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A growing body of correlational research has revealed systematic relationships between various aspects of visuospatial processing and representational drawing ability. However, very few studies have sought to examine the longitudinal development of the relation between drawing and visuospatial ability. The current investigation explored change in drawing and visuospatial skill in art students taking a foundational drawing course (N = 42) in a longitudinal design. Measures of representational drawing skill, dispositional traits, and visuospatial skill were taken at three time points over the course of 5 months. The findings reveal improvements in representational drawing, mental rotation, disembedding figures, and attentional switching. However, individual differences in change over time on one task did not predict change in another, revealing implications for domain-specific and domain-general aspects of art and design expertise. [ABSTRACT FROM AUTHOR]

Fluoxetine is a safe antidepressant with remarkable anti‐inflammatory actions; therefore, we aimed to investigate its effects on immortalized (HaCaT) as well as primary human epidermal keratinocytes in a polyinosinic‐polycytidylic acid (p(I:C))‐induced inflammatory model. We found that a non‐cytotoxic concentration (MTT‐assay, CyQUANT‐assay) of fluoxetine significantly suppressed p(I:C)‐induced expression and release of several pro‐inflammatory cytokines (Q‐PCR, cytokine array, ELISA), and it decreased the release of the itch mediator endothelins (ELISA). These effects were not mediated by the inhibition of the NF‐κB or p38 MAPK pathways (western blot), or by the suppression of the p(I:C)‐induced elevation of mitochondrial ROS production (MitoSOX Red labeling). Instead, unbiased activity profiling revealed that they were most likely mediated via the inhibition of the phosphoinositide 3‐kinase (PI3K) pathway. Importantly, the PI3K‐inhibitor GDC0941 fully mimicked the effects of fluoxetine (Q‐PCR, ELISA). Although fluoxetine was able to occupy the binding site of GDC0941 (in silico molecular docking), and exerted direct inhibitory effect on PI3K (cell‐free PI3K activity assay), it exhibited much lower potency and efficacy as compared to GDC0941. Finally, RNA‐Seq analysis revealed that fluoxetine deeply influenced the transcriptional alterations induced by p(I:C)‐treatment, and exerted an overall anti‐inflammatory activity. Collectively, our findings demonstrate that fluoxetine exerts potent anti‐inflammatory effects, and suppresses the release of the endogenous itch mediator endothelins in human keratinocytes, most likely via interfering with the PI3K pathway. Thus, clinical studies are encouraged to explore whether the currently reported beneficial effects translate in vivo following its topical administration in inflammatory and pruritic dermatoses. [ABSTRACT FROM AUTHOR]

Objectives: The primary objective of this study was to compare the 12-month continuation rate for women who self-injected subcutaneous depot-medroxyprogesterone acetate (DMPA-SC) with that for women receiving intramuscular depot-medroxyprogesterone acetate (DMPA-IM) from a provider. This research contributes to the broader goal of identifying solutions to support women to use contraception for their full desired duration.Study Design: Participants were clients from 13 clinics in the Dakar and Thiés regions of Senegal who had decided to use injectable contraception prior to enrollment. They chose self-injection of DMPA-SC or provider administration of DMPA-IM. Self-injectors were trained and given three units of DMPA-SC. The provider-injected group received DMPA-IM and returned to the clinics for future injections. We interviewed participants at baseline and after the second, third and fourth injections (the equivalent of 12 months of contraceptive coverage). We employed Kaplan-Meier methods to estimate continuation probabilities, with a log-rank test to compare differences between groups. A multivariate Cox regression identified factors correlated with discontinuation.Results: The 12-month continuation rate for 650 women self-injecting DMPA-SC was 80.2%, while that for 649 women receiving DMPA-IM from a provider was 70.4% (p<.01). The difference in continuation between self-injectors and those receiving DMPA from a provider remained significant in a multivariate Cox regression model. The primary reason for discontinuation in both groups (44.7% self-injected; 44.5% provider-injected) was forgetting to reinject or reinjecting late. Fewer women reported side effects in the self-injection group than in the provider-administered group.Conclusions: The higher 12-month continuation rate for women self-injecting DMPA-SC relative to provider-administered DMPA-IM suggests that self-injection may help prevent pregnancy more consistently and continuously.Implications: Discontinuation of injectable contraception among women wishing to avoid pregnancy may increase unmet need in francophone West Africa. This study showed higher 12-month continuation rates for women who self-injected DMPA-SC, suggesting that this delivery method may improve injectable continuation. [ABSTRACT FROM AUTHOR]

A correction to the article "Clinical Evaluation of Safety and Immunogenicity of PADRE-Cytomegalovirus (CMV) and Tetanus-CMV Fusion Peptide Vaccines With or Without PF03512676 Adjuvant" that was published in the 2012 issue is presented.

