Exploring the Role of Th10 Cells and IL-10 in Systemic Lupus Erythematosus.

INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by autoantibody production and immune complex deposition in various organs. The pathogenesis of SLE is multifactorial, involving genetic, hormonal, environmental, and immune factors. Interleukin-10 (IL-10) is a pleiotropic cytokine produced by various immune cells and has conflicting roles in inflammation. MATERIALS AND METHODS: This is a cross-sectional study involving 56 SLE patients and 30 healthy controls. RESULTS AND ANALYSIS: We found a significant increase in T helper 10 (Th10) cells and IL-10 levels in SLE patients compared to controls. Disease activity, measured by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, correlated positively with Th10 cells and IL-10 levels. Further analysis categorized patients into active and inactive SLE, showing significant differences in laboratory parameters, including C3, C4, Th10 cells, and IL-10, between the two groups. Notably, Th10 cells and IL-10 exhibited a significant positive correlation with SLEDAI scores. The study also explored SLE patients with and without nephritis, a severe manifestation of the disease. Th10 cell expression was significantly higher in nephritis patients, while IL-10 levels did not differ significantly between the two groups. CONCLUSION: In conclusion, this study provides valuable insights into the association between Th10 cells, IL-10, and disease activity in SLE. The findings suggest that Th10 cells and IL-10 could serve as potential biomarkers for disease activity in SLE, offering a basis for further research into therapeutic interventions targeting these factors. These results contribute to our understanding of the complex immunological factors at play in SLE and may pave the way for more targeted and effective treatment approaches.

Use of Financial Incentives to Promote Adolescent Type 1 Diabetes Self-management: A Pilot Randomized Controlled Trial.

OBJECTIVE: To evaluate whether financial incentives lead to improvement in self-management behaviors and glycemia in adolescents with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Adolescents (12- to 18-year-olds) with T1D selected incentivized self-management behavior and clinical outcome goals in a 3-treatment (gain frame, loss frame, no incentives) crossover randomized controlled trial. Participants could earn up to $180 in each 12-week incentive treatment arm. RESULTS: Compared with a mean 41% behavioral goal attainment within the nonfinancial incentives arm, mean behavioral goal attainment under gain and loss frames was 50% (P < 0.01) and 45% (P < 0.01), respectively. Mean time in range (TIR) in gain frame and loss frame arms was higher 43% (P < 0.01) and 42% (P < 0.01), respectively, compared with when not receiving financial incentives (38%). There was no difference in A1C among the three arms. CONCLUSIONS: Financial incentives can improve diabetes self-management behaviors and TIR in adolescents with T1D in the short-term.

Adolescent-Preferred financial incentives to promote type 1 diabetes Self-Care: A discrete choice experiment.

AIMS: This study aimed to quantify preferences for the characteristics of a financial incentives program that would motivate adolescent engagement in type 1 diabetes (T1D) self-care. METHOD: We performed a discrete choice experiment with 12-18 year-olds with T1D from two pediatric hospital endocrinology clinics (n = 317). We identified key attributes of incentives: (1) monthly value of the reward, (2) payment structure, and (3) difficulty of incentivized behaviors. In twelve choice questions, adolescents chose the incentive option from a pair of profiles that was more likely to motivate them to increase adherence to recommended self-care. Options presented were tailored to adolescents' T1D technology use and perceived difficulty of completing each behavior. We analyzed data using a conditional logit model. RESULTS: The value of the reward accounted for 60.8% of preferences. Adolescents were willing to accept lower value rewards when incentive payments used positive vs. negative reinforcement (-$10.88 (95% CI: -$12.60, -9.24)) and preferred higher incentives for performing hard vs. easier behaviors (+$14.92 (95% CI: +$12.66, +$17.28)). CONCLUSIONS: Stated preferences can inform intervention design. Future research will evaluate the external validity of the discrete choice experiment-informed intervention design by assessing adolescent health and behavioral outcomes in a randomized controlled trial.

Splenic Dysfunction in Children With Sickle Cell Disease: A Single Centre Experience From Central India.

