The Community is the Cure: How African American Washington, DC Residents Informed Opioid Treatment Engagement.

BACKGROUND: Recent data indicate rising opioid overdose deaths among African American residents of Washington, DC. OBJECTIVES: We highlight a community-informed approach to assessing attitudes toward opioid use disorder treatment among DC residents (February 2019 to March 2020). METHODS: A listening tour with trusted community leaders led to the formation of a Community Advisory Board (CAB). When the COVID-19 pandemic commenced in March 2020, community dialogues became exclusively virtual. The CAB partnered with academic leaders to co-create project mission and values and center the community's concerns related to opioid use and its causes, treatment structure, and facilitators of effective engagement. RESULTS: Interview guides were created for the engagement of community members, using values highlighted by the CAB. The CAB underscored that in addition to opioid problems, effective engagement must address community experience, collective strengths/resilience, and the role of indigenous leadership. CONCLUSIONS: Engaging community prior to project implementation and maintaining alignment with community values facilitated opioid use disorder assessments. Community-informed assessments may be critical to building community trust.

Pan-viral Antibody Repertoire of Aqueous Humor in Cytomegalovirus Uveitis.

PURPOSE: The identification of infectious etiologies is important in the management of uveitis. Ocular fluid testing is required, but multiplex testing faces challenges due to the limited volume sampled. The determination of antibody repertoire of aqueous humor (AH) is not possible with conventional assays. We investigated the use of a highly multiplexable serological assay VirScan, a Phage ImmunoPrecipitation Sequencing (PhIP-Seq) library derived from the sequences of more than 200 viruses to determine the antibody composition of AH in patients with uveitis. DESIGN: Prospective, case control study. METHODS: We analyzed the paired AH and plasma samples of 11 immunocompetent patients with active polymerase chain reaction-positive cytomegalovirus (CMV) anterior uveitis and the AH of 34 control patients undergoing cataract surgery with no known uveitis in an institutional practice. The samples were tested using VirScan PhIP-Seq, and the entire pan-viral antibody repertoire was determined using peptide tile ranking by normalized counts to identify significant antibodies enrichment against all viruses with human tropism. RESULTS: Significant enrichment of antibodies to Herpesviridae, Picornavirdae, and Paramyxoviridae was detectable in 20 µL of AH samples from patients with CMV uveitis and controls. Patients with CMV uveitis had relative enrichment of anti-CMV antibodies in AH compared with their plasma. Epitope-level mapping identified significant enrichment of antibodies against CMV tegument protein pp150 (P = 1.5e-06) and envelope glycoprotein B (P = .0045) in the AH compared with controls. CONCLUSIONS: Our proof-of-concept study not only sheds light on the antibody repertoire of AH but also expands the utility of PhIP-Seq to future studies to detect antibodies in AH in the study of inflammatory eye diseases.

Mentoring approaches in a safe surgery program in Tanzania: Lessons learned during COVID-19 and recommendations for the future.

Background: COVID-19 has dramatically affected the delivery of health care and technical assistance. This is true in Tanzania, where maternal mortality and surgical infection rates are significantly higher than in high-income countries. This paper describes lessons learned about the optimal application of in-person and virtual mentorship in the Safe Surgery 2020 program to improve the quality of surgical services in Tanzania before and after the COVID-19 pandemic. Methods: From January 2018 through December 2020, Safe Surgery 2020 supported 40 health facilities in Tanzania's Lake Zone to improve the quality of surgical care. A blended surgical mentorship model, employing both onsite and virtual mentorship, was central to the program's capacity development approach. With COVID-19, the program pivoted to full virtual mentorship. Through continuous learning and adaptation processes, including a human-centered design workshop, surveys assessing mentors' confidence with different competencies, and focus group discussions with mentors, mentees and safe surgery program staff, the program distilled the optimal use of mentorship models. Results: Developing complex surgical skills, addressing contextual considerations, problem-solving, and building trusting relationships were best suited to in-person mentorship, whereas virtual mentorship was most effective in supporting mentees' quality improvement projects, data use, case discussions, and reinforcing clinical practices. Leading successful virtual learning required enhanced facilitation skills and active engagement of health facility leadership. Conclusions: In-person and virtual mentorship offer distinct benefits and complement each other when combined. Investing more in-person mentorship at the beginning of programs allows for the establishment of trust that is foundational to effective mentorship.

Phage ImmunoPrecipitation Sequencing (PhIP-Seq): The Promise of High Throughput Serology.