Objective: To assess the cost-effectiveness of self-injected subcutaneous depot medroxyprogesterone acetate (DMPA-SC) compared to health-worker-administered intramuscular DMPA (DMPA-IM) in Uganda.Study Design: We developed a decision-tree model with a 12-month time horizon for a hypothetical cohort of approximately 1 million injectable contraceptive users in Uganda to estimate the incremental costs per pregnancy averted and per disability-adjusted life year (DALY) averted. The study design derived model inputs from DMPA-SC self-injection continuation and costing research studies and peer-reviewed literature. We calculated incremental cost-effectiveness ratios from societal and health system perspectives and conducted one-way and probabilistic sensitivity analyses to test the robustness of results.Results: Self-injected DMPA-SC could prevent 10,827 additional unintended pregnancies and 1620 maternal DALYs per year for this hypothetical cohort compared to DMPA-IM administered by facility-based health workers. Due to savings in women's time and travel costs, under a societal perspective, self-injection could save approximately US$1 million or $84,000 per year, depending on the self-injection training aid used. From a health system perspective, self-injection would avert more pregnancies but incur additional costs. A training approach using a one-page client instruction sheet would make self-injection cost-effective compared to DMPA-IM, with incremental costs per pregnancy averted of $15 and per maternal DALY averted of $98. Sensitivity analysis showed that the estimates were robust. The one-way and probabilistic sensitivity analyses showed that the costs of the first visit for self-injection (which include training costs) were an important variable impacting the cost-effectiveness estimates.Conclusions: Under a societal perspective, self-injected DMPA-SC averted more pregnancies and cost less compared to health-worker-administered DMPA-IM. Under a health system perspective, self-injected DMPA-SC can be cost-effective relative to DMPA-IM when a lower-cost visual aid for client training is used.Implications: Self-injection has economic benefits for women through savings in time and travel costs, and it averts additional pregnancies and maternal disability-adjusted life years compared to health-worker-administered injectable DMPA-IM. Implementing lower-cost approaches to client training can help ensure that self-injection is also cost-effective from a health system perspective. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the 12-month total direct costs (medical and nonmedical) of delivering subcutaneous depot medroxyprogesterone acetate (DMPA-SC) under three strategies - facility-based administration, community-based administration and self-injection - compared to the costs of delivering intramuscular DMPA (DMPA-IM) via facility- and community-based administration.Study Design: We conducted four cross-sectional microcosting studies in three countries from December 2015 to January 2017. We estimated direct medical costs (i.e., costs to health systems) using primary data collected from 95 health facilities on the resources used for injectable contraceptive service delivery. For self-injection, we included both costs of the actual research intervention and adjusted programmatic costs reflecting a lower-cost training aid. Direct nonmedical costs (i.e., client travel and time costs) came from client interviews conducted during injectable continuation studies. All costs were estimated for one couple year of protection. One-way sensitivity analyses identified the largest cost drivers.Results: Total costs were lowest for community-based distribution of DMPA-SC (US$7.69) and DMPA-IM ($7.71) in Uganda. Total costs for self-injection before adjustment of the training aid were $9.73 (Uganda) and $10.28 (Senegal). After adjustment, costs decreased to $7.83 (Uganda) and $8.38 (Senegal) and were lower than the costs of facility-based administration of DMPA-IM ($10.12 Uganda, $9.46 Senegal). Costs were highest for facility-based administration of DMPA-SC ($12.14) and DMPA-IM ($11.60) in Burkina Faso. Across all studies, direct nonmedical costs were lowest for self-injecting women.Conclusions: Community-based distribution and self-injection may be promising channels for reducing injectable contraception delivery costs. We observed no major differences in costs when administering DMPA-SC and DMPA-IM under the same strategy.Implications: Designing interventions to bring contraceptive service delivery closer to women may reduce barriers to contraceptive access. Community-based distribution of injectable contraception reduces direct costs of service delivery. Compared to facility-based health worker administration, self-injection brings economic benefits for women and health systems, especially with a lower-cost client training aid. [ABSTRACT FROM AUTHOR]

The article discusses a study that investigated the acceptability of contraceptive self-injection among adolescent childbearing women in Gulu,, Uganda. Findings showed that although self-injection of medroxyprogesterone depot was viewed favorably, some reservation were uncovered including fear of infertility, fear of needle, and potential of making mistake. Despite reservations, the study found that contraceptive self-injection has potential to increase contraceptive access in the area.

Objectives: Expanding contraceptive options through self-injection may improve access and confidentiality. There are few published studies on contraceptive self-injection in sub-Saharan Africa and none in West Africa, a region with high unmet need. This study was performed to assess feasibility of subcutaneous DMPA self-injection in Senegal; objectives were to (1) measure the proportion of participants who self-injected competently 3 months after training, (2) measure the proportion who self-injected on time (defined conservatively as within 7 days of reinjection date), and (3) assess acceptability of self-injection.Study Design: In this prospective cohort study, 378 women aged 18-49 years were trained to self-inject by study nurses. Three months later, women returned unprompted to the clinic to self-inject, and technique and visit timing were evaluated. Women continuing with a third self-injection were followed up at home after their next scheduled injection date. At each interaction, participants were interviewed to learn about their experience; additional questions during the final home visit focused on storage and disposal practices, and acceptability.Results: Among the 337 participants followed up 3 months post-training, 310 self-injected, and 87% did so competently. Factoring in women who declined to self-inject, electing to have the provider administer the injection instead, a total of 80% [95% confidence interval (CI)=75-84%] self-injected competently 3 months post-training, and 84% [95% CI=80-88%] reinjected on time, while 72% [95% CI=67-77%] were both on time and competent. The vast majority (93%) expressed a desire to continue.Conclusions: Self-injection is feasible and acceptable among most study participants in Senegal.Implications: These first research results on contraceptive self-injection in West Africa indicate initial feasibility and acceptability of the practice. Results underscore the importance of designing self-injection programs that empower and support women, including those with limited education. [ABSTRACT FROM AUTHOR]