OBJECTIVE: To assess the incidence and predictors of splenic dysfunction in children with sickle cell disease (SCD). METHODS: A cross-sectional study was conducted between June 2019 and December 2020 where children aged 1 to 15 years of age with SCD were screened for splenic dysfunction. Children who were splenectomised, those with other diseases known to affect splenic function like congenital malformations, immunodeficiencies, and chronic diseases like tuberculosis, nephrotic syndrome, diabetes mellitus, chronic liver disease, celiac disease or malignancy were excluded. Splenic size was assessed by clinical examination and ultrasonography. Splenic dysfunction was assessed using splenic scintigraphy using Technetium-99m (99mTc) labeled autologous RBCs and by the presence of Howell Jolly bodies in the peripheral smear. Laboratory and clinical predictors of splenic dysfunction were assessed by multiple logistic regression. RESULTS: We evaluated 66 children with SCD with a mean (SD) age of 7.41 (3.3) years. Impaired and absent splenic function as assessed by 99mTc scintigraphy was found in 13 (19.7%), and 3 (4.6%) children, respectively. Howell Jolly bodies in peripheral smear were found in 5 (7.5%) children; 3 of them had abnormal uptake on scintigraphy; all five had splenomegaly. Age > 5 years, > 4 episodes of vaso-occlusive crisis (VOC), > 3 hospitalization events in the past, > 5 blood transfusions, children not receiving hydroxyurea, reticulocyte count > 4%, and HbS > 70% were independent predictors of splenic dysfunction. CONCLUSION: The prevalence of splenic dysfunction in children with SCD in Central India is lower than that reported from the West. The decision to start antibiotic prophylaxis can be individualized in these children.

Virtue ethics and the unsettled ethical questions in controlled human infection studies.

Controlled human infection studies (CHIs) involve the intentional infection of human subjects for a scientific aim. Though some past challenge trials have involved serious ethical abuses, in the last few decades, CHIs have had a strong track record of safety. Despite increased attention to the ethics of CHIs during the COVID-19 pandemic, CHIs remain controversial, and there has been no in-depth treatment of CHIs through the lens of virtue ethics. In this article, we argue that virtue theory can be helpful for addressing CHIs that present a constellation of controversial, unresolved, and/or under-regulated ethical issues. We begin with some brief background on virtue ethics. We then substantiate our claim that some CHIs raise a constellation of ethical issues that are unresolved in the ethics literature and/or lack adequate regulatory guidance by demonstrating that CHIs can present indeterminate social value, risks to third parties, limitations on the right to withdraw from research, and questions about the upper limit of allowable risk. We argue that the presence of a virtuous investigator, with virtues such as prudence, compassion, and integrity, is especially important when these unresolved research ethics issues arise, which is the case for certain types of controlled human infection studies. We use the historical example of Walter Reed and the Yellow Fever Commission to illustrate this claim, and we also highlight some contemporary examples. We end by sketching some practical implications of our view, such as ensuring that investigators with experience running CHIs are involved in novel CHI models.

Notes from the Field: Increases in Imported Malaria Cases - Three Southern U.S. Border Jurisdictions, 2023.

Malaria is a severe and potentially fatal mosquitoborne disease caused by infection with Plasmodium spp. parasites. Although malaria is no longer endemic in the United States, imported infections are reported annually; the primary risk group has been U.S. residents traveling to areas where malaria is endemic (1). In 2023, sporadic locally acquired mosquito-transmitted malaria cases were reported in several U.S. states (2,3). This report describes increases in imported malaria cases in 2023 compared with 2022 in three public health jurisdictions along the U.S. southern border.

Possible unintended consequences of pediatric clinician strategies for communicating about social-emotional and developmental concerns in diverse young children.

