Toxoplasma gondii infection supports the infiltration of T cells into brain tumors.

Few T cells infiltrate into primary brain tumors, fundamentally hampering the effectiveness of immunotherapy. We hypothesized that Toxoplasma gondii, a microorganism that naturally elicits a Th1 response in the brain, can promote T cell infiltration into brain tumors despite their immune suppressive microenvironment. Using a mouse genetic model for medulloblastoma, we found that T. gondii infection induced the infiltration of activatable T cells into the tumor mass and led to myeloid cell reprogramming toward a T cell-supportive state, without causing severe health issues in mice. The study provides a concrete foundation for future studies to take advantage of the immune modulatory capacity of T. gondii to facilitate brain tumor immunotherapy.

Resilience partially mediates the association between perceived social isolation and life satisfaction in people with systemic sclerosis.

Objectives: Systemic sclerosis (SSc) negatively affects quality of life, yet the factors influencing life satisfaction, a key aspect of well-being, remain unclear in this population. Social isolation is common in SSc, potentially linked to decreased life satisfaction, but the underlying mechanisms are unexplored. Resilience, a modifiable psychological resource, may act as a mediator in this relationship among people with SSc. This study aimed to examine the relationship between perceived social isolation and life satisfaction and to investigate whether resilience mediates this relationship. Methods: The Patient-Reported Outcomes Measurement Information System Social Isolation Short Form, the Connor-Davidson Resilience Scale, and the Satisfaction with Life Scale were used to assess perceived social isolation, resilience, and life satisfaction. Linear regressions were conducted using the PROCESS macro for SPSS. Results: Among 163 individuals with SSc who provided complete data at baseline (mean age = 54.7 ± 11.9 years), 47% had diffuse cutaneous SSc, and 57% had an early disease duration. Perceived social isolation was negatively associated with life satisfaction. Resilience partially mediated the association between perceived social isolation and life satisfaction in people with SSc. Conclusions: Findings revealed a significant association between perceived social isolation and life satisfaction and the mediating role of resilience in this association among people with SSc. Results suggest resilience may act as a protective mediator, counteracting the negative influence of perceived social isolation on life satisfaction. Findings support the promotion of social connection and resilience to enhance life satisfaction in people with SSc. Clinical Trials Registration #: NCT04908943.

Integration mapping of cardiac fibroblast single-cell transcriptomes elucidates cellular principles of fibrosis in diverse pathologies.

Single-cell technology has allowed researchers to probe tissue complexity and dynamics at unprecedented depth in health and disease. However, the generation of high-dimensionality single-cell atlases and virtual three-dimensional tissues requires integrated reference maps that harmonize disparate experimental designs, analytical pipelines, and taxonomies. Here, we present a comprehensive single-cell transcriptome integration map of cardiac fibrosis, which underpins pathophysiology in most cardiovascular diseases. Our findings reveal similarity between cardiac fibroblast (CF) identities and dynamics in ischemic versus pressure overload models of cardiomyopathy. We also describe timelines for commitment of activated CFs to proliferation and myofibrogenesis, profibrotic and antifibrotic polarization of myofibroblasts and matrifibrocytes, and CF conservation across mouse and human healthy and diseased hearts. These insights have the potential to inform knowledge-based therapies.

Pembrolizumab-induced Stevens-Johnson syndrome/Toxic Epidermal Necrolysis in a Vietnamese patient with nonsmall-cell lung cancer.

Chemoimmunotherapy is an effective therapy for an individual with nonsmall-cell lung cancer (NSCLC) without anaplastic lymphoma kinase or epidermal growth factor receptor mutations. However, it can also be related to adverse cutaneous reactions such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) with high morbidities and mortality rates. We present a case of a 65-year-old male with NSCLC who underwent first-line chemotherapy with paclitaxel, carboplatin, and pembrolizumab, which was later followed by a second cycle of the same therapies. The patient developed a fever and rash 12 days after the second cycle. Pembrolizumab was strongly suspected as the culprit medication because cutaneous reactions to this drug have been frequently reported and threw other medications used as less likely candidates. This is the first case reported in Vietnam of SJS/TEN related to pembrolizumab and contributes to our knowledge of severe skin reactions associated with immune checkpoint inhibitors.

