Trace metal enrichment in a tidally influenced, rural tributary of the upper Chesapeake Bay.

Trace metals in sediments from the Chester River, a tidal tributary of the upper Chesapeake Bay with a predominantly rural, agricultural watershed, were investigated to better understand distributions and potential sources of metals. Sediments were analyzed for Al, Fe, Ni, Cr, Cu, Zn, As, Ag, Cd and organic C. Concentrations exceeded sediment toxicity guidelines in 44% of samples for Pb, and >20% for As, Ni, Cr, and Cu. Median enrichment factors (EF) for Cd, Ag, Pb, As and Zn were elevated above natural background levels. Nickel, Cu, Zn, and Cd exhibited significant differences in EF medians between the upper, middle, and lower segments of the river. Cadmium and As enrichments are presumably from application of inorganic and organic fertilizers in the watershed. Active marinas are likely an important source of metal enrichment, especially for Cu. The data underscore how land use in rural watersheds contributes to metals loading in aquatic systems.

A Nationwide Enumeration of the Surgical Workforce, its Production and Disparities in Operative Productivity in Liberia.

BACKGROUND: Any health care system that strives to deliver good health and well-being to its population relies on a trained workforce. The aim of this study was to enumerate surgical provider density, describe operative productivity and assess the association between key surgical system characteristics and surgical provider productivity in Liberia. METHODS: A nationwide survey of operation theatre logbooks, available human resources and facility infrastructure was conducted in 2018. Surgical providers were counted, and their productivity was calculated based on operative numbers and full-time equivalent positions. RESULTS: A total of 286 surgical providers were counted, of whom 67 were accredited specialists. This translated into a national density of 1.6 specialist providers per 100,000 population. Non-specialist physicians performed 58.3 percent (3607 of 6188) of all operations. Overall, surgical providers performed a median of 1.0 (IQR 0.5-2.7) operation per week, and there were large disparities in operative productivity within the workforce. Most operations (5483 of 6188) were categorized as essential, and each surgical provider performed a median of 2.0 (IQR 1.0-5.0) different types of essential procedures. Surgical providers who performed 7-14 different types of essential procedures were more than eight times as productive as providers who performed 0-1 essential procedure (operative productivity ratio = 8.66, 95% CI 6.27-11.97, P < 0.001). CONCLUSION: The Liberian health care system struggles with an alarming combination of few surgical providers and low provider productivity. Disaggregated data can provide a high-resolution picture of local challenges that can lead to local solutions.

A new sensor based on an amino-montmorillonite-modified inkjet-printed graphene electrode for the voltammetric determination of gentisic acid.

An amperometric sensor based on an inkjet-printed graphene electrode (IPGE) modified with amine-functionalized montmorillonite (Mt-NH2) for the electroanalysis and quantification of gentisic acid (GA) has been developed. The organoclay used as IPGE modifier was prepared and characterized by infrared spectroscopy, X-ray diffraction, scanning electron microscopy, CHN elemental analysis, and thermogravimetry. The electrochemical features of the Mt-NH2/IPGE sensor were investigated by cyclic voltammetry and electrochemical impedance spectroscopy. The sensor exhibited charge selectivity ability which was exploited for the electrochemical oxidation of GA. The GA amperometric response was high in acidic medium (Brinton-Robinson buffer, pH 2) due to favorable interactions between the protonated amine groups and the negatively charged GA. Kinetic studies were also performed by cyclic voltammetry, and the obtained electron transfer rate constant of 11.3 s-1 indicated a fast direct electron transfer rate of GA to the electrode. An approach using differential pulse voltammetry was then developed for the determination of GA (at + 0.233 V vs. a pseudo Ag/Ag+ reference electrode), and under optimized conditions, the sensor showed high sensitivity, a wide working linear range from 1 to 21 µM (R2 = 0.999), and a low detection limit of 0.33 µM (0.051 ± 0.01 mg L-1). The proposed sensor was applied to quantify GA in a commercial red wine sample. The simple and rapid method developed using a cheap clay material could be employed for the determination of various phenolic acids.

Social media and organ donation: Ethically navigating the next frontier.

As the organ shortage continues to grow, the creation of social media communities by transplant hospitals and the public is rapidly expanding to increase the number of living donors. Social media communities are arranged in myriad ways and without standardization, raising concerns about transplant candidates' and potential donors' autonomy and quality of care. Social media communities magnify and modify extant ethical issues in deceased and living donation related to privacy, confidentiality, professionalism, and informed consent, and increase the potential for undue influence and coercion for potential donors and transplant candidates. Currently, no national ethical guidelines have been developed in the United States regarding the use of social media to foster organ transplantation. We provide an ethical framework to guide transplant stakeholders in using social media for public and patient communication about transplantation and living donation, and offer recommendations for transplant clinical practice and future research.

