Aspiration Before Tissue Filler—An Exercise in Futility and Unsafe Practice

Background: Aesthetic physicians rely on certain anecdotal beliefs regarding the safe practice of filler injections. These include a presumed safety advantage of bolus injection after a negative aspiration. Objectives: The authors sought to review and summarize the published literature on inadvertent intravascular injection of hyaluronic acid and to investigate whether the technique of aspiration confers any safety to the practitioner and the patient. Methods: Pertinent literature was analyzed and the current understanding of the safety of negative and positive aspiration outlined. Results: The available studies demonstrate that aspiration cannot be relied on and should not be employed as a safety measure. It is safer to adopt injection techniques that avoid injecting an intravascular volume with embolic potential than utilize an unreliable test to permit a risky injection. Conclusions: To prevent intravascular injection, understanding "injection anatomy"and injection plane and techniques such as slow, low-pressure injection are important safety measures. Assurance of safety when delivering a bolus after negative aspiration does not appear to be borne out by the available literature. If there is any doubt about the sensitivity or reliability of a negative aspiration, there is no role for its utilization. Achieving a positive aspiration would just defer the risk to the next injection location where a negative aspiration would then be relied on

Interaction of amisulpride with GLUT1 at the blood-brain barrier. Relevance to Alzheimer’s disease

Blood-brain barrier (BBB) dysfunction may be involved in the increased sensitivity of Alzheimer's disease (AD) patients to antipsychotics, including amisulpride. Studies indicate that antipsychotics interact with facilitated glucose transporters (GLUT), including GLUT1, and that GLUT1 BBB expression decreases in AD. We tested the hypotheses that amisulpride (charge: +1) interacts with GLUT1, and that BBB transport of amisulpride is compromised in AD. GLUT1 substrates, GLUT1 inhibitors and GLUT-interacting antipsychotics were identified by literature review and their physicochemical characteristics summarised. Interactions between amisulpride and GLUT1 were studied using in silico approaches and the human cerebral endothelial cell line, hCMEC/D3. Brain distribution of [3H]amisulpride was determined using in situ perfusion in wild type (WT) and 5xFamilial AD (5xFAD) mice. With transmission electron microscopy (TEM) we investigated brain capillary degeneration in WT mice, 5xFAD mice and human samples. Western blots determined BBB transporter expression in mouse and human. Literature review revealed that, although D-glucose has no charge, charged molecules can interact with GLUT1. GLUT1 substrates are smaller (184.95±6.45g/mol) than inhibitors (325.50±14.40g/mol) and GLUT-interacting antipsychotics (369.38±16.04). Molecular docking showed beta-D-glucose (free energy binding: -15.39kcal/mol) and amisulpride (-29.04kcal/mol) interact with GLUT1. Amisulpride did not affect [14C]D-glucose hCMEC/D3 accumulation. [3H]amisulpride uptake into the brain (except supernatant) of 5xFAD mice compared to WT remained unchanged. TEM revealed brain capillary degeneration in human AD. There was no difference in GLUT1 or P-glycoprotein BBB expression between WT and 5xFAD mice. In contrast, caudate P-glycoprotein, but not GLUT1, expression was decreased in human AD capillaries versus controls. This study provides new details about the BBB transport of amisulpride, evidence that amisulpride interacts with GLUT1 and that BBB transporter expression is altered in AD. This suggests that antipsychotics could potentially exacerbate the cerebral hypometabolism in AD. Further research into the mechanism of amisulpride transport by GLUT1 is important for improving antipsychotics safety

Predominance of Rotavirus P[4]G2 in a Vaccinated Population, Brazil

We identified 21 rotaviruses in 129 patients with diarrhea in a Brazilian city with high rotavirus vaccine coverage. All rotaviruses were genotype P[4]G2 with 1 mixed infection with P[NT]G9. Although virus predominance could have occurred randomly, the vaccine may be less protective against P[4]G2. Prospective surveillance is urgently needed

High Cysteinyl Leukotriene Receptor 1 Expression Correlates with Poor Survival of Uveal Melanoma Patients and Cognate Antagonist Drugs Modulate the Growth, Cancer Secretome, and Metabolism of Uveal Melanoma Cells