Hippo-YAP/TAZ signalling coordinates adipose plasticity and energy balance by uncoupling leptin expression from fat mass.

Adipose tissues serve as an energy reservoir and endocrine organ, yet the mechanisms that coordinate these functions remain elusive. Here, we show that the transcriptional coregulators, YAP and TAZ, uncouple fat mass from leptin levels and regulate adipocyte plasticity to maintain metabolic homeostasis. Activating YAP/TAZ signalling in adipocytes by deletion of the upstream regulators Lats1 and Lats2 results in a profound reduction in fat mass by converting mature adipocytes into delipidated progenitor-like cells, but does not cause lipodystrophy-related metabolic dysfunction, due to a paradoxical increase in circulating leptin levels. Mechanistically, we demonstrate that YAP/TAZ-TEAD signalling upregulates leptin expression by directly binding to an upstream enhancer site of the leptin gene. We further show that YAP/TAZ activity is associated with, and functionally required for, leptin regulation during fasting and refeeding. These results suggest that adipocyte Hippo-YAP/TAZ signalling constitutes a nexus for coordinating adipose tissue lipid storage capacity and systemic energy balance through the regulation of adipocyte plasticity and leptin gene transcription.

Impact of a resilience-building energy management intervention for people with systemic sclerosis: a mixed methods study.

Objectives: People with SSc often experience fatigue, which significantly affects daily life functioning and quality of life. We aimed to explore participants' experiences of a peer health-coached resilience-building energy management to enhance well-being (RENEW) intervention on symptoms and well-being and to use mixed methods to compare how SSc duration influenced the experiences of participants who had clinically significant fatigue improvement vs those who did not. Methods: Semi-structured interviews were conducted with 21 participants from the parent clinical trial randomized to the RENEW intervention. Data were analysed using the rigorous and accelerated data reduction technique combined with thematic content analysis. A mixed methods approach used a joint display to identify themes related to the impact of SSc duration on fatigue improvement status. Participants were categorized into short/improvement, short/limited improvement, long/improvement, and long/limited improvement. Results: Our team generated four themes: participant and peer health-coach relationship, physical and psychological well-being improvement, need for a tailored approach and easy program access through technology. Mixed methods analysis revealed that, regardless of SSc duration, participants with improved fatigue reported increasing self-awareness of SSc-related symptoms and learning coping strategies to manage fatigue. Participants in the short/improvement group reported preferences for slower pacing of the program and pairing with a coach with similar symptom severity. Participants in the long/limited improvement group sought SSc-specific symptom management information. Conclusion: Incorporating peer health coaches and technology is beneficial for self-management interventions for people with SSc. Future tailoring of RENEW based on SSc duration and symptom severity is needed. Clinical trial registration number: clinicatrials.gov, NCT04908943.

Acute Kidney Injury After Percutaneous Coronary Intervention Guided by Intravascular Ultrasound.

Purpose We investigated the impact of intravascular ultrasound guidance on reducing the incidence of contrast-induced acute kidney injury (CI-AKI) in patients undergoing percutaneous coronary intervention (PCI). Methods Ninety-nine patients were enrolled in this prospective cohort who were not randomly assigned to angiography-guided percutaneous coronary intervention or intravascular ultrasound-guided percutaneous coronary intervention. The patients were hospitalized at the Vietnam National Heart Institute - Bach Mai Hospital between 2019 and 2020. Acute kidney injury incidence during hospitalization was the primary endpoint. Results A total of 99 patients were divided into two groups: the intravascular ultrasound-guided group (33 participants) and the angiography-guided group (66 participants). The mean ± SD contrast volume of each group was 95.2 ± 37.1 mL and 133.0 ± 36.0 mL for the ultrasound-guided and angiography-guided groups, with P < 0.0001. Intravascular imaging-guided percutaneous coronary intervention (IVUS-guided PCI) was associated with reduced acute kidney injury incidence during hospitalization: 0.0% vs. 12.12% and P = 0.049. Conclusions Intravascular ultrasound is a safe imaging tool that guides percutaneous coronary intervention and significantly reduces the rate of acute kidney injury compared to angiography alone. Patients who have a high chance of experiencing acute kidney injury benefit from using intravascular ultrasound.

