Transcranial Direct Current Stimulation Reduces Pressure Pain Sensitivity in Patients with Non-Malignant Chronic Pain.

OBJECTIVES: Non-malignant chronic pain is a clinical challenge because pharmacological treatment often fails to relieve pain. Transcranial direct current stimulation (tDCS) is a treatment that could have the potential for pain relief and improvement in quality of life. However, there is a lack of clinical trials evaluating the effects of tDCS on the pain system. The aim of the present study was to evaluate the effect of 5 days of anodal tDCS treatment on the pain system in chronic non-malignant pain patients using quantitative sensory testing (QST) and quality of life questionnaires: (1) Brief Pain Inventory-short form (BPI-sf), (2) European Organization for Research and Treatment of Life Questionnaire (EORTC-C30), and (3) Hospital Anxiety Depression Scale (HADS). METHODS: Eleven non-malignant chronic pain patients (51±13.6 years old, 5M) participated in the study. Anodal tDCS was applied for five consecutive days, followed by sham stimulation after a washout period of at least two weeks. Pressure pain thresholds (PPT) and pain tolerance thresholds (PTT) were assessed in different body regions on days 1 and 5. RESULTS: Anodal tDCS appeared to maintain PTT at C5 (clavicle) on day 5, but sham stimulation decreased PTT (P=0.007). Additionally, anodal tDCS increased PTT compared to sham at day 5 at Th10 ventral dermatomes (P=0.014). Both anodal and sham tDCS decreased the BPI-sf total and interference scores, and the EORTC-C30 fatigue score, but no interaction effect was observed. DISCUSSION: This study adds to the evidence in the literature that tDCS may be a potential therapeutic tool for the management of non-malignant chronic pain.

Musculoskeletal Symptoms and Misdiagnoses in Children With Acute Myeloid Leukaemia: A Nationwide Cohort Study.

OBJECTIVES: Childhood cancer often presents with non-specific signs and symptoms that might mimic non-malignant disorders including musculoskeletal diseases, potentially leading to rheumatic and orthopaedic misdiagnoses. We aimed to compare clinical presentation, diagnostic interval and survival in paediatric acute myeloid leukaemia (AML) with and without initial musculoskeletal symptoms. METHODS: This nationwide retrospective, cohort study reviewed medical records of 144 children below 15 years diagnosed with AML in Denmark from 1996 to 2018. RESULTS: Musculoskeletal symptoms occurred in 29% (42/144) of children with AML and 8% (11/144) received an initial musculoskeletal misdiagnosis, being mainly non-specific and pain-related. The children with and without musculoskeletal symptoms did not differ markedly up to the diagnosis of AML and blood counts were affected equally in both groups. However, the children with prior musculoskeletal symptoms were more likely to have elevated levels of LDH and ferritin. Furthermore, they revealed a tendency towards a longer total interval (median 53 days vs. 32 days, p = 0.07), but the overall survival did not differ. CONCLUSION: AML should be considered as an underlying cause in children with unexplained musculoskeletal symptoms and abnormal blood counts. Concomitant elevation of LDH and ferritin should strengthen the suspicion.

Court Navigators and Opportunities for Disseminating Overdose Prevention Strategies.

Objective. Describe how navigator programs from three New England states (Connecticut, Maine, and Massachusetts) function to connect individuals using court services to community-based treatment and services. Hypothesis. Implementation science frameworks can be used to analyze how multiple court programs function to inform replication and address gaps in the use of overdose prevention strategies. Method. The Template for Intervention Description and Replication (TIDieR) Implementation informed semi-structured interviews as part of an exploratory mixed-methods analysis of court navigator programs. Analysis of interviews based on the TIDieR and administrative data on client contacts (n = 436) were analyzed. A subsample of clients with additional background information (n = 249) was used to examine court navigator recommendations. Results. The TIDieR revealed court navigator programs shared basic intervention characteristics but varied dramatically by resources and organization contexts. Nearly half (46.5%) of clients were self-referred and more than two-thirds (69.1%) approved follow-up but varied by program. Of those allowing follow-up, more than one-third (35.7%) had previously experienced an overdose. Court navigators were significantly more likely to refer clients with a history of overdose to locations where they can receive naloxone (the opioid overdose antidote) though only one program had naloxone on hand. Conclusion. Navigators are employed by community organizations with access to courthouses to provide resources to those passing through. These efforts can be implemented to support linkages to treatment and services but there is a significant gap in the allocation of overdose prevention strategies in court settings and court navigator programs have the potential to address this unmet need.

Early Adversity and Socioeconomic Factors in Pediatric Multiple Sclerosis: A Case-Control Study.

