Malaria is a major cause of illness worldwide. In a phase 2 trial in Mali, one subcutaneous dose of L9LS, a monoclonal antibody targeting
Plasmodium falciparum
, reduced the incidence of clinical ...malaria among children.
Adverse patient events are inevitable in surgical practice.
To characterize the impact of adverse patient events on surgeons and trainees, identify coping mechanisms, and assess whether current forms ...of support are sufficient.
In this mixed-methods study, a validated survey instrument was adapted and distributed to surgical trainees from 7 programs, and qualitative interviews were conducted with faculty from 4 surgical departments in an urban academic health system.
The personal impact of adverse patient events, current coping mechanisms, and desired forms of support.
Of 216 invited trainees, 93 (43.1%) completed the survey (49 52.7% male; 60 64.5% in third postgraduate year or higher; 23 24.7% Asian or Pacific Islander, 6 6.5% Black, 51 54.8% White, and 8 8.6% other race; 13 14.0% Hispanic or Latinx ethnicity). Twenty-three of 29 (79.3%) invited faculty completed interviews (13 56.5% male; median IQR years in practice, 11.0 7.5-20.0). Of the trainees, 77 (82.8%) endorsed involvement in at least 1 recent adverse event. Most reported embarrassment (67 of 79 trainees 84.8%), rumination (64 of 78 trainees 82.1%), and fear of attempting future procedures (51 of 78 trainees 65.4%); 28 of 78 trainees (35.9%) had considered quitting. Female trainees and trainees who identified as having a race and/or ethnicity other than non-Hispanic White consistently reported more negative consequences compared with male and White trainees. The most desired form of support was the opportunity to discuss the incident with an attending physician (76 of 78 respondents 97.4%). Similarly, faculty described feelings of guilt and shame, loss of confidence, and distraction after adverse events. Most described the utility of confiding in peers and senior colleagues, although some expressed unwillingness to reach out. Several suggested designating a departmental point person for event debriefing.
In this mixed-methods study of the personal impact of adverse events on surgeons and trainees, these events were nearly universally experienced and caused significant distress. Providing formal support mechanisms for both surgical trainees and faculty may decrease stigma and restore confidence, particularly for underrepresented groups.
OBJECTIVE:To evaluate the safety and immunogenicity of a candidate HIV DNA vaccine administered using a needle-free device.
DESIGN:In this phase 1, dose escalation, double-blind, placebo-controlled ...clinical trial, 21 healthy adults were randomized to receive placebo or 0.5, 1.5, or 4 mg of a single plasmid expressing a Gag/Pol fusion protein. Each participant received repeat immunizations at days 28 and 56 after the first inoculation. Safety and immunogenicity data were collected.
RESULTS:The vaccine was well tolerated, with most adverse events being mild injection site reactions, including pain, tenderness, and erythema. No dose-limiting toxicities occurred. HIV-specific antibody response was not detected in any vaccinee by enzyme-linked immunosorbent assay. HIV-specific T-cell responses to Gag or Pol as measured by enzyme-linked immunospot assay and intracellular cytokine staining were of low frequency and magnitude.
CONCLUSIONS:This candidate HIV DNA vaccine was safe and well tolerated. No HIV-specific antibody responses were detected, and only low-magnitude HIV-specific T-cell responses were detected in 8 (53%) of 15 vaccinees. This initial product led to the development of a 4-plasmid multiclade HIV DNA Vaccine Research Center vaccine candidate in which envelope genes expressing Env from clades A, B, and C and a Nef gene from clade B have been added.
A Monoclonal Antibody for Malaria Prevention Gaudinski, Martin R; Berkowitz, Nina M; Idris, Azza H ...
The New England journal of medicine,
08/2021, Letnik:
385, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Malaria remains a cause of substantial global morbidity and mortality. In this report, an engineered monoclonal antibody showed protection against malaria infection in a controlled human infection ...model.