Objectives: Evidence on contraceptive self-injection from the United States and similar settings is promising, and the practice may increase access. There are no published studies on the feasibility of contraceptive self-injection in sub-Saharan Africa to date. The purpose of this study was to assess feasibility of subcutaneous depot medroxyprogesterone acetate self-injection in Uganda, with specific objectives to (a) measure the proportion of participants who self-injected competently, (b) measure the proportion who self-injected on time 3 months after training (defined conservatively as within 7 days of their reinjection date) and (c) assess acceptability.Study Design: In this prospective cohort study, 380 18-45-year-old participants completed self-injection training by licensed study nurses, guided by a client instruction booklet, and practiced injection on prosthetics until achieving competence. Nurses supervised participants' self-injection and evaluated injection technique using an observation checklist. Those judged competent were given a Sayana® Press unit, instruction booklet and reinjection calendar for self-injection at home 3 months later. Participants completed an interview before and after self-injection. Nurses visited participants at home following reinjection dates; during the follow-up visit, participants demonstrated self-injection on a prosthetic, injection technique was reevaluated, and a postreinjection interview was completed.Results: Of 368 participants followed up 3 months posttraining, 88% [95% confidence interval (CI)=84-91] demonstrated injection competence, and 95% (95% CI=92-97) reinjected on time, while 87% (95% CI=84-90) were both on time and competent. Nearly all (98%) expressed a desire to continue.Conclusions: Self-injection is feasible and highly acceptable among most study participants in Uganda.Implications: The first research results on contraceptive self-injection in sub-Saharan Africa indicate initial feasibility and acceptability of the practice 3 months after women received one-on-one training and a highly visual training and memory aid. Results can inform self-injection programs which aim to increase women's autonomy and access to injectable contraception. [ABSTRACT FROM AUTHOR]

Attenuated poxvirus modified vaccinia Ankara (MVA) is a useful viral-based vaccine for clinical investigation, because of its excellent safety profile and property of inducing potent immune responses against recombinant (r) antigens. We developed Triplex by constructing an rMVA encoding 3 immunodominant cytomegalovirus (CMV) antigens, which stimulates a host antiviral response: UL83 (pp65), UL123 (IE1-exon4), and UL122 (IE2-exon5). We completed the first clinical evaluation of the Triplex vaccine in 24 healthy adults, with or without immunity to CMV and vaccinia virus (previous DryVax smallpox vaccination). Three escalating dose levels (DL) were administered IM in 8 subjects/DL, with an identical booster injection 28 days later and 1-year follow-up. Vaccinations at all DL were safe with no dose-limiting toxicities. No vaccine-related serious adverse events were documented. Local and systemic reactogenicity was transient and self-limiting. Robust, functional, and durable Triplex-driven expansions of CMV-specific T cells were detected by measuring T-cell surface levels of 4-1BB (CD137), binding to CMV-specific HLA multimers, and interferon-γ production. Marked and durable CMV-specific T-cell responses were also detected in Triplex-vaccinated CMV-seronegatives, and in DryVax-vaccinated subjects. Long-lived memory effector phenotype, associated with viral control during CMV primary infection, was predominantly found on the membrane of CMVspecific and functional T cells, whereas off-target vaccine responses activating memory T cells from the related herpesvirus Epstein-Barr virus remained undetectable. Combined safety and immunogenicity results of MVA in allogeneic hematopoietic stem cell transplant (HCT) recipients and Triplex in healthy adults motivated the initiation of a placebo-controlled multicenter trial of Triplex in HCT patients. [ABSTRACT FROM AUTHOR]

Winter deicers, though essential for maintaining safe pavement conditions in winter, increase chloride (Cl−) concentrations in receiving water bodies above recommended environmental guidelines. Zero-exfiltration or lined permeable pavement is an important technological innovation for controlling particulate-bound pollutants at the source. As stormwater does not infiltrate into the ground, soluble pollutants like Cl− are ultimately discharged into receiving water bodies. Our aim was to examine Cl− concentrations in effluents from three zero-exfiltration permeable pavement cells (Permeable Interlocking Concrete Pavement (PICP), Pervious Concrete (PC), Porous Asphalt (PA)) and compare them with runoff from a Conventional Asphalt (ASH) cell. The study conducted at a parking lot in St. Catharines, Ontario, Canada, from January 2016 to May 2017 observed that the permeable pavements provided only temporary attenuation of Cl− during winter but exhibited a quick release during spring melt. Cl− concentrations and loadings were different for each permeable pavement system in terms of timing and magnitude. Cl− concentration in ASH runoff frequently had very high spikes (21,780 mg/L); however, the median winter Cl− concentration in ASH runoff was lower than Cl− levels in the permeable pavements' effluents and later declined drastically after spring melt, but in few instances, was above the chronic water quality guideline (120 mg/L). The average event mean concentration (EMC) of Cl− was 1600 and 120 mg/L in the permeable pavements' effluents during salting and non-salting season, respectively. In one year, each permeable pavement system released approximately 67–81 kg of Cl− with significant differences being observed in Cl− loads between the 2016 and 2017 seasons. Therefore, a multi-year data collection and monitoring plan captured the variability in winter conditions. The study provided insights into the behaviour, retention and release of Cl− from traditional and permeable hardscape surfaces and possible avenues for Cl− attenuation, source control and aquatic habitat conservation. Fig. 1: Seasonal cumulative distribution functions of 15-min Cl− concentrations in stormwater from different permeable pavements (PICP, PC and PA). Non-Salting season 2017 only includes measurement from May 2017. The orange dashed line signifies the Canadian Water Quality Guidelines (CWQG) chronic limit for Cl− (120 mg/L), and the brown dashed signifies the CWQG acute limit for Cl− (640 mg/L). Since Cl− concentrations range by order of magnitude, different x-axis scales are used for readability for each season. [Display omitted] • Multi-year data collection study captured variability in winter conditions. • Permeable pavements provided temporary attenuation of chloride during winter. • Permeable pavements exhibited a quick release of chloride during spring melt. • Conventional asphalt runoff had very high spikes of chloride concentration. • The ecological implications of temporary attenuation of chloride were unclear. [ABSTRACT FROM AUTHOR]