INTRODUCTION: Screening to promote social-emotional well-being in toddlers has positive effects on long-term health and functioning. Communication about social-emotional well-being can be challenging for primary care clinicians for various reasons including lack of time, training and expertise, resource constraints, and cognitive burden. Therefore, we explored clinicians' perspectives on identifying and communicating with caregivers about social-emotional risk in toddlers. METHOD: In 2021, semistructured interviews were conducted with pediatric clinicians (N = 20) practicing in Federally Qualified Health Centers in a single metropolitan area. Most participants identified as female (n = 15; 75%), white non-Hispanic/Latino (n = 14; 70%), and were Doctors of Medicine or Osteopathic Medicine (n = 14; 70%). Thematic analysis was conducted on audio-recorded interview transcripts. RESULTS: Clinicians used various approaches to identify social-emotional concerns which were sometimes difficult to distinguish from other developmental concerns. The clinician-caregiver relationship guided identification and communication practices and cut-across themes. Themes include: starting with caregivers' concerns, communicating concerns with data and sensitivity, navigating labels, culture, and stigma, and limiting communication based on family capacity and interest. DISCUSSION: Prioritizing the clinician-caregiver relationship is consistent with best practice and family-centered care. Yet, the dearth of standardized decision support may undermine clinician confidence and impede timely conversations about social-emotional concerns. An evidence-based approach with developmentally based culturally informed quantitative tools and standardized decision supports could help ensure equitable management and decision making about young children's social and emotional well-being and development. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The HI V O pen Call on I nformed C onsent and E thics in Research (VOICE) for Adolescents and Young Adults: A Digital Crowdsourcing Open Call in Low- and Middle-Income Countries.

BACKGROUND: Many adolescents and young adults (AYAs; 10-24 years old) are excluded from HIV research because of social, ethical, and legal challenges with informed consent, resulting in limited AYA-focused data. We use a participatory approach to identify strategies for improving AYA consent processes in HIV research in low- and middle-income countries (LMICs). METHODS: We conducted a digital crowdsourcing open call for ideas to improve AYA consent to HIV research in LMICs. Crowdsourcing involves engaging a group of people in problem-solving, then sharing emergent solutions. Submissions were evaluated by 3 independent judges using predefined criteria, with exceptional strategies receiving prizes. Demographic data were collected, and textual data were qualitatively analyzed for emergent themes in barriers and facilitators for improving AYA consent in HIV research, guided by a socioecological model. RESULTS: We received 110 strategies total; 65 were eligible for evaluation, 25 of which were identified as finalists. Fifty-eight participants from 10 LMICs submitted the 65 eligible submissions, of which 30 (52%) were 18 to 24 years old. Thematic analysis identified 10 barriers to AYA consent, including HIV stigma, limited education, and legal/regulatory barriers. Strategies for improving AYA consent processes revealed 7 potential facilitators: enhancing AYA engagement in research, involving parents/guardians, improving education/awareness, improving institutional practices/policy, making research participation more AYA-friendly, enhancing engagement of other key communities of interest, and empowering AYA. CONCLUSIONS: Diverse communities of interest in LMICs developed compelling strategies to enhance informed consent that may improve AYA inclusion in HIV research. These data will be used to develop practical guidance on improving AYA consent processes.

A pilot recruitment strategy to enhance ethical and equitable access to Covid-19 pediatric vaccine trials.

BACKGROUND/AIMS: The SARS-CoV-2 pandemic disproportionately impacted communities with lower access to health care in the United States, particularly before vaccines were widely available. These same communities are often underrepresented in clinical trials. Efforts to ensure equitable enrollment of participants in trials related to treatment and prevention of Covid-19 can raise concerns about exploitation if communities with lower access to health care are targeted for recruitment. METHODS: To enhance equity while avoiding exploitation, our site developed and implemented a three-part recruitment strategy for pediatric Covid-19 vaccine studies. First, we publicized a registry for potentially interested participants. Next, we applied public health community and social vulnerability indices to categorize the residence of families who had signed up for the registry into three levels to reflect the relative impact of the pandemic on their community: high, medium, and low. Finally, we preferentially offered study participation to interested families living in areas categorized by these indices as having high impact of the Covid-19 pandemic on their community. RESULTS: This approach allowed us to meet goals for study recruitment based on public health metrics related to disease burden, which contributed to a racially diverse study population that mirrored the surrounding community demographics. While this three-part recruitment strategy improved representation of minoritized groups from areas heavily impacted by the Covid-19 pandemic, important limitations were identified that would benefit from further study. CONCLUSION: Future use of this approach to enhance equitable access to research while avoiding exploitation should test different methods to build trust and communicate with underserved communities more effectively.