Additive effects of oxytocin receptor gene polymorphisms on reward circuitry in youth with autism.

Several common alleles in the oxytocin receptor gene (OXTR) are associated with altered brain function in reward circuitry in neurotypical adults and may increase risk for autism spectrum disorders (ASD). Yet, it is currently unknown how variation in the OXTR relates to brain functioning in individuals with ASD, and, critically, whether neural endophenotypes vary as a function of aggregate genetic risk. Here, for we believe the first time, we use a multi-locus approach to examine how genetic variation across several OXTR single-nucleotide polymorphisms (SNPs) affect functional connectivity of the brain's reward network. Using data from 41 children with ASD and 41 neurotypical children, we examined functional connectivity of the nucleus accumbens (NAcc) - a hub of the reward network - focusing on how connectivity varies with OXTR risk-allele dosage. Youth with ASD showed reduced NAcc connectivity with other areas in the reward circuit as a function of increased OXTR risk-allele dosage, as well as a positive association between risk-allele dosage and symptom severity, whereas neurotypical youth showed increased NAcc connectivity with frontal brain regions involved in mentalizing. In addition, we found that increased NAcc-frontal cortex connectivity in typically developing youth was related to better scores on a standardized measure of social functioning. Our results indicate that cumulative genetic variation on the OXTR impacts reward system connectivity in both youth with ASD and neurotypical controls. By showing differential genetic effects on neuroendophenotypes, these pathways elucidate mechanisms of vulnerability versus resilience in carriers of disease-associated risk alleles.

What young people with spina bifida want to know about sex and are not being told.

OBJECTIVE: The aim of this paper was to examine sexual knowledge, concerns and needs of youth with spina bifida (SB) to inform the medical community on ways to better support their sexual health. METHODS: As part of the Video Intervention/Prevention Assessment (VIA) - transitions, a prospective cohort study, 309 h of video data were collected from 14 participants (13-28 years old) with SB. Participants were loaned a video camcorder for 8-12 weeks to shoot visual narratives about any aspects of their lives. V/A visual narratives were analysed with grounded theory using NVivo. RESULTS: Out of 14 participants, 11 (six women) addressed issues surrounding romantic relationships and sexuality in their video clips. Analysis revealed shared concerns, questions and challenges regarding sexuality gathered under four main themes: romantic relationships, sexuality, fertility and parenthood, and need for more talk on sexuality. CONCLUSIONS: Youth with SB reported difficulties in finding answers to questions regarding their sexuality, romantic relationships and fertility. This study revealed a need for help from the medical community to inform and empower youth with SB in the area of sexual health. Through sexual and reproductive health education with patients and parents starting at an early age, medical providers can further encourage healthy emotional and physical development in adolescents transitioning into adulthood.

Between Scylla and Charybdis: charting an ethical course for research into financial incentives for living kidney donation.

New approaches to address the kidney scarcity in the United States are urgently needed. The greatest potential source of kidneys is from living donors. Proposals to offer financial incentives to increase living kidney donation rates remain highly controversial. Despite repeated calls for a pilot study to assess the impact of financial compensation on living kidney donation rates, many fear that financial incentives will exploit vulnerable individuals and cast the field of transplantation in a negative public light, ultimately reducing donation rates. This paper provides an ethical justification for conducting a pilot study of a federally regulated approach to providing financial incentives to living kidney donors, with the goal of assessing donors' perceptions.

Does financial compensation for living kidney donation change willingness to donate?

The potential use of financial compensation to increase living kidney donation rates remains controversial in potentially introducing undue inducement of vulnerable populations to donate. This cross-sectional study assessed amounts of financial compensation that would generate motivation and an undue inducement to donate to family/friends or strangers. Individuals leaving six Departments of Motor Vehicles were surveyed. Of the 210 participants who provided verbal consent (94% participation rate), respondents' willingness to donate would not change (70%), or would increase (29%) with compensation. Median lowest amounts of financial compensation for which participants would begin to consider donating a kidney were $5000 for family/friends, and $10,000 for strangers; respondents reporting $0 for family/friends (52%) or strangers (26%) were excluded from analysis. Median lowest amounts of financial compensation for which participants could no longer decline (perceive an undue inducement) were $50,000 for family/friends, and $100,000 for strangers; respondents reporting $0 for family/friends (44%) or strangers (23%) were excluded from analysis. The two most preferred forms of compensation included: direct payment of money (61%) and paid leave (21%). The two most preferred uses of compensation included: paying off debt (38%) and paying nonmedical expenses associated with the transplant (29%). Findings suggest tolerance for, but little practical impact of, financial compensation. Certain compensation amounts could motivate the public to donate without being perceived as an undue inducement.