BACKGROUND AND OBJECTIVES: Psychosocial adversity and stress, known to predispose adults to neurodegenerative and inflammatory immune disorders, are widespread among children who experience socioeconomic disadvantage, and the associated neurotoxicity and proinflammatory profile may predispose these children to multiple sclerosis (MS). We sought to determine associations of socioeconomic disadvantage and psychosocial adversity with odds of pediatric-onset MS (POMS), age at POMS onset, and POMS disease activity. METHODS: This case-control study used data collected across 17 sites in the United States by the Environmental and Genetic Risk Factors for Pediatric Multiple Sclerosis Study. Cases (n = 381) were youth aged 3-21 years diagnosed with POMS or a clinically isolated demyelinating syndrome indicating high risk of MS. Frequency-matched controls (n = 611) aged 3-21 years were recruited from the same institutions. Prenatal and postnatal adversity and postnatal socioeconomic factors were assessed using retrospective questionnaires and zip code data. The primary outcome was MS diagnosis. Secondary outcomes were age at onset, relapse rate, and Expanded Disability Status Scale (EDSS). Predictors were maternal education, maternal prenatal stress events, child separation from caregivers during infancy and childhood, parental death during childhood, and childhood neighborhood disadvantage. RESULTS: MS cases (64% female, mean age 15.4 years, SD 2.8) were demographically similar to controls (60% female, mean age 14.9 years, SD 3.9). Cases were less likely to have a mother with a bachelor's degree or higher (OR 0.42, 95% CI 0.22-0.80, p = 0.009) and were more likely to experience childhood neighborhood disadvantage (OR 1.04 for each additional point on the neighborhood socioeconomic disadvantage score, 95% CI 1.00-1.07; p = 0.025). There were no associations of the socioeconomic variables with age at onset, relapse rate, or EDSS, or of prenatal or postnatal adverse events with risk of POMS, age at onset, relapse rate, or EDSS. DISCUSSION: Low socioeconomic status at the neighborhood level may increase the risk of POMS while high parental education may be protective against POMS. Although we did not find associations of other evaluated prenatal or postnatal adversities with POMS, future research should explore such associations further by assessing a broader range of stressful childhood experiences.

Second Primary Lung Cancer - An Emerging Issue in Lung Cancer Survivors.

As a result of an increased focus on early detection including lung cancer screening, combined with more curative treatment options, the 5-year survival rates for lung cancer are improving. Welcome though this is, it brings new, hitherto unseen challenges. As more patients are cured and survive longer, they are at risk of developing second primary cancers, particularly lung cancer. In this review, we examine the challenges that surveillance, diagnosis, and management of second primary lung cancer (SPLC) bring and how these can be addressed. Recent data from prospective follow-up studies suggests that the incidence of SPLC may be higher than previously appreciated, partly due to an increase in multi-focal adenocarcinoma spectrum disease. Over 5 years, up to 1 in 6 long-term lung cancer survivors may develop a SPLC. Although not routinely used in clinical practice at present, genomic approaches for differentiating SPLC from intrapulmonary metastases of the first primary are emerging, and we highlight how this could be used to help differentiate lesions. An accurate distinction between SPLC and the recurrence of the first primary is of paramount importance due to the very different management strategies that may be required. Wrongly classifying an SPLC as a recurrence of the first primary may have significant consequences for patient management and overall survival. Updated approaches to the classification of SPLC combining clinical history, histopathological assessment, and genomic profiling are needed. Finally, we review the potential role of early detection biomarkers in the identification of SPLC, focusing in particular on blood-based biomarkers that are being examined in a multi-center prospective study recruiting lung cancer survivors.

Ultrasensitive plasma-based monitoring of tumor burden using machine-learning-guided signal enrichment.

In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole-genome sequencing (WGS). Here we now introduce MRD-EDGE, a machine-learning-guided WGS ctDNA single-nucleotide variant (SNV) and copy-number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGESNV uses deep learning and a ctDNA-specific feature space to increase SNV signal-to-noise enrichment in WGS by ~300× compared to previous WGS error suppression. MRD-EDGECNV also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1 Gb to 200 Mb, vastly expanding its applicability within solid tumors. We harness the improved performance to identify MRD following surgery in multiple cancer types, track changes in TF in response to neoadjuvant immunotherapy in lung cancer and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal-to-noise enrichment in MRD-EDGESNV enables plasma-only (non-tumor-informed) disease monitoring in advanced melanoma and lung cancer, yielding clinically informative TF monitoring for patients on immune-checkpoint inhibition.

Error-Corrected Deep Targeted Sequencing of Circulating Cell-Free DNA from Colorectal Cancer Patients for Sensitive Detection of Circulating Tumor DNA.