Ethical and Legal Obligations for Research Involving Pregnant Persons in a Post-Dobbs Context.

In light of a history of categorical exclusion, it is critical that pregnant people are included in research to help improve the knowledge base and interventions needed to address public health. Yet the volatile legal landscape around reproductive rights in the United States threatens to undue recent progress made toward the greater inclusion of pregnant people in research. We offer ethical and practical guidance for researchers, sponsors, and institutional review boards to take specific steps to minimize legal risks and ensure the ethical conduct of research with pregnant people in an evolving legal environment.

Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics.

The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of "local" when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation.

'I feel that I should decide on my own .': who should be involved in the decision-making process for adolescent involvement in HIV research?

INTRODUCTION: Efforts to improve health outcomes among adolescents and young adults living with HIV (ALHs) are hampered by limited adolescent engagement in HIV-related research. We sought to understand the views of adolescents, caregivers and healthcare workers (HCWs) about who should make decisions regarding ALHs' research participation. METHODS: We conducted focus group discussions (FGDs) and in-depth interviews (IDIs) with ALHs (aged 14-24 years), caregivers of ALHs and HCWs from six HIV care clinics in Western Kenya. We used semi-structured guides to explore ALHs' involvement in research decisions. Transcripts were analysed using thematic analysis; perspectives were triangulated between groups. RESULTS: We conducted 24 FGDs and 44 IDIs: 12 FGDs with ALHs, 12 with caregivers, and 44 IDIs with HCWs, involving 216 participants. HCWs often suggested that HIV research decision-making should involve caregivers and ALHs deciding together. In contrast, ALHs and parents generally thought decisions should be made individually, whether by HCWs/research teams (although this is likely ethically problematic), adolescents or caregivers. Caregiver and ALH preferences depended on ALHs' age, with younger ALHs requiring more support. A few caregivers felt that ALHs should consult with the research team/HCWs due to their greater knowledge of clinical care. ALHs emphasised that they should independently decide because they thought they had the right to do so and the capacity to consent. Poor communication and parental non-disclosure of HIV status influenced ALHs' views to exclude caregivers from decision-making. Regarding influences on research decision-making, ALHs were more willing to participate based on perceived contribution to science and less interested in participating in studies with potential risks, including loss of confidentiality. DISCUSSION: While research teams and HCWs felt that adolescents and caregivers should jointly make research decisions, ALHs and caregivers generally felt individuals should make decisions. As ALHs sometimes find caregiver support lacking, improving family dynamics might enhance research engagement.

An Approach to Re-evaluate the Reference Cutoff of the Parameters of Newborn Screening: An Observational Study.

Background Unless a cutoff level of the parameters of newborn screening (NBS) is defined, a screening test's results would end in high recall rates and apprehensive parents. The study aimed to establish a cutoff level of the healthy term newborns. Materials and methods The study was a retrospective observational data analysis on a cohort of 1158 term newborns who underwent NBS in our institute. The percentile distribution of the NBS parameters was computed and the 99th percentile value was considered the new cutoff. For lower values, such as neonatal glucose 6-phosphate dehydrogenase (nG6PD) and neonatal biotinidase (nBIOT), low percentile values were regarded as new cutoff value. Results Neonatal thyroid stimulating hormone (nTSH), nG6PD, neonatal immunoreactive trypsinogen (nIRT), and nBIOT showed a wide variation in the distribution. Most newborns had neonatal galactose (nGAL), nIRT, and nBIOT values above the median. The 99th percentile value of nTSH was 14.5 mIU/L, and that of neonatal 17-hydroxyprogesterone (n17-OHP) was 43.7 nmol/L. The 1.0th percentile value for nG6PD was decreased to 2.18 IU/gHb. The new cutoff values for nBIOT, nIRT, neonatal phenylketonuria (nPKU) and nGAL were 48.59 U, 95.3 µg/L, 2.3 mg/dL and 15.9 mg/dL. The mean and median nTSH values did not significantly differ (p=0.99) in the first five days of birth. On the contrary, the study population depicted considerably raised levels of n17-OHP on day 3, followed by a sharp decrease (p=0.029). Similarly, nIRT displayed significant differences in the first five days (p=0.017). Conclusion Using the 99th percentile values of the NBS parameters as the new cutoff levels might be beneficial in terms of the recall rates and cost burden.