Objectives: Study objectives were to explore nurses' perceptions of self-care, co-worker, and leader caring within healthcare work environments and assess reliability of 3 Watson Caritas Scores., Background: Assessing caring in an organization where Watson's Theory of Human Caring guides nursing practice offers insight into the professional practice environment., Method: This study reports quantitative data from mixed-methods descriptive, cross-sectional survey of 1307 RNs at a large healthcare system., Results: Mean scores were self = 5.46, co-worker = 5.39, and leader score = 5.53, and median scores were >5.6 (range, 1-7). All scales had a positive and significant correlation to likelihood to recommend the organization, with the largest being feeling cared for by leaders. Internal reliability of the 3 scales was ≥0.9., Conclusion: Nurse perceptions of caring may influence the organization's reputation. Assessing the perception of caring among nursing staff after the introduction and enculturation of this framework is needed. Results support psychometric value for 3 Watson Caritas Scores., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Hematopoietic cell transplantation (HCT) and chimeric antigen receptor (CAR)-T cell patients are immunocompromised, remain at high risk following SARS-CoV-2 infection, and are less likely than immunocompetent individuals to respond to vaccination. As part of the safety lead-in portion of a phase 2 clinical trial in patients post HCT/CAR-T for hematological malignancies (HM), we tested the immunogenicity of the synthetic modified vaccinia Ankara-based COVID-19 vaccine COH04S1 co-expressing spike (S) and nucleocapsid (N) antigens. Thirteen patients were vaccinated 3-12 months post HCT/CAR-T with two to four doses of COH04S1. SARS-CoV-2 antigen-specific humoral and cellular immune responses, including neutralizing antibodies to ancestral virus and variants of concern (VOC), were measured up to six months post vaccination and compared to immune responses in historical cohorts of naïve healthy volunteers (HV) vaccinated with COH04S1 and naïve healthcare workers (HCW) vaccinated with the FDA-approved mRNA vaccine Comirnaty ® (Pfizer, New York, NY, USA). After one or two COH04S1 vaccine doses, HCT/CAR-T recipients showed a significant increase in S- and N-specific binding antibody titers and neutralizing antibodies with potent activity against SARS-CoV-2 ancestral virus and VOC, including the highly immune evasive Omicron XBB.1.5 variant. Furthermore, vaccination with COH04S1 resulted in a significant increase in S- and N-specific T cells, predominantly CD4 + T lymphocytes. Elevated S- and N-specific immune responses continued to persist at six months post vaccination. Furthermore, both humoral and cellular immune responses in COH04S1-vaccinated HCT/CAR-T patients were superior or comparable to those measured in COH04S1-vaccinated HV or Comirnaty ® -vaccinated HCW. These results demonstrate robust stimulation of SARS-CoV-2 S- and N-specific immune responses including cross-reactive neutralizing antibodies by COH04S1 in HM patients post HCT/CAR-T, supporting further testing of COH04S1 in immunocompromised populations.

Self-care reproductive health innovations are increasingly valued as practices that enable women to manage their fertility with greater autonomy. While self-care, by definition, takes place beyond the clinic walls, many self-care practices nonetheless require initial or follow up visits to a health worker. Access to self-care hinges on the extent to which health care workers who serve as gatekeepers find the innovation appropriate and practical. Self-injection of subcutaneous depot medroxyprogesterone acetate (DMPA-SC) is being introduced and scaled in many countries. In late 2018, health workers in Uganda began offering self-injection of DMPA-SC in the public sector, and this study examines health workers' views on the acceptability and feasibility of training women to self-inject. We conducted in-person interviews with 120 health workers active in the self-injection program to better understand provider practices, program satisfaction, and their views on feasibility. A subset of 77 health workers participated in in-depth interviews. Quantitative data was analyzed using Stata (v14) software, and chi square and student t tests used to measure between group differences. Qualitative data was analyzed using Atlas.ti, employing an iterative coding process, to identify key themes that resonated. The majority of health workers were very satisfied with the self-injection program and reported it was moderately easy to integrate self-injection training into routine service delivery. They identified lack of time to train clients in the clinic setting, lack of materials among community health workers, and client fear of self-injection as key challenges. Community health workers were less likely to report time challenges and indicated higher levels of satisfaction and greater ease in offering self-injection services. The relatively high acceptability of the self-injection program among health workers is promising; however, strategies to overcome feasibility challenges, such as workload constraints that limit the ability to offer self-injection training, are needed to expand service delivery to more women interested in this new self-care innovation. As self-injection programs are introduced and scaled across settings, there is a need for evidence regarding how self-care innovations can be designed and implemented in ways that are practical for health workers, while optimizing women's successful adoption and use., Competing Interests: All authors were employed by PATH. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Morozoff, Cover, Namagembe, Nsangi, Komunyena Tumusiime, Stout and Kidwell Drake.)