Circulating tumor DNA (ctDNA) is a promising biomarker, reflecting the presence of tumor cells. Sequencing-based detection of ctDNA at low tumor fractions is challenging due to the crude error rate of sequencing. To mitigate this challenge, we developed ultra-deep mutation-integrated sequencing (UMIseq), a fixed-panel deep targeted sequencing approach, which is universally applicable to all colorectal cancer (CRC) patients. UMIseq features UMI-mediated error correction, the exclusion of mutations related to clonal hematopoiesis, a panel of normal samples for error modeling, and signal integration from single-nucleotide variations, insertions, deletions, and phased mutations. UMIseq was trained and independently validated on pre-operative (pre-OP) plasma from CRC patients (n = 364) and healthy individuals (n = 61). UMIseq displayed an area under the curve surpassing 0.95 for allele frequencies (AFs) down to 0.05%. In the training cohort, the pre-OP detection rate reached 80% at 95% specificity, while it was 70% in the validation cohort. UMIseq enabled the detection of AFs down to 0.004%. To assess the potential for detection of residual disease, 26 post-operative plasma samples from stage III CRC patients were analyzed. From this we found that the detection of ctDNA was associated with recurrence. In conclusion, UMIseq demonstrated robust performance with high sensitivity and specificity, enabling the detection of ctDNA at low allele frequencies.

A novel referral strategy to enhance the enrollment of patients with heart failure in cardiac rehabilitation: A feasibility study.

Background and Aims: Rehabilitation targeting patients with cardiac conditions are evident and acknowledged in clinical guidelines. However, participation rates remain suboptimal, with only 50% of all patients with cardiac conditions participating in these programs across Europe. Considering the well-documented effects of rehabilitation, increasing the referral rate to cardiac rehabilitation would be desirable. This study aimed to evaluate the feasibility of a novel referral strategy that could potentially enhance enrollment in cardiac rehabilitation for patients with heart failure. Methods: This prospective feasibility study incorporating both quantitative and qualitative methods was conducted in an outpatient heart failure clinic and a municipal health care center. 106 patients with heart failure were referred to the heart failure clinic from September 2021 through July 2022. A 15-20 min face-to-face physiotherapy consultation was incorporated into usual care, evaluating patients' habitual and actual level of functioning, disability, and physical activity and assessing their potential need and motivation for cardiac rehabilitation. Three predefined quantitative feasibility outcomes: reach, referral rate, and data completeness were assessed. Additionally, semi-structured interviews explored acceptability among patients and health care professionals at the municipal health care center and the hospital. Finally, the potential effect was assessed based on the enrollment rate. Results: Physiotherapy consultations were offered to 86% of eligible patients; of these, 52% were referred to cardiac rehabilitation. Ninety-one percent data completeness was achieved. The intervention was well-accepted by patients and health care professionals. The enrollment rate reached 79%. Conclusion: The novel referral strategy proved feasible concerning reach and data completeness, although the referral rate suggested that further refinements are required before a full-scale trial. The novel referral strategy was well-accepted, and enrollment rate approached an acceptable level.

Growing pains in Danish preschool children: a descriptive study.

This study provides a detailed description of growing pains in young Danish children as standardized diagnostic criteria are needed to avoid misclassifications of other musculoskeletal diagnoses. The study is nested in a cohort study of Danish preschool children. At baseline, parents completed a questionnaire with sociodemographic information. During the study, the parents received a text message every two weeks inquiring about musculoskeletal pain in the child. If pain was reported, a telephone interview about pain characteristics was conducted. The present study includes data from 2016 to 2019 with 777 children, aged 3-6 years of age at baseline. The prevalence of growing pains was 24-43%, depending on the definition. The pain occurred most frequently 1-3 times per week and most commonly in the lower legs, could be unilateral or bilateral and was usually without consequences. The prevalence increased with age, and there were no consistent associations with socio-economic factors. We suggest using Evan's criteria with the addition of unilateral pain as standard diagnostic criteria in the future. We found no relation to periods of rapid growth and suggest that the term is a misnomer. Etiology and long-term courses of pain need to be explored in future studies.

Lying is sometimes ethical, but honesty is the best policy: The desire to avoid harmful lies leads to moral preferences for unconditional honesty.

People believe that some lies are ethical, while also claiming that "honesty is the best policy." In this article, we introduce a theory to explain this apparent inconsistency. Even though people view prosocial lies as ethical, they believe it is more important-and more moral-to avoid harmful lies than to allow prosocial lies. Unconditional honesty (simply telling the truth, without finding out how honesty will affect others) is therefore seen as ethical because it prevents the most unethical actions (i.e., harmful lies) from occurring, even though it does not optimize every moral decision. We test this theory across five focal experiments and 10 supplemental studies. Consistent with our account, we find that communicators who tell the truth without finding out how honesty will affect others are viewed as more ethical, and are trusted more, than communicators who look for information about the social consequences of honesty before communicating. However, the moral preference for unconditional honesty attenuates when it is certain that looking for more information will not lead to harmful lies. Overall, this research provides a holistic understanding of how people think about honesty and suggests that moral rules are not valued because people believe all rule violations are wrong, but rather, because they believe some violations must be avoided entirely. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Health-related quality of life in people with different diabetes-related foot ulcer health states: A cross-sectional study of healed, non-infected, infected, hospitalised and amputated ulcer states.

