In vivo imaging and characterization of hypoxia-induced neovascularization and tumor invasion

Hypoxia is a critical event in tumor progression and angiogenesis. Hypoxia can be detected noninvasively by a novel spectroscopic photoacoustic tomography technology (SPAT) and this finding is supported by our molecular biology investigation aimed to elucidate the etiopathogenesis of SPAT detected hypoxia and angiogenesis. The present study provides an integrated approach to define oxygen status (hypoxia) of intracranial tumor xenografts using spectroscopic photoacoustic tomography. Brain tumors can be identified based on their distorted vascular architecture and oxygen saturation (SO2) images. Noninvasive in vivo tumor oxygenation imaging using SPAT is based on the spectroscopic absorption differences between oxyhemoglobin (O2Hb) and deoxyhemoblobin (HHb). Sprague-Dawley rats inoculated intracranially with ENU1564, a carcinogen-induced rat mammary adenocarcinoma cell line, were imaged with SPAT three weeks post inoculation. Proteins important for tumor angiogenesis and invasion were detected in hypoxic brain foci identified by SPAT and were elevated compared with control brain. Immunohistochemistry, Western blotting, and semi-quantitative RT-PCR showed that HIF-1 α, VEGF-A, and VEGFR2 (Flk-1) protein and mRNA expression levels were significantly higher (P<0.05) in brain tumor tissues compared to normal brain. Gelatin zymography and RT-PCR demonstrated the upregulation of MMP-9 in tumor foci compared with brain control. Together these results suggest the critical role of hypoxia in driving tumor angiogenesis and invasion through upregulation of target genes important for these functions. Moreover this report validates our hypothesis that a novel noninvasive technology (SPAT) developed in our laboratory is suitable for detection of tumors, hypoxia, and angiogenesis

Electromyographic and Joint Kinematic Patterns in Runner\u27s Dystonia.

Runner’s dystonia (RD) is a task-specific focal dystonia of the lower limbs that occurs when running. In this retrospective case series, we present surface electromyography (EMG) and joint kinematic data from thirteen patients with RD who underwent instrumented gait analysis (IGA) at the Functional and Biomechanics Laboratory at the National Institutes of Health. Four cases of RD are described in greater detail to demonstrate the potential utility of EMG with kinematic studies to identify dystonic muscle groups in RD. In these cases, the methodology for muscle selection for botulinum toxin therapy and the therapeutic response is discussed. Lateral heel whip, a proposed novel presentation of lower-limb dystonia, is also described

Nursing and midwifery students\u27 experiences and perception of their clinical learning environment in Malawi: A mixed-method study

© 2020 The Author(s). Background: The clinical learning environment is an important part of the nursing and midwifery training as it helps students to integrate theory into clinical practice. However, not all clinical learning environments foster positive learning. This study aimed to assess the student nurses and midwives\u27 experiences and perception of the clinical learning environment in Malawi. Methods: A concurrent triangulation mixed methods research design was used to collect data from nursing and midwifery students. Quantitative data were collected using a Clinical Learning Environment Inventory, while qualitative data were collected using focus group discussions. The Clinical Learning Environment Inventory has six subscales of satisfaction, involvement, individualisation, innovation, task orientation and personalisation. The focus group interview guide had questions about clinical learning, supervision, assessment, communication and resources. Quantitative data were analysed by independent t-test and multivariate linear regression and qualitative data were thematically analysed. Results: A total of 126 participants completed the questionnaire and 30 students participated in three focus group discussions. Satisfaction subscale had the highest mean score (M = 26.93, SD = 4.82) while individualisation had the lowest mean score (M = 18.01, SD =3.50). Multiple linear regression analysis showed a statistically significant association between satisfaction with clinical learning environment and personalization (β = 0.50, p = \u3c 0.001), and task orientation (β =0.16 p = \u3c 0.05). Teaching and learning resources, hostile environment, poor relationship with a qualified staff, absence of clinical supervisors, and lack of resources were some of the challenges faced by students in their clinical learning environment. Conclusion: Although satisfaction with clinical learning environment subscale had the highest mean score, nursing and midwifery students encountered multifaceted challenges such as lack of resources, poor relationship with staff and a lack of support from clinical teachers that negatively impacted on their clinical learning experiences. Training institutions and hospitals need to work together to find means of addressing the challenges by among others providing resources to students during clinical placement

Substance use and HIV infection awareness among HIV-infected female sex workers in Lilongwe, Malawi

HIV diagnosis, the first step in HIV care and treatment engagement, may be inhibited by substance use among female sex workers (FSW). We assessed the relationship between alcohol and marijuana use and lack of HIV infection awareness among HIV-infected FSW in Lilongwe, Malawi