Cell-mediated immunity may contribute to providing protection against SARS-CoV-2 and its variants of concern (VOC). We developed COH04S1, a synthetic multiantigen modified vaccinia Ankara (MVA)-based COVID-19 vaccine that stimulated potent spike (S) and nucleocapsid (N) antigen-specific humoral and cellular immunity in a phase 1 clinical trial in healthy adults. Here, we show that individuals vaccinated with COH04S1 or mRNA vaccine BNT162b2 maintain robust cross-reactive cellular immunity for six or more months post-vaccination. Although neutralizing antibodies induced in COH04S1- and BNT162b2-vaccinees showed reduced activity against Delta and Omicron variants compared to ancestral SARS-CoV-2, S-specific T cells elicited in both COH04S1- and BNT162b2-vaccinees and N-specific T cells elicited in COH04S1-vaccinees demonstrated potent and equivalent cross-reactivity against ancestral SARS-CoV-2 and the major VOC. These results suggest that vaccine-induced T cells to S and N antigens may constitute a critical second line of defense to provide long-term protection against SARS-CoV-2 VOC., Competing Interests: While unknown whether the publication of this report will aid in receiving grants and contracts, it is possible that this publication will be of benefit to the City of Hope (COH). COH had no role in the conceptualization, design, data collection, analysis, decision to publish, or preparation of the article. DJD and FW are co-inventors on a patent application covering the design and construction of the synthetic MVA platform (PCT/US2021/016,247). DJD, FW, and FC are co-inventors on a patent application covering the development of a COVID-19 vaccine (PCT/US2021/032,821). DJD is a consultant for GeoVax. All other authors declare no competing interests. GeoVax Labs Inc. has taken a worldwide exclusive license for COH04S1 under the name of GEO-CM04S1., (© 2022 The Author(s).)

Background: COH04S1, a synthetic attenuated modified vaccinia virus Ankara vector co-expressing SARS-CoV-2 spike and nucleocapsid antigens, was tested for safety and immunogenicity in healthy adults., Methods: This combined open-label and randomised, phase 1 trial was done at the City of Hope Comprehensive Cancer Center (Duarte, CA, USA). We included participants aged 18-54 years with a negative SARS-CoV-2 antibody and PCR test, normal haematology and chemistry panels, a normal electrocardiogram and troponin concentration, negative pregnancy test if female, body-mass index of 30 kg/m 2 or less, and no modified vaccinia virus Ankara or poxvirus vaccine in the past 12 months. In the open-label cohort, 1·0 × 10 7 plaque-forming units (PFU; low dose), 1·0 × 10 8 PFU (medium dose), and 2·5 × 10 8 PFU (high dose) of COH04S1 were administered by intramuscular injection on day 0 and 28 to sentinel participants using a queue-based statistical design to limit risk. In a randomised dose expansion cohort, additional participants were randomly assigned (3:3:1), using block size of seven, to receive two placebo vaccines (placebo group), one low-dose COH04S1 and one placebo vaccine (low-dose COH04S1 plus placebo group), or two low-dose COH04S1 vaccines (low-dose COH04S1 group). The primary outcome was safety and tolerability, with secondary objectives assessing vaccine-specific immunogenicity. The primary immunological outcome was a four times increase (seroconversion) from baseline in spike-specific or nucleocapsid-specific IgG titres within 28 days of the last injection, and seroconversion rates were compared with participants who received placebo using Fisher's exact test. Additional secondary outcomes included assessment of viral neutralisation and cellular responses. This trial is registered with ClinicalTrials.gov, NCT046339466., Findings: Between Dec 13, 2020, and May 24, 2021, 56 participants initiated vaccination. On day 0 and 28, 17 participants received low-dose COH04S1, eight received medium-dose COH04S1, nine received high-dose COH04S1, five received placebo, 13 received low-dose COH04S1 followed by placebo, and four discontinued early. Grade 3 fever was observed in one participant who received low-dose COH04S1 and placebo, and grade 2 anxiety or fatigue was seen in one participant who received medium-dose COH04S1. No severe adverse events were reported. Seroconversion was observed in all 34 participants for spike protein and 32 (94%) for nucleocapsid protein (p<0·0001 vs placebo for each comparison). Four times or more increase in SARS-CoV-2 neutralising antibodies within 56 days was measured in nine of 17 participants in the low-dose COH04S1 group, all eight participants in the medium-dose COH04S1 group, and eight of nine participants in the high-dose COH04S1 group (p=0·0035 combined dose levels vs placebo). Post-prime and post-boost four times increase in spike-specific or nucleocapsid-specific T cells secreting interferon-γ was measured in 48 (98%; 95% CI 89-100) of 49 participants who received at least one dose of COH04S1 and provided a sample for immunological analysis., Interpretation: COH04S1 was well tolerated and induced spike-specific and nucleocapsid-specific antibody and T-cell responses. Future evaluation of this COVID-19 vaccine candidate as a primary or boost vaccination is warranted., Funding: The Carol Moss Foundation and City of Hope Integrated Drug Development Venture programme., Competing Interests: DJD and FW are co-inventors on a patent application covering the design and construction of the synthetic modified vaccinia Ankara platform (PCT/US2021/016247). DJD, FW, and FC are co-inventors on a patent application covering the development of a COVID-19 vaccine (PCT/US2021/032821). FC, JAZ, PHF, RS, JD, BW, AMA, KFr, RAT, JKD, SD, AGP, DDN, PA, YC, HC, CLR, KT, YP, JM, AI, QZ, VK, DJ, KFa, TK, JN, MK, VHN, SOF, AW, FW, and DJD are employees of City of Hope National Medical Center (Duarte, CA, USA), which developed the vaccine and funded the trial. AS is a consultant for Gritstone, Flow Pharma, Merck, Epitogenesis, Gilead, and Avalia. La Jolla Institute for Immunology has filed for patent protection for various aspects of T-cell epitope and vaccine design work. All other authors declare no competing interests., (© 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