Peer-Led Symptom Management Intervention to Enhance Resilience in People With Systemic Sclerosis: Mediation Analysis From a Randomized Clinical Trial.

OBJECTIVE: Facilitated self-management interventions have the potential to enhance resilience and well-being. We examined whether resilience is a mediator of improving physical and psychological symptoms for people with systemic sclerosis (SSc) who participated in a 12-week online peer-led symptom management intervention. METHODS: We conducted a secondary data analysis from a randomized control trial comparing a peer health-coached intervention to a waitlist control. Participants completed the Connor-Davidson Resilience Scale, the Functional Assessment of Chronic Illness Therapy-Fatigue scale, and the Patient Reported Outcomes Measurement Information System measures of pain interference and depressive symptoms at the baseline and at weeks 6 and 12. Linear mixed effect regression models were used to assess the effect of intervention on changes in resilience. Causal mediation analyses were conducted to examine whether changes in resilience at week 12 mediated intervention effects on changes in fatigue, pain interference, and depressive symptoms at week 12. RESULTS: One hundred and seventy-three eligible participants were enrolled. Participants in the intervention group reported improvements in resilience (P < 0.001). These changes in resilience mediated the intervention effects on fatigue with indirect effect of -1.41 (95% confidence interval [CI] -2.41 to -0.41), pain interference of -0.86 (95% CI -1.65 to -0.08), and depressive symptoms of -1.99 (95% CI -3.16 to -0.81). CONCLUSION: For participants in the intervention who had positive improvements in their physical and psychological symptoms, increased resilience was a mechanism for these improvements. These findings support the importance of addressing resilience to improve symptoms in similar SSc interventions.

Creating a flow restrictor in ductal stenting: a novel technique.

Ductal stenting has transformed the care of neonates with ductal-dependent critical CHD, especially in low-income countries. In small infants, a 3.5- or 4-mm stent may lead to too much pulmonary blood flow resulting in pulmonary oedema. We herein presented a novel technique to restrict ductal stent flow in a premature neonate with pulmonary atresia and intact ventricular septum following radiofrequency perforation of the pulmonary valve.

Seroprevalence of SARS-CoV-2 in 10 Regional Capitals of Cameroon, October-December 2020.

BACKGROUND: Cameroon was among the most affected African countries during the first wave of the COVID-19 pandemic; however, the true prevalence of SARS-CoV-2 remains unknown. METHODS: From October to December 2020, we conducted a cross-sectional, age-stratified SARS-CoV-2 seroepidemiological survey at 30 purposively selected community-based sites across Cameroon's 10 regional capitals, sampling 10,000 individuals aged 5 years or older. We employed a parallel SARS-CoV-2 antibody testing algorithm (WANTAI ELISA and Abbott Architect) to improve both the positive predictive value and negative predictive value of seroprevalence. RESULTS: The overall weighted and adjusted seroprevalence of SARS-CoV-2 antibodies across the 10 urban capitals of Cameroon was 10.5% (95% CI: 9.1%-12.0%) among participants aged ≥5 years. Of the 9332 participants, 730 males (13.1%, 95% CI: 11.5%-14.9%) had SARS-CoV-2 antibodies compared to 293 females (8.0%, 95% CI: 6.8%-9.3%). Among those who reported a comorbidity at the time of testing, 15.8% (95% CI: 12.8%-19.4%) were seropositive. We estimated that over 2 million SARS-CoV-2 infections occurred in the 10 regional capitals of Cameroon between October and December 2020, compared to 21,160 cases officially reported at that time translating to one laboratory-confirmed case being reported for every 110 SARS-CoV-2 infections across the 10 urban capitals. CONCLUSION: This study's findings point to extensive and under-reported circulation of SARS-CoV-2 in Cameroon-an almost 100-fold more cases compared to the number of cases reported to the World Health Organization. This finding highlights the importance of conducting serosurveys, especially in settings where access to testing may be limited and to repeat such surveys as part of pandemic tracking.