Simple Summary This research investigates the disease relevance and therapeutic potential of cysteinyl leukotriene receptors in uveal melanoma (UM), a rare eye cancer that often spreads to the liver. Unfortunately, there are no therapies available to stop the spread of UM and patients are often faced with an extremely poor prognosis. We assess whether the cysteinyl leukotriene receptors (CysLT(1) and CysLT(2)) are relevant to the progression of UM. Using UM patient samples, we identified that increased levels of CysLT(1) in tumours is associated with reduced patient survival. Using UM cell lines and zebrafish models, we found that drugs targeting CysLT(1), but not CysLT(2), can alter hallmarks of cancer including cell growth, proliferation, and metabolism. This study is the first to examine the relationship of the CysLT receptors with clinical features of UM. Our data strengthen the importance of CysLT signalling in UM and suggest that antagonism of CysLT(1) may be of therapeutic interest in the disease. Metastatic uveal melanoma (UM) is a rare, but often lethal, form of ocular cancer arising from melanocytes within the uveal tract. UM has a high propensity to spread hematogenously to the liver, with up to 50% of patients developing liver metastases. Unfortunately, once liver metastasis occurs, patient prognosis is extremely poor with as few as 8% of patients surviving beyond two years. There are no standard-of-care therapies available for the treatment of metastatic UM, hence it is a clinical area of urgent unmet need. Here, the clinical relevance and therapeutic potential of cysteinyl leukotriene receptors (CysLT(1) and CysLT(2)) in UM was evaluated. High expression of CYSLTR1 or CYSLTR2 transcripts is significantly associated with poor disease-free survival and poor overall survival in UM patients. Digital pathology analysis identified that high expression of CysLT(1) in primary UM is associated with reduced disease-specific survival (p = 0.012; HR 2.76; 95% CI 1.21-6.3) and overall survival (p = 0.011; HR 1.46; 95% CI 0.67-3.17). High CysLT(1) expression shows a statistically significant (p = 0.041) correlation with ciliary body involvement, a poor prognostic indicator in UM. Small molecule drugs targeting CysLT(1) were vastly superior at exerting anti-cancer phenotypes in UM cell lines and zebrafish xenografts than drugs targeting CysLT(2). Quininib, a selective CysLT(1) antagonist(,) significantly inhibits survival (p < 0.0001), long-term proliferation (p < 0.0001), and oxidative phosphorylation (p < 0.001), but not glycolysis, in primary and metastatic UM cell lines. Quininib exerts opposing effects on the secretion of inflammatory markers in primary versus metastatic UM cell lines. Quininib significantly downregulated IL-2 and IL-6 in Mel285 cells (p < 0.05) but significantly upregulated IL-10, IL-1 beta, IL-2 (p < 0.0001), IL-13, IL-8 (p < 0.001), IL-12p70 and IL-6 (p < 0.05) in OMM2.5 cells. Finally, quininib significantly inhibits tumour growth in orthotopic zebrafish xenograft models of UM. These preclinical data suggest that antagonism of CysLT(1), but not CysLT(2), may be of therapeutic interest in the treatment of UM

A practical Java tool for small-molecule compound appraisal

The increased use of small-molecule compound screening by new users from a variety of different academic backgrounds calls for adequate software to administer, appraise, analyse and exchange information obtained from screening experiments. While software and spreadsheet solutions exist, there is a need for software that can be easily deployed and is convenient to use.The Java application cApp addresses this need and aids in the handling and storage of information on small-molecule compounds. The software is intended for the appraisal of compounds with respect to their physico-chemical properties, analysis in relation to adherence to likeness rules as well as recognition of pan-assay interference components and cross-linking with identical entries in the PubChem Compound Database. Results are displayed in a tabular form in a graphical interface, but can also be written in an HTML or PDF format. The output of data in ASCII format allows for further processing of data using other suitable programs. Other features include similarity searches against user-provided compound libraries and the PubChem Compound Database, as well as compound clustering based on a MaxMin algorithm.cApp is a personal database solution for small-molecule compounds which can handle all major chemical formats. Being a standalone software, it has no other dependency than the Java virtual machine and is thus conveniently deployed. It streamlines the analysis of molecules with respect to physico-chemical properties and drug discovery criteria; cApp is distributed under the GNU Affero General Public License version 3 and available from http://www.structuralchemistry.org/pcsb/. To download cApp, users will be asked for their name, institution and email address. A detailed manual can also be downloaded from this site, and online tutorials are available at http://www.structuralchemistry.org/pcsb/capp.php

Provision of mental health services in resource-poor settings: a randomised trial comparing counselling with routine medical treatment in North Afghanistan (Mazar-e-Sharif)

<p>Abstract</p> <p>Background</p> <p>Psychosocial stress caused by war, ongoing conflict, lack of security, and restricted access to resources promotes mental suffering and diseases in many resource-poor countries. In an exemplary setting, the present study compares the efficacy of psychosocial counselling with routine pharmacological treatment in a randomised trial in Mazar-e-Sharif (Afghanistan).</p> <p>Methods</p> <p>Help seeking Afghan women (N = 61), who were diagnosed with mental health symptoms by local physicians either received routine medical treatment<b/>(treatment as usual) or psychosocial counselling (5-8 sessions) following a specifically developed manualised treatment protocol. Primary outcome measures were symptoms of depression and anxiety assessed before treatment and at follow-up using the Hopkins Symptom Checklist and the Mini-International Neuropsychiatric Interview. Secondary outcome measures were psychosocial stressors and coping mechanisms.</p> <p>Results</p> <p>At 3-month follow-up, psychosocial counselling patients showed high improvements with respect to the severity of symptoms of depression and anxiety. In addition, they reported a reduction of psychosocial stressors and showed an enhancement of coping strategies. At the same time, the severity of symptoms, the quantity of psychosocial stressors and coping mechanisms did not improve in patients receiving routine medical treatment.</p> <p>Conclusion</p> <p>These results indicate that psychosocial counselling can be an effective treatment for mental illnesses even for those living in ongoing unsafe environments.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01155687">NCT01155687</a></p