The recent detection of potent carcinogenic nitrosamine impurities in several human medicines has triggered product recalls and interrupted the supply of critical medications for hundreds of millions of patients, illuminating the need for increased testing of nitrosamines in pharmaceutical products. However, the development of analytical methods for nitrosamine detection is challenging due to high sensitivity requirements, complex matrices, and the large number and variety of samples requiring testing. Herein, we report an analytical method for the analysis of a common nitrosamine, N-nitrosodimethylamine (NDMA), in pharmaceutical products using full evaporation static headspace gas chromatography with nitrogen phosphorous detection (FE-SHSGC-NPD). This method is sensitive, specific, accurate, and precise and has the potential to serve as a universal method for testing all semi-volatile nitrosamines across different drug products. Through elimination of the detrimental headspace-liquid partition, a quantitation limit of 0.25 ppb is achieved for NDMA, a significant improvement upon traditional LC-MS methods. The extraction of nitrosamines directly from solid sample not only simplifies the sample preparation procedure but also enables the method to be used for different products as is or with minor modifications, as demonstrated by the analysis of NDMA in 10+ pharmaceutical products. The in situ nitrosation that is commonly observed in GC methods for nitrosamine analysis was completely inhibited by the addition of a small volume solvent containing pyrogallol, phosphoric acid, and isopropanol. Employing simple procedures and low-cost instrumentation, this method can be implemented in any analytical laboratory for routine nitrosamine analysis, ensuring patient safety and uninterrupted supply of critical medications. Graphical Abstract., (© 2022. Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, N.J., U.S.A.)

Bioretention cells can effectively infiltrate stormwater runoff and partly remove conventional water contaminants. A field tracer injection experiment in a conventionally designed bioretention cell was used to investigate the fate of benzotriazole, a model trace organic contaminant, during and between runoff events. Moderate (29%) benzotriazole load reductions were measured during the 6 h long injection experiment. The detection of 1-methyl benzotriazole, hydroxy benzotriazole, and methoxy benzotriazole provided in situ evidence of some rapid benzotriazole microbial transformation during the tracer test and more importantly between the events. The detection of benzotriazole alanine and benzotriazole acetyl alanine also showed fast benzotriazole phytotransformation to amino acid conjugates during the tracer test and suggests further transformation of phytotransformation products between events. These data provide conclusive full-scale evidence of benzotriazole microbial and phytotransformation in bioretention cells. Non-target chemical analysis revealed the presence of a diverse range of trace organic contaminants in urban runoff and exiting the bioretention cell, including pesticides and industrial, household, and pharmaceutical compounds. We have demonstrated the in situ potential of urban green infrastructure such as bioretention cells to eliminate polar trace organic contaminants from stormwater. However, targeted design and operation strategies, for example, hydraulic control and the use of soil amendments, should be incorporated for improved bioretention cell performance for such compounds.

Previous research has shown that drawing improves short-term mood in children when used to distract from rather than express negative thoughts and feelings. The current study sought to examine (a) how drawing might elevate mood in children ages 6-12 by examining the role played by absorption, enjoyment, and perceived competence as well as entering an imaginary world; and (b) whether children spontaneously use drawing to distract from a sad mood. Across three studies, children were asked to think of a disappointing event. After a sad mood induction, they drew for 5 min. Mood was measured before and after the mood induction and after drawing. Three main findings emerged. First, drawing to distract led to greater absorption and enjoyment than did drawing to express. Second, children's mood improved equally when drawing imaginary and real scenes showing that the key ingredient is that the content of the drawings be distracting in nature. Third, drawing improved mood even when children were given no instructions on the content of their drawings and children were more likely to use drawing as a way to distract themselves from a sad mood. These studies help to define the characteristics of drawing activities that foster mood improvement in children and highlight the important role of the arts in emotion regulation., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Drake.)

Synthetic peptides used as therapeutic medicines is continuing to grow as an area of focus within the pharmaceutical industry due to specificity and potency. As such, quality control areas need to continue to advance their capabilities to ensure that appropriate analyses are being performed, and that the data generated are both accurate and precise. One area which poses a significant challenge compared with traditional small molecule drug products is having a highly robust, low variability method of quantifying the assay of the active substance. As many peptide therapeutics are formulated as liquid drug products for injection and preparation procedures to make these samples amenable to traditional chromatographic analysis are inherently low variability (i.e., a simple dilution), potential sources of variance derived from the preparation of the analytical standards used to quantify the assay of the product must be investigated. Here, a fully nested ANOVA experimental design was utilized to examine this process. Such a design allowed for multiple variables to be interrogated as well as the potential interplay of such differences. It was determined that sonication of the standards contributed the most variance, while the balance used and scale on which the standard preparation procedure was performed also contributed significantly. Finally, different procedures for introducing the material into a coulometric Karl Fischer (KF) titration device to quantify the water content of the drug substance were compared and showed that indirect quantification by anhydrous methanol extraction is a significantly more variable method than using an Oven KF autosampler.