Human microvascular endothelial cells (HMVEC) from adult adipose tissue were cultured in MCDB 131 medium supplemented with 10% fetal bovine serum. Under these conditions, HMVEC from seven different ...donors had finite proliferative life spans ranging from 14.5 to 23.5 population doublings (PD), with a mean life span of 19 PD. Addition of 10% conditioned medium from activated human leukocyte cultures (BM CondimedREGESTERERED TRADE MARK SIZNE) extended the life span of HMVEC to 31 to 41 PD, with a mean life span of 37 PD. At the end of lifespan, HMVEC cultures both with and without BM Condimed had very low labeling indices (0 to 5% 3Hthymidine labeled nuclei) and consisted of enlarged cells. However, the morphologies of the two types of HMVEC cultures were very different. Untreated HMVEC were polygonal endothelial cells that formed cobblestonelike monolayers with no cell overlapping. In contrast, BM Condimed-treated HMVEC were more elongated, less regularly shaped cells that were not strictly inhibited from overlapping. When old, these cells accumulated numerous vacuoles. The BM Condimed-treated HMVEC expressed Factor VIII antigen, which confirms their identity as endothelial cells. These cells reverted rapidly to the polygonal morphology of untreated HMVEC when they were removed from BM Condimed. Likewise, their proliferative capacity was not extended further once BM Condimed was removed. These results suggest that HMVEC can exist in two distinct morphologic states in which the cells have different finite proliferative life spans.
Influence of HLA-C Expression Level on HIV Control Apps, Richard; Qi, Ying; Carlson, Jonathan M. ...
Science (American Association for the Advancement of Science),
04/2013, Letnik:
340, Številka:
6128
Journal Article
Recenzirano
Odprti dostop
A variant upstream of human leukocyte antigen C (HLA-C) shows the most significant genome-wide effect on HIV control in European Americans and is also associated with the level of HLA-C expression. ...We characterized the differential cell surface expression levels of all common HLA-C allotypes and tested directly for effects of HLA-C expression on outcomes of HIV infection in 5243 individuals. Increasing HLA-C expression was associated with protection against multiple outcomes independently of individual HLA atlelic effects in both African and European Americans, regardless of their distinct HLA-C frequencies and linkage relationships with HLA-B and HLA-A. Higher HLA-C expression was correlated with increased likelihood of cytotoxic T lymphocyte responses and frequency of viral escape mutation. In contrast, high HLA-C expression had a deleterious effect in Crohn's disease, suggesting a broader influence of HLA expression levels in human disease.
●Global neuroimaging genetics collaborations have been formed to pool and compare brain data and replicate study findings.●There have been few substantive discussions of the ethical issues raised by ...global neuroimaging genetics collaborations.●While such collaborations have many potential benefits, there are concerns regarding inequity, exploitation and data sharing.●In particular, the issue of feedback of findings and the risk of stigma, in certain contexts, must be addressed.●The principle of solidarity may be a useful resource in addressing some of the issues raised above.
Neuroimaging genetics is a rapidly developing field that combines neuropsychiatric genetics studies with imaging modalities to investigate how genetic variation influences brain structure and function. As both genetic and imaging technologies improve further, their combined power may hold translational potential in terms of improving psychiatric nosology, diagnosis, and treatment. While neuroimaging genetics studies offer a number of scientific advantages, they also face challenges. In response to some of these challenges, global neuroimaging genetics collaborations have been created to pool and compare brain data and replicate study findings. Attention has been paid to ethical issues in genetics, neuroimaging, and multi-site collaborative research, respectively, but there have been few substantive discussions of the ethical issues generated by the confluence of these areas in global neuroimaging genetics collaborations. Our discussion focuses on two areas: benefits and risks of global neuroimaging genetics collaborations and the potential impact of neuroimaging genetics research findings in low- and middle-income countries. Global neuroimaging genetics collaborations have the potential to enhance relations between countries and address global mental health challenges, however there are risks regarding inequity, exploitation and data sharing. Moreover, neuroimaging genetics research in low- and middle-income countries must address the issue of feedback of findings and the risk of essentializing and stigmatizing interpretations of mental disorders. We conclude by examining how the notion of solidarity, informed by an African Ethics framework, may justify some of the suggestions made in our discussion.
PDF
