was associated with care-seeking behavior. In addition, being enrolled in Medi-Cal, California’s state Medicaid program, was associated with greater odds of seeking physical and oral health care. Methamphetamine use was not associated with higher odds of needing oral health care as compared to people who reported using other illicit drugs. Homeless IDUs in San Francisco have a large burden of unmet health and oral health needs. Recent cuts in Medi-Cal’s adult dental coverage may result in a greater burden of oral health care which will need to be provided by emergency departments and neighborhood dental clinics

Heterogeneous Response to a Quorum-Sensing Signal in the Luminescence of Individual Vibrio fischeri

The marine bacterium Vibrio fischeri regulates its bioluminescence through a quorum sensing mechanism: the bacterium releases diffusible small molecules (autoinducers) that accumulate in the environment as the population density increases. This accumulation of autoinducer (AI) eventually activates transcriptional regulators for bioluminescence as well as host colonization behaviors. Although V.fischeri quorum sensing has been extensively characterized in bulk populations, far less is known about how it performs at the level of the individual cell, where biochemical noise is likely to limit the precision of luminescence regulation. We have measured the time-dependence and AI-dependence of light production by individual V.fischeri cells that are immobilized in a perfusion chamber and supplied with a defined concentration of exogenous AI. We use low-light level microscopy to record and quantify the photon emission from the cells over periods of several hours as they respond to the introduction of AI. We observe an extremely heterogeneous response to the AI signal. Individual cells differ widely in the onset time for their luminescence and in their resulting brightness, even in the presence of high AI concentrations that saturate the light output from a bulk population. The observed heterogeneity shows that although a given concentration of quorum signal may determine the average light output from a population of cells, it provides far weaker control over the luminescence output of each individual cell

Herpesviruses carrying a Brainbow cassette reveal replication and expression of limited numbers of incoming genomes

Whether all the infectious herpesvirus particles entering a cell are able to replicate and/or express their genomes is not known. Here, we developed a general method to determine the number of viral genomes expressed in an infected cell. We constructed and analysed fluorophore expression from a recombinant pseudorabies virus (PRV263) carrying a Brainbow cassette (Cre-conditional expression of different fluorophores). Using three isogenic strains derived from PRV263, each expressing a single fluorophore, we analysed the colour composition of cells infected with these three viruses at different multiplicities. We estimate that fewer than seven incoming genomes are expressed per cell. In addition, those templates that are expressed are the genomes selected for replication and packaging into virions. This finite limit on the number of viral genomes that can be expressed is an intrinsic property of the infected cell and may be influenced by viral and cellular factors

The effect of dopamine agonists on adaptive and aberrant salience in Parkinson's disease

Clinical evidence suggests that after initiation of dopaminergic medications some patients with Parkinson's disease (PD) develop psychotic symptoms, such as hallucinations and delusions. Here, we tested the hypothesis that the neurocognitive basis of this phenomenon can be defined as the formation of arbitrary and illusory associations between conditioned stimuli and reward signals, called aberrant salience. Young, never-medicated PD patients and matched controls were assessed on a speeded reaction time task in which the probe stimulus was preceded by conditioned stimuli that could signal monetary reward by color or shape. The patients and controls were re-evaluated after 12 weeks during which the patients received a dopamine agonist (pramipexole or ropinirole). Results indicated that dopamine agonists increased both adaptive and aberrant salience in PD patients, that is, formation of real and illusory associations between conditioned stimuli and reward, respectively. This effect was present when associations were assessed by means of faster responding after conditioned stimuli signaling reward (implicit salience) and overt rating of stimulus-reward links (explicit salience). However, unusual feelings and experiences, which are subclinical manifestations of psychotic-like symptoms, were specifically related to irrelevant and illusory stimulus-reward associations (aberrant salience) in PD patients receiving dopamine agonists. The learning of relevant and real stimulus-reward associations (adaptive salience) was not related to unusual experiences. These results suggest that dopamine agonists may increase psychotic-like experiences in young patients with PD, possibly by facilitating dopaminergic transmission in the ventral striatum, which results in aberrant associations between conditioned stimuli and reward