The microbiome of the female reproductive tract has implications for women's reproductive health. We examined the vaginal microbiome in two cohorts of women who experienced normal term births: a cross-sectionally sampled cohort of 613 pregnant and 1,969 non-pregnant women, focusing on 300 pregnant and 300 non-pregnant women of African, Hispanic or European ancestry case-matched for race, gestational age and household income; and a longitudinally sampled cohort of 90 pregnant women of African or non-African ancestry. In these women, the vaginal microbiome shifted during pregnancy toward Lactobacillus-dominated profiles at the expense of taxa often associated with vaginal dysbiosis. The shifts occurred early in pregnancy, followed predictable patterns, were associated with simplification of the metabolic capacity of the microbiome and were significant only in women of African or Hispanic ancestry. Both genomic and environmental factors are likely contributors to these trends, with socioeconomic status as a likely environmental influence.

The incidence of preterm birth exceeds 10% worldwide. There are significant disparities in the frequency of preterm birth among populations within countries, and women of African ancestry disproportionately bear the burden of risk in the United States. In the present study, we report a community resource that includes 'omics' data from approximately 12,000 samples as part of the integrative Human Microbiome Project. Longitudinal analyses of 16S ribosomal RNA, metagenomic, metatranscriptomic and cytokine profiles from 45 preterm and 90 term birth controls identified harbingers of preterm birth in this cohort of women predominantly of African ancestry. Women who delivered preterm exhibited significantly lower vaginal levels of Lactobacillus crispatus and higher levels of BVAB1, Sneathia amnii, TM7-H1, a group of Prevotella species and nine additional taxa. The first representative genomes of BVAB1 and TM7-H1 are described. Preterm-birth-associated taxa were correlated with proinflammatory cytokines in vaginal fluid. These findings highlight new opportunities for assessment of the risk of preterm birth.

Objectives: To evaluate the cost-effectiveness of self-injected subcutaneous depot medroxyprogesterone acetate (DMPA-SC) compared to health-worker-administered intramuscular DMPA (DMPA-IM) in Senegal and to assess how including practice or demonstration injections in client self-injection training affects estimates., Study Design: We developed a decision-tree model with a 12-month time horizon for a hypothetical cohort of 100,000 injectable contraceptive users in Senegal. We used the model to estimate incremental costs per disability-adjusted life year (DALY) averted. The analysis derived model inputs from DMPA-SC self-injection continuation and costing research studies and peer-reviewed literature. We evaluated the cost-effectiveness from societal and health system perspectives and conducted one-way and probabilistic sensitivity analyses to test the robustness of results., Results: Compared to health-worker-administered DMPA-IM, self-injected DMPA-SC could prevent 1402 additional unintended pregnancies and avert 204 maternal DALYs per year for this hypothetical cohort. From a societal perspective, self-injection costs less than health worker administration regardless of the training approach and is therefore dominant. From the health system perspective, self-injection is dominant compared to health worker administration if a one-page instruction sheet is used and one additional DMPA-SC unit is used for training and is cost-effective at $208 per DALY averted when two additional DMPA-SC units are used. Sensitivity analysis showed estimates were robust., Conclusions: Self-injected DMPA-SC averted more pregnancies and DALYs and cost less from the societal perspective compared to health-worker-administered DMPA-IM and hence is dominant. Using fewer DMPA-SC units for practice or demonstration improves cost-effectiveness of self-injection from the health system perspective., Implications: Evidence from Senegal shows that self-injection of DMPA-SC can be dominant or cost-effective from both health system and societal perspectives relative to DMPA-IM from health workers even if women practice injecting or health workers demonstrate with one or two DMPA-SC units. Evidence on whether practice or demonstration is required for client training would be useful., (© 2019 The Authors.)

Municipal wastewater contains bacteria, viruses, and other pathogens that adversely affect the environment, human health, and economic activity. One way to mitigate these effects is a final disinfection step using ultraviolet light (UVL). The advantages of UVL disinfection, when compared to the more traditional chlorine, include no chlorinated by-products, no chemical residual, and relatively compact size. The design of most UV reactors is complex. It involves lamp selection, power supply design, optics, and hydraulics. In general, medium pressure lamps are more compact, powerful, and emit over a wider range of light than the more traditional low pressure lamps. Low pressure lamps, however, may be electrically more efficient. In UV disinfection, the fraction of surviving organisms (e.g. E. coli) will decrease exponentially with increasing UV dose. However, the level of disinfection that can be achieved is often limited by particle-associated organisms. Efforts to remove or reduce the effects of wastewater particles will often improve UV disinfection effectiveness. Regrowth, photoreactivation, or dark repair after UV exposure are sometimes cited as disadvantages of UV disinfection. Research is continuing in this area, however there is little evidence that human pathogens can photoreactivate in environmental conditions, at doses used in wastewater treatment. The UV disinfection of combined sewer overflows, a form of wet weather pollution, is challenging and remains largely at the research phase. Pre-treatment of combined sewer overflows (CSOs) with a cationic polymer to induce fast settling, and a low dose of alum to increase UV transmittance, has shown promise at the bench scale.