Brief Report: Self-Reported HIV-Positive Status but Subsequent HIV-Negative Test Results in Population-Based HIV Impact Assessment Survey Participants-11 Sub-Saharan African Countries, 2015-2018.

BACKGROUND: HIV testing is a critical step to accessing antiretroviral therapy (ART) because early diagnosis can facilitate earlier initiation of ART. This study presents aggregated data of individuals who self-reported being HIV-positive but subsequently tested HIV-negative during nationally representative Population-Based HIV Impact Assessment surveys conducted in 11 countries from 2015 to 2018. METHOD: Survey participants aged 15 years or older were interviewed by trained personnel using a standard questionnaire to determine HIV testing history and self-reported HIV status. Home-based HIV testing and counseling using rapid diagnostic tests with return of results were performed by survey staff according to the respective national HIV testing services algorithms on venous blood samples. Laboratory-based confirmatory HIV testing for all participants identified as HIV-positives and self-reported positives, irrespective of HIV testing results, was conducted and included Geenius HIV-1/2 and DNA polymerase chain reaction if Geenius was negative or indeterminate. RESULTS: Of the 16,630 participants who self-reported as HIV-positive, 16,432 (98.6%) were confirmed as HIV-positive and 198 (1.4%) were HIV-negative by subsequent laboratory-based testing. Participants who self-reported as HIV-positive but tested HIV-negative were significantly younger than 30 years, less likely to have received ART, and less likely to have received a CD4 test compared with participants who self-reported as HIV-positive with laboratory-confirmed infection. CONCLUSIONS: A small proportion of self-reported HIV-positive individuals could not be confirmed as positive, which could be due to initial misdiagnosis, deliberate wrong self-report, or misunderstanding of the questionnaire. As universal ART access is expanding, it is increasingly important to ensure quality of HIV testing and confirmation of HIV diagnosis before ART initiation.

Diabetic Kidney Disease in Post-Kidney Transplant Patients.

Post-transplant diabetes mellitus (PTDM) is a common occurrence in post-kidney transplantation and is associated with greater mortality, allograft failure, and increased risk of infections. The primary goal in the management of PTDM is to achieve glycemic control to minimize the risk of complications while balancing the need for immunosuppression to maintain the health of the transplanted kidney. This review summarizes the effects of maintenance immunosuppression and therapeutic options among kidney transplant recipients. Patients with PTDM are at increased risk of diabetic kidney disease development; therefore, in this review, we focus on evidence supporting the use of novel antidiabetic agents and discuss their benefits and potential side effects in detail.

Effects of a Resilience-Building Energy Management Program on Fatigue and Other Symptoms in Systemic Sclerosis: A Randomized Controlled Trial.

OBJECTIVE: Supported self-management interventions for individuals with systemic sclerosis (SSc) are needed. We examined the effects of a 12-week resilience-building energy management program (called RENEW) for fatigue and other patient-reported outcomes. METHODS: Participants, who had physician-diagnosed SSc, moderate to severe fatigue, and were ≥18 years old, were randomly assigned to RENEW or waitlist control in a 2:1 ratio. The RENEW intervention included an educational website/application plus nine virtual peer-led health coaching sessions. The primary outcome was change in the Functional Assessment of Chronic Illness Therapy-Fatigue scale. Secondary outcomes were change in Patient Reported Outcomes Measurement Information System measures of pain interference and depressive symptoms and Connor-Davidson Resilience Scale. Outcomes were assessed at baseline, 6 weeks, and 12 weeks. Multiple imputation was conducted; linear mixed models were used to assess group differences. A three-way interaction with group, time, and SSc duration was examined in each model. RESULTS: Among 173 participants (mean ± SD age 54.5 ± 11.7 years; 93% female, 85% White), 47% had diffuse cutaneous SSc; 57% were ≤5 years from diagnosis. At 12 weeks, compared to controls, RENEW participants had a clinically meaningful fatigue improvement (ß = -4.7; 95% confidence interval -6.7 to -2.7; P < 0.001) and improvement in all secondary outcomes. Among RENEW participants, individuals with shorter disease duration had greater improvements in fatigue at 12 weeks. CONCLUSION: An mHealth supported self-management intervention improved fatigue and other outcomes, particularly in newly diagnosed patients. This program may be broadly scalable for SSc symptom management.