Functional and symptom impact of trametinib versus chemotherapy in BRAF V600E advanced or metastatic melanoma: quality-of-life analyses of the METRIC study.

BACKGROUND: In a randomized phase III study, trametinib prolonged progression-free survival and improved overall survival versus chemotherapy in patients with BRAF V600 mutation-positive melanoma. PATIENTS AND METHODS: Patients' quality of life (QOL) was assessed at baseline and follow-up visits using the European Organisation for Research and Treatment of Cancer Core QOL questionnaire. RESULTS: In the primary efficacy population (BRAF V600E+, no brain metastases) from baseline to weeks 6 and 12, patients' global health status scores worsened by 4-5 points with chemotherapy but improved by 2-3 points with trametinib. Rapid and substantive reductions in QOL functionality (e.g. role functioning, 8-11 points at weeks 6 and 12) and symptom exacerbation (e.g. fatigue, 4-8 points; nausea and vomiting, 5 points, both at weeks 6 and 12) were observed in chemotherapy-treated patients. In contrast, trametinib-treated patients reported small improvements or slight worsening from baseline at week 12, depending on the functional dimension and symptom. The mean symptom-scale scores for chemotherapy-treated patients increased from baseline (symptoms worsened) for seven of eight symptoms at week 6 (except insomnia) and six of eight symptoms at week 12 (except dyspnea and insomnia). In contrast, at weeks 6 and 12, the mean symptom-scale scores for trametinib decreased from baseline (symptoms improved) for pain (11-12 points), insomnia (10-12 points), and appetite loss (1-5 points), whereas those for diarrhea worsened (15-16 points). Mixed-model repeated-measures analyses showed significant (P < 0.05) and/or clinically meaningful improvements (small to moderate) from baseline in favor of trametinib for global health; physical, role, and social functioning; fatigue; pain; insomnia; nausea and vomiting; constipation; dyspnea; and appetite at weeks 6 and/or 12. QOL results for the intent-to-treat population were consistent. CONCLUSIONS: This first QOL assessment for a MEK inhibitor in metastatic melanoma demonstrated that trametinib was associated with less functional impairment, smaller declines in health status, and less exacerbation of symptoms versus chemotherapy.

Opportunities for shared decision making in kidney transplantation.

Health researchers and policy-makers increasingly urge both patient and clinician engagement in shared decision making (SDM) to promote patient-centered care. Although SDM has been examined in numerous clinical settings, it has received little attention in solid organ transplantation. This paper describes the application of SDM to the kidney transplantation context. Several distinctive features of kidney transplantation present challenges to SDM including fragmented patient-provider relationships, the time-sensitive and unpredictable nature of deceased organ offers, decision-making processes by transplant providers serving as both organ guardians (given the organ scarcity) versus advocates for specific patients seeking transplantation, variable clinical practices and policies among transplant centers, and patients' potentially compromised cognitive status and literacy levels. We describe potential barriers to and opportunities for SDM, and posit that SDM is feasible, warranting encouragement in kidney transplantation. We propose strategies to promote and overcome obstacles to SDM in kidney transplantation. We contend that engagement in SDM can be facilitated by re-organization of clinical care, communication and education of providers and patients.

The challenge of informed consent for increased risk living donation and transplantation.

The Organ Procurement and Transplantation Network (OPTN) mandates that organ recipients provide "specific informed consent" before accepting organs that the OPTN defines as "increased risk". However, the OPTN does not provide specific guidelines for what information should be disclosed to potential recipients. Such vagueness opens the door to inadequate informed consent. This paper examines the ethical dimensions of informed consent when the prospective living donor has self-reported behaviors associated with increased risk for infection transmission. Donor privacy is a primary ethical concern that conflicts with recipients' informed consent for use of increased risk organs. We propose that both the increased risk status and the specific behavior be disclosed to the recipient. Because the actual risk posed is linked to the type of risk behavior, disclosure is therefore needed to make an informed decision. The donor's risk behavior is material to recipients' decision making because it may impact the donor-recipient relationship. This relationship is the foundation of the donation and acceptance transaction, and thus comprises a critical feature of the recipient's informed consent. Optimizing a recipient's informed consent is essential to protecting patient safety and autonomy.

[Characteristics of ischemic stroke in patients with congenital anomalies of the circle of Willis].

