Come back when you’re infected: pharmacy access to sterile syringes in an Arizona Secret Shopper Study, 2023

Background: Pharmacies are critical healthcare partners in community efforts to eliminate bloodborne illnesses. Pharmacy sale of sterile syringes is central to this effort. Methods: A mixed methods “secret shopper” syringe purchase study was conducted in the fall of 2022 with 38 community pharmacies in Maricopa and Pima Counties, Arizona. Pharmacies were geomapped to within 2 miles of areas identified as having a potentially high volume of illicit drug commerce. Daytime venue sampling was used whereby separate investigators with lived/living drug use experience attempted to purchase syringes without a prescription. Investigator response when prompted for purchase rationale was “to protect myself from HIV and hepatitis C.” A 24-item instrument measured sales outcome, pharmacy staff interaction (hostile/neutral/friendly), and the buyer’s subjective experience. Results: Only 24.6% (n = 28) of 114 purchase attempts across the 38 pharmacies resulted in syringe sale. Less than one quarter (21.1%) of pharmacies always sold, while 44.7% never sold. Independent and food store pharmacies tended not to sell syringes. There emerged distinct pharmacy staff interactions characterized by body language, customer query, normalization or othering response, response to purchase request and closure. Pharmacy discretion and pharmacy policy not to sell syringes without a prescription limited sterile syringe access. Investigators reported frequent and adverse emotional impact due to pharmacy staff negative and stigmatizing interactions. Conclusions: Pharmacies miss opportunities to advance efforts to eliminate bloodborne infections by stringent no-sale policy and discretion about syringe sale. State regulatory policy facilitating pharmacy syringe sales, limiting pharmacist discretion for syringe sales, and targeting pharmacy-staff level education may help advance the achievement of public health goals to eliminate bloodborne infections in Arizona

An exploratory investigation of brain collateral circulation plasticity after cerebral ischemia in two experimental C57BL/6 mouse models

Brain collateral circulation is an essential compensatory mechanism in response to acute brain ischemia. To study the temporal evolution of brain macro and microcollateral recruitment and their reciprocal interactions in response to different ischemic conditions, we applied a combination of complementary techniques (T2-weighted magnetic resonance imaging [MRI], time of flight [TOF] angiography [MRA], cerebral blood flow [CBF] imaging and histology) in two different mouse models. Hypoperfusion was either induced by permanent bilateral common carotid artery stenosis (BCCAS) or 60-min transient unilateral middle cerebral artery occlusion (MCAO). In both models, collateralization is a very dynamic phenomenon with a global effect affecting both hemispheres. Patency of ipsilateral posterior communicating artery (PcomA) represents the main variable survival mechanism and the main determinant of stroke lesion volume and recovery in MCAO, whereas the promptness of external carotid artery retrograde flow recruitment together with PcomA patency, critically influence survival, brain ischemic lesion volume and retinopathy in BCCAS mice. Finally, different ischemic gradients shape microcollateral density and size

External Control of the GAL Network in S. cerevisiae: A View from Control Theory

While there is a vast literature on the control systems that cells utilize to regulate their own state, there is little published work on the formal application of control theory to the external regulation of cellular functions. This paper chooses the GAL network in S. cerevisiae as a well understood benchmark example to demonstrate how control theory can be employed to regulate intracellular mRNA levels via extracellular galactose. Based on a mathematical model reduced from the GAL network, we have demonstrated that a galactose dose necessary to drive and maintain the desired GAL genes' mRNA levels can be calculated in an analytic form. And thus, a proportional feedback control can be designed to precisely regulate the level of mRNA. The benefits of the proposed feedback control are extensively investigated in terms of stability and parameter sensitivity. This paper demonstrates that feedback control can both significantly accelerate the process to precisely regulate mRNA levels and enhance the robustness of the overall cellular control system