Shigellosis outbreak among persons experiencing homelessness-San Diego County, California, October-December 2021.

During October 2021, the County of San Diego Health and Human Services Agency identified five cases of shigellosis among persons experiencing homelessness (PEH). We conducted an outbreak investigation and developed interventions to respond to shigellosis outbreaks among PEH. Confirmed cases occurred among PEH with stool-cultured Shigella sonnei; probable cases were among PEH with Shigella-positive culture-independent diagnostic testing. Patients were interviewed to determine infectious sources and risk factors. Fifty-three patients were identified (47 confirmed, 6 probable); 34 (64%) were hospitalised. None died. No point source was identified. Patients reported inadequate access to clean water and sanitation facilities, including public restrooms closed because of the COVID-19 pandemic. After implementing interventions, including handwashing stations, more frequent public restroom cleaning, sanitation kit distribution, and isolation housing for ill persons, S. sonnei cases decreased to preoutbreak frequencies. Improving public sanitation access was associated with decreased cases and should be considered to prevent outbreaks among PEH.

A Novel Mutation in Cystic Fibrosis Presenting as Pseudo Bartter Syndrome: A Case Report.

Pseudo-Bartter's (PB) syndrome is characterized by hypokalemic metabolic alkalosis and failure to thrive which constitutes a rare but typical presentation of cystic fibrosis (CF) in children. The most common mutation of CF is F508del, due to loss of 3 base pairs, causing deletion of phenylalanine, at position 508. We present a case of CF presenting with failure to thrive, dehydration, PB syndrome associated with urosepsis and primo-colonization with Escherichia coli suggesting the role of epigenetic factors. The heterozygous state for Phe508del mutation in Exon 11 combination with Glu92Ala in Exon 4 resulted in epigenetic effect on atypical phenotype as PBS, a novel mutation identified in our case.

"Liver Failure in an Infant of Late-Onset Glutaric Aciduria Type II": Case Report.

Glutaric aciduria type II, also known as Multiple acyl-CoA Dehydrogenase Deficiency, results from a defect in the mitochondrial electron transport chain resulting in an inability to break down fatty-acids and amino acids. There are three phenotypes- type 1 and 2 are of neonatal onset and severe form, with and without congenital anomalies, respectively, and presents with acidosis, severe hypotonia, cardiomyopathy, hepatomegaly, and non-ketotic hypoglycemia. Type 3 or late-onset Multiple acyl-CoA Dehydrogenase Deficiency usually presents in the adolescent or adult age group with phenotype ranging from mild forms of myopathy and exercise intolerance to severe forms of acute metabolic decompensation on its chronic course. Type 3 Multiple acyl-CoA Dehydrogenase Deficiency rarely presents in infancy and in liver failure. We present a five-month-old developmentally normal female child with acute encephalopathy, hypotonia, non-ketotic hypoglycemia, metabolic acidosis, and liver failure, with a history of sibling death of suspected inborn error of metabolism. The blood acyl-carnitine levels in Tandem Mass Spectrometry and urinary organic acid analysis through Gas Chromatography-Mass Spectrometry were unremarkable. The patient initially responded to riboflavin, CoQ, and supportive management but ultimately succumbed to sepsis with shock and multi-organ dysfunction. The clinical exome sequencing reported a homozygous missense variation in exon 11 of the ETFDH gene (chr4:g.158706270C > T) that resulted in the amino acid substitution of Leucine for Proline at codon 456 (p.Pro456Leu) suggestive of Glutaric aciduria type IIc (OMIM#231,680).