The HIV Care Continuum among Female Sex Workers: A Key Population in Lilongwe, Malawi

ObjectiveThe HIV care continuum among female sex workers (FSW), a key population, has not been well characterized, especially within the generalized epidemics of sub-Saharan Africa. This was the first study to characterize the HIV care continuum among FSW in Lilongwe, Malawi.MethodsFrom July through September 2014, we used venue-based sampling to enroll 200 adult FSW in Lilongwe, Malawi into a cross-sectional evaluation assessing HIV care continuum outcomes. Seropositive FSW, identified using HIV rapid testing, received rapid CD4 counts in addition to viral loads using dried blood spots. We calculated proportions of HIV-infected FSW who had history of care, were on ART, and had suppressed viral load and we used Poisson regression to estimate the associations of demographic characteristics and transmission risk behaviors with each outcome.ResultsHIV seroprevalence was 69% (n = 138). Among all FSW the median age was 24 years (IQR: 22–28). Among the 20% who were newly diagnosed and reported previously testing negative, the median time since last HIV test was 11 months (interquartile range: 3–17). The majority (69%) of HIV-infected FSW had a history of HIV care, 52% reported current ART use, and 45% were virally suppressed. Of the FSW who reported current ART use, 86% were virally suppressed. Transmission risk behaviors were not associated with continuum outcomes.ConclusionsFSW in Lilongwe were predominately young and have a high HIV prevalence. Only half of HIV-infected FSW reported current ART use, but the majority of those on ART were virally suppressed. To reduce ongoing transmission and improve health outcomes, increased HIV testing, care engagement, and ART coverage is urgently needed among FSW. Universal testing and treatment strategies for all FSW in Malawi must be strongly considered

Photoacoustic molecular imaging of small animals in vivo

Molecular imaging is a newly emerging field in which the modern tools of molecular and cell biology have been married to state-of-the-art technologies for noninvasive imaging. The study of molecular imaging will lead to better methods for understanding biological processes as well as diagnosing and managing disease. Here we present noninvasive in vivo spectroscopic photoacoustic tomography (PAT)-based molecular imaging of αvβ3 integrin in a nude mouse U87 brain tumor. PAT combines high optical absorption contrast and high ultrasonic resolution by employing short laser pulses to generate acoustic waves in biological tissues through thermoelastic expansion. Spectroscopic PAT-based molecular imaging offers the separation of the contributions from different absorbers based on the differences in optical absorption spectra among those absorbers. In our case, in the near infrared (NIR) range, oxy-heamoglobin (O2Hb), deoxy-heamoglobin (HHb) and the injected αvβ3-targeted peptide-ICG conjugated NIR fluorescent contrast agent are the three main absorbers. Therefore, with the excitation by multiple wavelength laser pulses, spectroscopic PAT-based molecular imaging not only provides the level of the contrast agent accumulation in the U87 glioblastoma tumor, which is related to the metabolism and angiogenesis of the tumor, but also offers the information on tumor angiogenesis and tumor hypoxia

Socioecological Factors Related to Hazardous Alcohol use among Female Sex Workers in Lilongwe, Malawi: A Mixed Methods Study

Background: Alcohol use is pervasive among female sex workers (FSW) placing them at increased risk of violence and sexual risk behaviors. FSW often live and work where alcohol is highly normative. Objective: To understand the socioecological influences on hazardous alcohol use among FSW in Malawi. Methods: In 2014, 200 FSW identified through venue-based sampling in Lilongwe, Malawi, completed a quantitative behavioral survey, with a sub-sample participating in qualitative interviews. Multivariable log-binomial regression was used to identify associations between hazardous alcohol use (AUDIT score ≥ 7) and time in sex work, clients per week, unprotected sex, alcohol use with clients, and living environment. Qualitative interviews enhanced findings from quantitative data and identify emergent themes around socioecological influences on alcohol use. Results: Over 50% reported hazardous alcohol use and lived in an alcohol-serving venue. Hazardous alcohol use was associated with sex work duration of ≥2 years (aPR: 1.30; 95%CI: 1.02,1.65) and alcohol use at last sex with a client (aPR: 1.29; 95%CI: 1.06,1.57). FSW perceived alcohol as a facilitator for sex work by reducing inhibitions and attracting clients, but acknowledged alcohol leads to violence and/or unprotected sex. Despite these risks and a motivation to reduce use, FSW feared that refusing to drink would be tantamount to turning away clients. Conclusions: Although FSW recognized alcohol-related risks, the norms and power dynamics of sex work perpetuated hazardous alcohol use. Multilevel interventions are needed to collectively change norms around drinking and sex work that will enable FSW to reduce alcohol consumption when engaging in their work