Phage ImmunoPrecipitation Sequencing (PhIP-Seq) is a high throughput serological technology that is revolutionizing the manner in which we track antibody profiles. In this review, we mainly focus on its application to viral infectious diseases. Through the pull-down of patient antibodies using peptide-tile-expressing T7 bacteriophages and detection using next-generation sequencing (NGS), PhIP-Seq allows the determination of antibody repertoires against peptide targets from hundreds of proteins and pathogens. It differs from conventional serological techniques in that PhIP-Seq does not require protein expression and purification. It also allows for the testing of many samples against the whole virome. PhIP-Seq has been successfully applied in many infectious disease investigations concerning seroprevalence, risk factors, time trends, etiology of disease, vaccinology, and emerging pathogens. Despite the inherent limitations of this technology, we foresee the future expansion of PhIP-Seq in both investigative studies and tracking of current, emerging, and novel viruses. Following the review of PhIP-Seq technology, its limitations, and applications, we recommend that PhIP-Seq be integrated into national surveillance programs and be used in conjunction with molecular techniques to support both One Health and pandemic preparedness efforts.

A multimodal mentorship intervention to improve surgical quality in Tanzania's Lake Zone: a convergent, mixed methods assessment.

BACKGROUND: Safe, high-quality surgical care in many African countries is a critical need. Challenges include availability of surgical providers, improving quality of care, and building workforce capacity. Despite growing evidence that mentoring is effective in African healthcare settings, less is known about its role in surgery. We examined a multimodal approach to mentorship as part of a safe surgery intervention (Safe Surgery 2020) to improve surgical quality. Our goal was to distill lessons for policy makers, intervention designers, and practitioners on key elements of a successful surgical mentorship program. METHODS: We used a convergent, mixed-methods design to examine the experiences of mentees, mentors, and facility leaders with mentorship at 10 health facilities in Tanzania's Lake Zone. A multidisciplinary team of mentors worked with surgical providers over 17 months using in-person mentorship, telementoring, and WhatsApp. We conducted surveys, in-depth interviews, and focus groups to capture data in four categories: (1) satisfaction with mentorship; (2) perceived impact; (3) elements of a successful mentoring program; and (4) challenges to implementing mentorship. We analyzed quantitative data using frequency analysis and qualitative data using the constant comparison method. Recurrent and unifying concepts were identified through merging the qualitative and quantitative data. RESULTS: Overall, 96% of mentees experienced the intervention as positive, 88% were satisfied, and 100% supported continuing the intervention in the future. Mentees, mentors, and facility leaders perceived improvements in surgical practice, the surgical ecosystem, and in reducing postsurgical infections. Several themes related to the intervention's success emerged: (1) the intervention's design, including its multimodality, side-by-side mentorship, and standardization of practices; (2) the mentee-mentor relationship, including a friendly, safe, non-hierarchical, team relationship, as well as mentors' understanding of the local context; and (3) mentorship characteristics, including non-judgmental feedback, experience, and accessibility. Challenges included resistance to change, shortage of providers, mentorship dose, and logistics. CONCLUSIONS: Our study suggests a multimodal mentorship approach is promising in building the capacity of surgical providers. By distilling the experiences of the mentees, mentors, and facility leaders, our lessons provide a foundation for future efforts to establish effective surgical mentorship programs that build provider capacity and ultimately improve surgical quality.

Pulmonary T-cell lymphoma masquerading as eosinophilic pneumonitis.

Primary pulmonary T-cell lymphoma is an unusual subtype of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). This is a general term used to describe a diverse group of T-cell-type lymphomas that would otherwise not be classified as a PTCL. Among non-Hodgkin's lymphomas, PTCL accounts for 12% of cases. PTCL-NOS accounts for approximately 25% of all PTCL cases. Primary pulmonary T-cell lymphoma is associated with unfavorable outcomes and has a poor prognosis. Being a rare disease, epidemiological data regarding primary pulmonary T-cell lymphoma continues to be sparse at this time. We present a case of PTCL, which was misdiagnosed as eosinophilic pneumonitis (EP) based on samples obtained from transbronchial cryobiopsy. To our knowledge, this is the first reported case of PTCL masquerading as EP.

Shape and Size Control of Artificial Cells for Bottom-Up Biology.