Patient priorities for fulfilling the principle of respect in research: findings from a modified Delphi study.

BACKGROUND: Standard interpretations of the ethical principle of respect for persons have not incorporated the views and values of patients, especially patients from groups underrepresented in research. This limits the ability of research ethics scholarship, guidance, and oversight to support inclusive, patient-centered research. This study aimed to identify the practical approaches that patients in community-based settings value most for conveying respect in genomics research. METHODS: We conducted a 3-round, web-based survey using the modified Delphi technique to identify areas of agreement among English-speaking patients at primary care clinics in Washington State and Idaho who had a personal or family history of cancer. In Round 1, respondents rated the importance of 17 items, identified in prior qualitative work, for feeling respected. In Round 2, respondents re-rated each item after reviewing overall group ratings. In Round 3, respondents ranked a subset of the 8 most highly rated items. We calculated each item's mean and median rankings in Round 3 to identify which approaches were most important for feeling respected in research. RESULTS: Forty-one patients consented to the survey, 21 (51%) completed Round 1, and 18 (86% of Round 1) completed each of Rounds 2 and 3. Two sets of rankings were excluded from analysis as speed of response suggested they had not completed the Round 3 ranking task. Respondents prioritized provision of study information to support decision-making (mean ranking 2.6 out of 8; median ranking 1.5) and interactions with research staff characterized by kindness, patience, and a lack of judgment (mean ranking 2.8; median ranking 2) as the most important approaches for conveying respect. CONCLUSIONS: Informed consent and interpersonal interactions are key ways that research participants experience respect. These can be supported by other approaches to respecting participants, especially when consent and/or direct interactions are infeasible. Future work should continue to engage with patients in community-based settings to identify best practices for research without consent and examine unique perspectives across clinical and demographic groups in different types of research.

Evidence of kinesin motors involved in stable kinetochore assembly during early meiosis.

During mitosis, the budding yeast, kinetochores remain attached to microtubules, except for a brief period during S phase. Sister-kinetochores separate into two clusters (bilobed organization) upon stable end-on attachment to microtubules emanating from opposite spindle poles. However, in meiosis, the outer kinetochore protein (Ndc80) reassembles at the centromeres much later after prophase I, establishing new kinetochore-microtubule attachments. Perhaps due to this, despite homolog bi-orientation, we observed that the Ndc80 are linearly dispersed between spindle poles during metaphase I of meiosis. The presence of end-on attachment marker Dam1 as a cluster near each pole suggests one of the other possibilities that the pole-proximal and pole-distal kinetochores are attached end-on and laterally to the microtubules, respectively. Colocalization studies of kinetochores and kinesin motors suggest that budding yeast kinesin 5, Cin8, and Kip1 perhaps localize to the end-on attached kinetochores while kinesin 8 and Kip3 resides at all the kinetochores. Our findings, including kinesin 5 and Ndc80 coappearance after prophase I and reduced Ndc80 levels in cin8 null mutant, suggest that kinesin motors are crucial for kinetochore reassembly and stability during early meiosis. Thus, this work reports yet another meiosis specific function of kinesin motors.

Possible Exposures Among Mpox Patients Without Reported Male-to-Male Sexual Contact - Six U.S. Jurisdictions, November 1-December 14, 2022.

The extent to which the 2022 mpox outbreak has affected persons without a recent history of male-to-male sexual contact (MMSC) is not well understood. During November 1-December 14, 2022, CDC partnered with six jurisdictional health departments to characterize possible exposures among mpox patients aged ≥18 years who did not report MMSC during the 3 weeks preceding symptom onset. Among 52 patients included in the analysis, 14 (27%) had a known exposure to a person with mpox, including sexual activity and other close intimate contact (eight) and household contact (six). Among 38 (73%) patients with no known exposure to a person with mpox, self-reported activities before illness onset included sexual activity and other close intimate contact (17; 45%), close face-to-face contact (14; 37%), attending large social gatherings (11; 29%), and being in occupational settings involving close skin-to-skin contact (10; 26%). These findings suggest that sexual activity remains an important route of mpox exposure among patients who do not report MMSC.