Non-pharmacological rehabilitation interventions for individuals with antiphospholipid syndrome: A scoping review.

OBJECTIVE: The objective of this study was to explore what non-pharmacological interventions have been examined for individuals with antiphospholipid syndrome (APS). METHODS: We conducted a systematic literature search of the databases PubMed, Embase, Scopus, Web of Science, CINAHL, and ClinicalTrials.gov from 1983-Feb. 2023. Our scoping review included studies that examined non-pharmacological interventions for individuals with APS using patient-reported outcome measures. We excluded studies that reported physiological outcomes only. RESULTS: The review yielded one case study on the safety and efficacy of an exercise program for a 15-year-old male with secondary APS using physiological and patient-reported outcome measures. Despite the lack of evidence of non-pharmacological interventions for individuals with APS, one excluded study reported that individuals with APS want guidance about physical activity and exercise. We also found several types of potentially relevant non-pharmacological interventions for individuals with lupus, a disease that often co-occurs with APS. CONCLUSIONS: Non-pharmacological interventions may offer a solution for addressing some non-thrombotic or non-obstetric APS symptoms, such as neurological, physical, and cognitive symptoms that are not well-controlled by anticoagulation. Due to the unique risks associated with APS, research is needed to determine the safety and efficacy of non-pharmacological interventions, particularly those involving exercise. Adopting a comprehensive, multidisciplinary approach to managing patients with APS and involving rehabilitation professionals, who are experts in the design and delivery of non-pharmacological interventions, may provide a foundation for developing and testing novel interventions that improve health outcomes while also fulfilling unmet needs reported by patients.

Risk Factors for Recent HIV Infections among Adults in 14 Countries in Africa Identified by Population-Based HIV Impact Assessment Surveys, 2015-2019.

Identifying persons who have newly acquired HIV infections is critical for characterizing the HIV epidemic direction. We analyzed pooled data from nationally representative Population-Based HIV Impact Assessment surveys conducted across 14 countries in Africa for recent infection risk factors. We included adults 15-49 years of age who had sex during the previous year and used a recent infection testing algorithm to distinguish recent from long-term infections. We collected risk factor information via participant interviews and assessed correlates of recent infection using multinomial logistic regression, incorporating each survey's complex sampling design. Compared with HIV-negative persons, persons with higher odds of recent HIV infection were women, were divorced/separated/widowed, had multiple recent sex partners, had a recent HIV-positive sex partner or one with unknown status, and lived in communities with higher HIV viremia prevalence. Prevention programs focusing on persons at higher risk for HIV and their sexual partners will contribute to reducing HIV incidence.

Comparing Catastrophic Costs: Active vs. Passive Tuberculosis Case Finding in Urban Vietnam.