Bottom-up biology is an expanding research field that aims to understand the mechanisms underlying biological processes via in vitro assembly of their essential components in synthetic cells. As encapsulation and controlled manipulation of these elements is a crucial step in the recreation of such cell-like objects, microfluidics is increasingly used for the production of minimal artificial containers such as single-emulsion droplets, double-emulsion droplets, and liposomes. Despite the importance of cell morphology on cellular dynamics, current synthetic-cell studies mainly use spherical containers, and methods to actively shape manipulate these have been lacking. In this paper, we describe a microfluidic platform to deform the shape of artificial cells into a variety of shapes (rods and discs) with adjustable cell-like dimensions below 5 µm, thereby mimicking realistic cell morphologies. To illustrate the potential of our method, we reconstitute three biologically relevant protein systems (FtsZ, microtubules, collagen) inside rod-shaped containers and study the arrangement of the protein networks inside these synthetic containers with physiologically relevant morphologies resembling those found in living cells.

Designer synthetic media for studying microbial-catalyzed biofuel production.

BACKGROUND: The fermentation inhibition of yeast or bacteria by lignocellulose-derived degradation products, during hexose/pentose co-fermentation, is a major bottleneck for cost-effective lignocellulosic biorefineries. To engineer microbial strains for improved performance, it is critical to understand the mechanisms of inhibition that affect fermentative organisms in the presence of major components of a lignocellulosic hydrolysate. The development of a synthetic lignocellulosic hydrolysate (SH) media with a composition similar to the actual biomass hydrolysate will be an important advancement to facilitate these studies. In this work, we characterized the nutrients and plant-derived decomposition products present in AFEX™ pretreated corn stover hydrolysate (ACH). The SH was formulated based on the ACH composition and was further used to evaluate the inhibitory effects of various families of decomposition products during Saccharomyces cerevisiae 424A (LNH-ST) fermentation. RESULTS: The ACH contained high levels of nitrogenous compounds, notably amides, pyrazines, and imidazoles. In contrast, a relatively low content of furans and aromatic and aliphatic acids were found in the ACH. Though most of the families of decomposition products were inhibitory to xylose fermentation, due to their abundance, the nitrogenous compounds showed the most inhibition. From these compounds, amides (products of the ammonolysis reaction) contributed the most to the reduction of the fermentation performance. However, this result is associated to a concentration effect, as the corresponding carboxylic acids (products of hydrolysis) promoted greater inhibition when present at the same molar concentration as the amides. Due to its complexity, the formulated SH did not perfectly match the fermentation profile of the actual hydrolysate, especially the growth curve. However, the SH formulation was effective for studying the inhibitory effect of various compounds on yeast fermentation. CONCLUSIONS: The formulation of SHs is an important advancement for future multi-omics studies and for better understanding the mechanisms of fermentation inhibition in lignocellulosic hydrolysates. The SH formulated in this work was instrumental for defining the most important inhibitors in the ACH. Major AFEX decomposition products are less inhibitory to yeast fermentation than the products of dilute acid or steam explosion pretreatments; thus, ACH is readily fermentable by yeast without any detoxification.

Methylnaltrexone for opioid-induced constipation in advanced illness.

BACKGROUND: Constipation is a distressing side effect of opioid treatment. As a quaternary amine, methylnaltrexone, a mu-opioid-receptor antagonist, has restricted ability to cross the blood-brain barrier. We investigated the safety and efficacy of subcutaneous methylnaltrexone for treating opioid-induced constipation in patients with advanced illness. METHODS: A total of 133 patients who had received opioids for 2 or more weeks and who had received stable doses of opioids and laxatives for 3 or more days without relief of opioid-induced constipation were randomly assigned to receive subcutaneous methylnaltrexone (at a dose of 0.15 mg per kilogram of body weight) or placebo every other day for 2 weeks. Coprimary outcomes were laxation (defecation) within 4 hours after the first dose of the study drug and laxation within 4 hours after two or more of the first four doses. Patients who completed this phase were eligible to enter a 3-month, open-label extension trial. RESULTS: In the methylnaltrexone group, 48% of patients had laxation within 4 hours after the first study dose, as compared with 15% in the placebo group, and 52% had laxation without the use of a rescue laxative within 4 hours after two or more of the first four doses, as compared with 8% in the placebo group (P<0.001 for both comparisons). The response rate remained consistent throughout the extension trial. The median time to laxation was significantly shorter in the methylnaltrexone group than in the placebo group. Evidence of withdrawal mediated by central nervous system opioid receptors or changes in pain scores was not observed. Abdominal pain and flatulence were the most common adverse events. CONCLUSIONS: Subcutaneous methylnaltrexone rapidly induced laxation in patients with advanced illness and opioid-induced constipation. Treatment did not appear to affect central analgesia or precipitate opioid withdrawal. (Clinical Trials.gov number, NCT00402038 [ClinicalTrials.gov].).