We examined two ways in which drawing may function to elevate mood in children-venting (expressing negative feelings) and distraction (expressing something unrelated to the negative feelings). We examined the effectiveness of drawing as an emotion regulator when drawing is used to vent versus distract (Study 1) and tested whether the effects found are specific to the activity of creating one's own drawing or generalisable to a drawing activity in which children had to copy another's drawing (Study 2). To induce a negative mood, we asked children to think of a disappointing event. Mood was assessed before and after the assigned activity. In both studies, mood improved significantly more in the distract than in the vent or copy condition. Study 1 demonstrates that drawing improves mood in children via distraction and not via venting. Study 2 demonstrates that this effect is specific to a drawing task in which an image is freely constructed. When a copying task is used, the effect disappears.

Objective: To assess private-sector stakeholders' and donors' perceptions of a total market approach (TMA) to family planning in Nicaragua in the context of decreased funding; to build evidence for potential strategies and mechanisms for TMA implementation (including public-private partnerships (PPPs)); and to identify information gaps and future priorities for related research and advocacy., Methods: A descriptive exploratory study was conducted in various locations in Nicaragua from March to April 2010. A total of 24 key private-sector stakeholders and donors were interviewed and their responses analyzed using two questionnaires and a stakeholder analysis tool (PolicyMakerTM software)., Results: All survey participants supported a TMA, and public-private collaboration, in family planning in Nicaragua. Based on the survey responses, opportunities for further developing PPPs for family planning include building on and expanding existing governmental frameworks, such as Nicaragua's current coordination mechanism for contraceptive security. Obstacles include the lack of ongoing government engagement with the commercial (for-profit) sector and confusion about regulations for its involvement in family planning. Strategies for strengthening existing PPPs include establishing a coordination mechanism specifically for the commercial sector and collecting and disseminating evidence supporting public-private collaboration in family planning., Conclusions: There was no formal or absolute opposition to a TMA or PPPs in family planning in Nicaragua among a group of diverse nongovernmental stakeholders and donors. This type of study can help identify strategies to mobilize existing and potential advocates in achieving articulated policy goals, including diversification of funding sources for family planning to achieve contraceptive security.

Evidence-informed public health refers to the process of applying proven interventions within the context of community preferences in order to achieve positive health impacts. A key role for nongovernmental organizations (NGOs) in evidence-informed public health is to use and expand on research to help shape appropriate interventions for diverse communities. This article suggests that NGOs are particularly well positioned for this role for a number of reasons, including their geographic reach, their engagement with diverse stakeholders, and their extragovernmental position, which enables them to develop and advocate for innovative, scientifically sound solutions to long-standing health challenges. Three case studies are presented that highlight how NGOs can harness these advantages to shape evidence-informed policies and programs to improve women's health: PATH's multicountry HPV Vaccines project, the International Consortium for Emergency Contraception, and a collaborative effort to combat maternal mortality in Mali.

Mitochondria under oxidative stress are thought to play a key role in various neurodegenerative disorders by directing neurons to cell death. Protection by antioxidants against oxidative stress to mitochondria may prove to be beneficial in delaying onset or progression of these diseases. We have investigated the ability of gamma-glutamylcysteine ethyl ester (GCEE) to upregulate mitochondrial glutathione (GSH) in vivo or in vitro and protect against subsequent in vitro peroxynitrite (ONOO-) damage. Mitochondria pretreated in vitro with GCEE were protected against oxidative damage induced by peroxynitrite, as assessed by mitochondrial swelling, changes in mitochondrial membrane potential, 3-nitrotyrosine formation, protein carbonyl formation, and cytochrome c release. Loss of mitochondrial function in neuronal cell cultures by the oxidants 2,2,'Azobis(2-amidino-propane)dihydrochloride (AAPH) and ONOO- was ameliorated by treatment with GCEE. In vivo studies showed that mitochondria isolated from animals injected intraperitoneally with GCEE were protected partially against oxidative modifications induced by ONOO-. Taken together, these results suggest that GCEE may be effective in increasing mitochondrial GSH and may be prove to have therapeutic relevance in neurodegenerative disorders associated with oxidative stress and mitochondrial dysfunction., (Copyright 2003 Wiley-Liss, Inc.)

Elevation of glutathione (GSH) has been recognized as an important method for modulating levels of reactive oxygen species (ROS) in the brain. We investigated the antioxidant properties of gamma-glu-cys-ethyl ester (GCEE) in vitro and its ability to increase GSH levels upon in vivo i.p. injection. GCEE displays antioxidant activity similar to GSH as assessed by various in vitro indices such as hydroxyl radical scavenging, dichlorofluorescein fluorescence (DCF), protein specific spin labeling, glutamine synthetase (GS) activity, and protein carbonyls. Intraperitoneal injection of GCEE to gerbils resulted in a 41% increase in brain total GSH levels in vivo as determined by the DTNB-GSH reductase recycling method. Gerbils injected with buthionine sulfoximine (BSO), an inhibitor of gamma-glutamylcysteine synthetase, had 40% less total brain glutathione. Gerbils injected with BSO followed by a GCEE injection had GSH levels similar to vehicle-injected controls, suggesting that GCEE upregulates GSH biosynthesis by providing gamma-glutamylcysteine and not cysteine. Cortical synaptosomes from GCEE-injected animals were less susceptible to peroxynitrite-induced oxidative damage as assessed by DCF fluorescence, protein-specific spin labeling, and GS activity. These experiments suggest that GCEE is effective in increasing brain GSH levels and may potentially play an important therapeutic role in attenuating oxidative stress in neurodegenerative diseases associated with oxidative stress such as Alzheimer disease., (Copyright 2002 Wiley-Liss, Inc.)