The study included 76 patients with ischemic stroke in the carotid system (56 patients) and in the vertebrobasilar system (20 patients). The magnetic resonance angiography (MRA) revealed congenital anomalies of Willis circle in 31 patients. These anomalies were stratified as follows: back trifurcation of the internal carotid artery (ICA) (19 patients), anterior trifurcation of the ICA (4 patients), the combination of anterior trifurcation of the one of ICA and posterior trifurcation of the other ICA (4 patients), double back trifurcation of ICA (2 patients), the normal structure of the circle of Willis (45 patients). Patients with anomalies of the circle of Willis scored significantly higher on the Neurological deficit scale NIH-NINDS. Despite the lack of significant differences in the size of lesions in 2 groups, the foci in patients with the abnormalities of the circle of Willis were frequently localized in adjacent blood supply zones. The signs of vascular encephalopathy were seen as well. The data obtained suggest that the presence of anomalies in the circle of Willis is a risk factor, together with in the additional adversities, including iatrogenic factor, for the development of hemodynamic ischemic stroke.

The immortalizing and transforming ability of two common human papillomavirus 16 E6 variants with different prevalences in cervical cancer.

Persistent infection with high-risk human papillomaviruses (HPVs), especially type 16 has been undeniably linked to cervical cancer. The Asian-American (AA) variant of HPV16 is more common in the Americas than the prototype in cervical cancer. The different prevalence is based on three amino acid changes within the E6 protein denoted Q14H/H78Y/L83V. To investigate the mechanism(s) behind this observation, both E6 proteins, in the presence of E7, were evaluated for their ability to extend the life span of and transform primary human foreskin keratinocytes (PHFKs). Long-term cell culture studies resulted in death at passage 9 of vector-transduced PHFKs (negative control), but survival of both E6 PHFKs to passage 65 (and beyond). Compared with E6/E7 PHFKs, AA/E7 PHFKs were significantly faster dividing, developed larger cells in monolayer cultures, showed double the epithelial thickness and expressed cytokeratin 10 when grown as organotypic raft cultures. Telomerase activation and p53 inactivation, two hallmarks of immortalization, were not significantly different between the two populations. Both were resistant to anoikis at later passages, but only AA/E7 PHFKs acquired the capacity for in vitro transformation. Proteomic analysis revealed markedly different protein patterns between E6/E7 and AA/E7, particularly with respect to key cellular metabolic enzymes. Our results provide new insights into the reasons underlying the greater prevalence of the AA variant in cervical cancer as evidenced by characteristics associated with higher oncogenic potential.

HPV16 E6 oncoprotein increases cell adhesion in human keratinocytes.

Expression of the E6 oncoprotein of human papillomavirus (HPV) 16 in primary human keratinocytes (PHKs) was previously shown to significantly reduce apoptosis. This could be due to increased cell adhesion. Adhesion ability was tested by seeding cells on tissue culture dishes coated with different concentrations of poly(HEME) and determination of the proportion of attached cells. Assays were carried out with PHKs, immortalized human keratinocytes (HaCaT) and human 293T cells. The E6 gene was transduced via retroviral infection or DNA transfection. Results of these assays showed that expression of E6 increased the proportion of cells that attached to poly(HEME). Several HPV16 E6 mutants were also tested in the above assay in 293T cells. These assays showed that the p53 targeting region of E6 is dispensable for this activity. Assays of inhibition of tyrosine kinases by bombesin showed that E6 probably utilizes other pathways to increase cell adhesion.

[To the mechanism of edema around malignant brain glioma].

Based on the results of a comparative study (magnetic resonance imaging and/or computed tomography with a morphological study) in 11 patients with malignant brain glioma, the authors have ascertained that the extent of perifocal edema cannot fully reflect the degree of impairment of the blood-brain barrier (BBB) in the tumor vessels: the signs of BBB impairment were found in 47.1% of the tumor vessels in patients with insignificant edema and in only 15% of the vessels in those with significant edema.

[Magnetic resonance imaging in the diagnosis and treatment of hernias of thoracic intervertebral disks].

Magnetic resonance imaging (MRI) was carried out in 24 patients with thoracic osteochondrosis. The obtained MR images showed the high efficiency of this radiodiagnostic technique in solving the tasks of visualizing a degenerative-dystrophic lesion of the vertebral column. MRI allows one to solve a broad spectrum of specific problems facing a radiodiagnostician and a neurosurgeon on examining a patient with thoracic osteochondrosis. This study permits an objective assessment of the stage of herniation and the degree of spinal cord compression, determination of treatment policy, planning of a surgical intervention, assessment of the results of surgical treatment, timely detection of possible complications, and visualization of recurrent hernia.