Successful awake proning is associated with improved clinical outcomes in patients with COVID-19: single-centre high-dependency unit experience

The SARS-CoV-2 can lead to severe illness with COVID-19. Outcomes of patients requiring mechanical ventilation are poor. Awake proning in COVID-19 improves oxygenation, but on data clinical outcomes is limited. This single-centre retrospective study aimed to assess whether successful awake proning of patients with COVID-19, requiring respiratory support (continuous positive airways pressure (CPAP) or high-flow nasal oxygen (HFNO)) on a respiratory high-dependency unit (HDU), is associated with improved outcomes. HDU care included awake proning by respiratory physiotherapists. Of 565 patients admitted with COVID-19, 71 (12.6%) were managed on the respiratory HDU, with 48 of these (67.6%) requiring respiratory support. Patients managed with CPAP alone 22/48 (45.8%) were significantly less likely to die than patients who required transfer onto HFNO 26/48 (54.2%): CPAP mortality 36.4%; HFNO mortality 69.2%, (p=0.023); however, multivariate analysis demonstrated that increasing age and the inability to awake prone were the only independent predictors of COVID-19 mortality. The mortality of patients with COVID-19 requiring respiratory support is considerable. Data from our cohort managed on HDU show that CPAP and awake proning are possible in a selected population of COVID-19, and may be useful. Further prospective studies are required

Quantifying long-term health and economic outcomes for survivors of group B Streptococcus invasive disease in infancy: protocol of a multi-country study in Argentina, India, Kenya, Mozambique and South Africa.

Sepsis and meningitis due to invasive group B Streptococcus (iGBS) disease during early infancy is a leading cause of child mortality. Recent systematic estimates of the worldwide burden of GBS suggested that there are 319,000 cases of infant iGBS disease each year, and an estimated 147,000 stillbirths and young-infant deaths, with the highest burden occurring in Sub-Saharan Africa.  The following priority data gaps were highlighted: (1) long-term outcome data after infant iGBS, including mild disability, to calculate quality-adjusted life years (QALYs) or disability-adjusted life years (DALYs) and (2) economic burden for iGBS survivors and their families. Geographic data gaps were also noted with few studies from low- and middle- income countries (LMIC), where the GBS burden is estimated to be the highest. In this paper we present the protocol for a multi-country matched cohort study designed to estimate the risk of long-term neurodevelopmental impairment (NDI), socioemotional behaviors, and economic outcomes for children who survive invasive GBS disease in Argentina, India, Kenya, Mozambique, and South Africa. Children will be identified from health demographic surveillance systems, hospital records, and among participants of previous epidemiological studies. The children will be aged between 18 months to 17 years. A tablet-based custom-designed application will be used to capture data from direct assessment of the child and interviews with the main caregiver. In addition, a parallel sub-study will prospectively measure the acute costs of hospitalization due to neonatal sepsis or meningitis, irrespective of underlying etiology. In summary, these data are necessary to characterize the consequences of iGBS disease and enable the advancement of effective strategies for survivors to reach their developmental and economic potential. In particular, our study will inform the development of a full public health value proposition on maternal GBS immunization that is being coordinated by the World Health Organization

Exploiting open source 3D printer architecture for laboratory robotics to automate high-throughput time-lapse imaging for analytical microbiology

Growth in open-source hardware designs combined with the low-cost of high performance optoelectronic and robotics components has supported a resurgence of in-house custom lab equipment development. We describe a low cost (below USD700), open-source, fully customizable high-throughput imaging system for analytical microbiology applications. The system comprises a Raspberry Pi camera mounted on an aluminium extrusion frame with 3D-printed joints controlled by an Arduino microcontroller running open-source Repetier Host Firmware. The camera position is controlled by simple G-code scripts supplied from a Raspberry Pi singleboard computer and allow customized time-lapse imaging of microdevices over a large imaging area. Open-source OctoPrint software allows remote access and control. This simple yet effective design allows high-throughput microbiology testing in multiple formats including formats for bacterial motility, colony growth, microtitre plates and microfluidic devices termed ‘lab-on-a-comb’ to screen the effects of different culture media components and antibiotics on bacterial growth. The open-source robot design allows customization of the size of the imaging area; the current design has an imaging area of ~420 × 300mm, which allows 29 ‘lab-on-a-comb’ devices to be imaged which is equivalent 3480 individual 1μl samples. The system can also be modified for fluorescence detection using LED and emission filters embedded on the PiCam for more sensitive detection of bacterial growth using fluorescent dyes