Caspase-8 activity has an essential role in CD95/Fas-mediated MAPK activation

Stimulation of CD95/Fas/APO-1 results in the induction of both apoptotic and non-apoptotic signaling pathways. The processes regulating these two opposing pathways have not been thoroughly elucidated to date. In this study, using quantitative immunoblots, imaging, and mathematical modeling, we addressed the dynamics of the DED proteins of the death-inducing signaling complex (DISC), procaspase-8, and cellular FLICE inhibitory proteins (c-FLIPs) to the onset of CD95-mediated ERK1/2 and p38 mitogen-activated protein kinase (MAPK) activation. We found that CD95 DISC-induced caspase-8 activity is important for the initiation of ERK1/2 and p38 MAPK activation. The long c-FLIP isoform, c-FLIPL, and the short c-FLIP isoform, c-FLIPR, inhibited MAPK induction by blocking caspase-8 processing at the DISC. Furthermore, we built a mathematical model describing CD95 DISC-mediated MAPK activation and apoptosis. The model quantitatively defined the dynamics of DED proteins, procaspase-8, and c-FLIP, which lead to caspase-8 activation and induction of apoptotic and non-apoptotic signaling pathways. In conclusion, the combination of biochemical analysis with mathematical modeling provides evidence for an important role of caspase-8 in CD95-mediated activation of MAPKs, while c-FLIP exerts a regulatory function in this process

Modulation of the CD95-Induced Apoptosis: The Role of CD95 N-Glycosylation

Protein modifications of death receptor pathways play a central role in the regulation of apoptosis. It has been demonstrated that O-glycosylation of TRAIL-receptor (R) is essential for sensitivity and resistance towards TRAIL-mediated apoptosis. In this study we ask whether and how glycosylation of CD95 (Fas/APO-1), another death receptor, influences DISC formation and procaspase-8 activation at the CD95 DISC and thereby the onset of apoptosis. We concentrated on N-glycostructure since O-glycosylation of CD95 was not found. We applied different approaches to analyze the role of CD95 N-glycosylation on the signal transduction: in silico modeling of CD95 DISC, generation of CD95 glycosylation mutants (at N136 and N118), modulation of N-glycosylation by deoxymannojirimycin (DMM) and sialidase from Vibrio cholerae (VCN). We demonstrate that N-deglycosylation of CD95 does not block DISC formation and results only in the reduction of the procaspase-8 activation at the DISC. These findings are important for the better understanding of CD95 apoptosis regulation and reveal differences between apoptotic signaling pathways of the TRAIL and CD95 systems

Normative and self-perceived orthodontic treatment need of a Peruvian university population

BACKGROUND: Previous studies on orthodontic treatment need in young adults have shown that up to 50% had malocclusions that needed orthodontic treatment. The aims of this study were to assess the normative and self-perceived need for orthodontic treatment using the Index of Orthodontic Treatment Need (IOTN) and to determine if the treatment need levels were influenced by sex, age and socio-economic status (SES) in a sample of Peruvian young adults. METHODS: 281 first-year students (157 male and 124 female students) with a mean age of 18.1 +/- 1.6 years were randomly selected and evaluated through the Dental Health Component (DHC) and Aesthetic Component (AC) of the IOTN. Structured interview and clinical examination were used to assess the students. Descriptive statistics and Chi-square tests were used for data analysis with statistical significance set at P < 0.05. RESULTS: An intra-examiner reliability of 0.89 was obtained (weighted Kappa). The percentage of students according to SES was 51.2%, 40.6% and 8.2% corresponding to low, medium and high SES respectively. The percentage of students with DHC grades 4–5 was 29.9% whereas the percentage of students with AC grades 8–10 was 1.8%. There were no significant differences in the distribution of normative and self-perceived orthodontic treatment need based on sex, age and SES comparisons. CONCLUSION: Normative orthodontic treatment need was not matched by a similar level of self-perceived treatment need in these young adults. Sex, age and SES were non-significant factors associated with levels of treatment need

Progress in Diamond Detector Development

Detectors based on Chemical Vapor Deposition (CVD) diamond have been used successfully in Luminosity and Beam Condition Monitors (BCM) in the highest radiation areas of the LHC. Future experiments at CERN will accumulate an order of magnitude larger fluence. As a result, an enormous effort is underway to identify detector materials that can operate under fluences of 1 · 1016 n cm−2 and 1 · 1017 n cm−2. Diamond is one candidate due to its large displacement energy that enhances its radiation tolerance. Over the last 30 years the RD42 collaboration has constructed diamond detectors in CVD diamond with a planar geometry and with a 3D geometry to extend the material's radiation tolerance. The 3D cells in these detectors have a size of 50 µm×50 µm with columns of 2.6 µm in diameter and 100 µm×150 µm with columns of 4.6 µm in diameter. Here we present the latest beam test results from planar and 3D diamond pixel detectors