Active case finding (ACF) is a strategy that aims to identify people with tuberculosis (TB) earlier in their disease. This outreach approach may lead to a reduction in catastrophic cost incurrence (costs exceeding 20% of annual household income), a main target of WHO's End TB Strategy. Our study assessed the socio-economic impact of ACF by comparing patient costs in actively and passively detected people with TB. Longitudinal patient cost surveys were prospectively fielded for people with drug-sensitive pulmonary TB, with 105 detected through ACF and 107 passively detected. Data were collected in four Vietnamese cities between October 2020 and March 2022. ACF reduced pre-treatment (USD 10 vs. 101, p < 0.001) and treatment costs (USD 888 vs. 1213, p < 0.001) in TB-affected individuals. Furthermore, it reduced the occurrence of job loss (15.2% vs. 35.5%, p = 0.001) and use of coping strategies (28.6% vs. 45.7%, p = 0.004). However, catastrophic cost incurrence was high at 52.8% and did not differ between cohorts. ACF did not significantly decrease indirect costs, the largest contributor to catastrophic costs. ACF reduces costs but cannot sufficiently reduce the risk of catastrophic costs. As income loss is the largest driver of costs during TB treatment, social protection schemes need to be expanded.

Purpurascenines A-C, Azepino-Indole Alkaloids from Cortinarius purpurascens: Isolation, Biosynthesis, and Activity Studies on the 5-HT2A Receptor.

Three previously undescribed azepino-indole alkaloids, named purpurascenines A-C (1-3), together with the new-to-nature 7-hydroxytryptophan (4) as well as two known compounds, adenosine (5) and riboflavin (6), were isolated from fruiting bodies of Cortinarius purpurascens Fr. (Cortinariaceae). The structures of 1-3 were elucidated based on spectroscopic analyses and ECD calculations. Furthermore, the biosynthesis of purpurascenine A (1) was investigated by in vivo experiments using 13C-labeled sodium pyruvate, alanine, and sodium acetate incubated with fruiting bodies of C. purpurascens. The incorporation of 13C into 1 was analyzed using 1D NMR and HRESIMS methods. With [3-13C]-pyruvate, a dramatic enrichment of 13C was observed, and hence a biosynthetic route via a direct Pictet-Spengler reaction between α-keto acids and 7-hydroxytryptophan (4) is suggested for the biosynthesis of purpurascenines A-C (1-3). Compound 1 exhibits no antiproliferative or cytotoxic effects against human prostate (PC-3), colorectal (HCT-116), and breast (MCF-7) cancer cells. An in silico docking study confirmed the hypothesis that purpurascenine A (1) could bind to the 5-HT2A serotonin receptor's active site. A new functional 5-HT2A receptor activation assay showed no functional agonistic but some antagonistic effects of 1 against the 5-HT-dependent 5-HT2A activation and likely antagonistic effects on putative constitutive activity of the 5-HT2A receptor.

Factors associated with life satisfaction in systemic sclerosis: Examining the moderating roles of social support and spiritual well-being.

Objectives: Systemic sclerosis often has a significant impact on an individual's quality of life. Life satisfaction is a subjective expression of well-being and a key component of quality of life. We examined the associations between functional limitations, social support, and spiritual well-being with life satisfaction and investigated the moderating roles of social support and spiritual well-being on the relationship between functional limitations and life satisfaction in people with systemic sclerosis. Methods: Data were drawn from the baseline University of California Los Angeles Scleroderma Quality of Life Study. Participants completed questionnaires that included demographics, depressive symptoms, functional limitations, social support, and spiritual well-being. The Satisfaction with Life Scale was used to evaluate overall life satisfaction. Data were analyzed using a hierarchical linear regression. Results: Of 206 participants (84% female, 74% White, 52% limited cutaneous subtype, 51% early disease), 38% reported being dissatisfied with their lives. Functional limitations (ß = -0.19, p = 0.006), social support (ß = 0.18, p = 0.006), and spiritual well-being (ß = 0.40, p < 0.001) were associated with life satisfaction, with spiritual well-being emerging as the strongest statistical contributor. However, social support and spiritual well-being did not significantly moderate the relationship between functional limitations and life satisfaction (p = 0.882 and p = 0.339, respectively). Conclusion: Spiritual well-being is particularly important in understanding life satisfaction in people with systemic sclerosis. Future longitudinal research is needed to assess and examine spiritual well-being and its impact on life satisfaction in a larger and more diverse systemic sclerosis sample.