AIMS: Diabetes-related foot ulcers (DFU) are a leading cause of infection, hospitalisation and amputation. However, to our knowledge no studies have compared the health-related quality of life (HRQoL) of people with DFU that were infected, hospitalised or amputated. This study aimed to investigate and compare the HRQoL of different groups of people with healed, non-infected, infected, hospitalised, or amputated DFU. METHODS: This was a multi-centre cross-sectional study measuring the HRQoL of patients, attending one of 18 Diabetic Foot Services across Queensland, Australia, with one of five DFU health states: healed, non-infected, infected, hospitalised, amputated. HRQoL was measured using the EQ-5D-5L to estimate age-sex adjusted utility values. RESULTS: Of 376 included patients (mean age 63 (12) years, 75% male), age-sex adjusted HRQoL utility estimates (95% CIs) were: healed DFU 0.57 (0.51-0.64), non-infected DFU 0.55 (0.49-0.62), infected DFU 0.45 (0.36-0.55), hospitalised DFU 0.53 (0.42-0.64), and amputated DFU 0.55 (0.46-0.63). CONCLUSION: People in any DFU health state have considerably reduced HRQoL, with greatest reductions in those with infected DFU. These findings provide valuable HRQoL estimates and comparisons for several different important DFU health states, adding to our understanding of the impact of DFU on HRQoL and facilitating future economic evaluations.

Measuring the cost-effectiveness of a home-visiting intervention to promote early child development among rural families linked to the Rwandan social protection system.

Early childhood development (ECD) programmes are heralded as a way to improve children's health and educational outcomes. However, few studies in developing countries calculate the effectiveness of quality early childhood interventions. This study estimates the cost and cost-effectiveness of the Sugira Muryango (SM) trial, a home-visiting intervention to improve ECD outcomes through positive parent-child relationships. Cost-effectiveness analysis of ECD interventions is challenging given their potential to have multiple benefits. We propose a cost-effectiveness method using a single outcome, in this case the improvement in cognitive development per home-visit session, as an indication of efficiency comparable across similar interventions. The trial intervention cost US$456 per family. This cost will likely fall below US$200 if the intervention is scaled through government systems. The cost-effectiveness analysis suggests that while SM generated a relatively small impact on markers of early development, it did so efficiently. The observed improvements in cognitive development per home-visit are similar to other home-visiting interventions of longer duration. SM by focusing on the family had benefits beyond ECD, including reductions in violence against children and intermate partner violence, further analysis is needed to include these returns in the economic evaluation.

Low- versus standard- pneumoperitoneum in patients undergoing robot-assisted radical prostatectomy: a randomised, triple-blinded study.

OBJECTIVE: To investigate the effectiveness and impact of low-pressure pneumoperitoneum (Pnp) on postoperative quality of recovery (QoR) and surgical workspace (SWS) in patients with prostate cancer undergoing robot-assisted radical prostatectomy (RARP). PATIENTS AND METHODS: A randomised, triple-blinded trial was conducted in a single centre in Denmark from March 2021 to January 2022. A total of 98 patients with prostate cancer undergoing RARP were randomly assigned to either low-pressure Pnp (7 mmHg) or standard-pressure Pnp (12 mmHg). Co-primary outcomes were postoperative QoR measured via the QoR-15 questionnaire on postoperative Day 1 (POD1), POD3, POD14, and POD30, and SWS assessed intraoperatively by a blinded assessor (surgeon) via a validated SWS scale. Data analysis was performed according to the intention-to-treat principle. RESULTS: Patients who underwent RARP at low Pnp pressure demonstrated better postoperative QoR on POD1 (mean difference = 10, 95% confidence interval [CI] 4.4-15.5), but no significant differences were observed in the SWS (mean difference = 0.25, 95% CI -0.02 to 0.54). Patients allocated to low-pressure Pnp experienced statistically higher blood loss than those in the standard-pressure Pnp group (mean difference = 67 mL, P = 0.01). Domain analysis revealed significant improvements in pain (P = 0.001), physical comfort (P = 0.007), and emotional state (P = 0.006) for patients with low-pressure Pnp. This trial was registered at ClinicalTrials.gov, NCT04755452, on 16/02/2021. CONCLUSION: Performing RARP at low Pnp pressure is feasible without compromising the SWS and improves postoperative QoR, including pain, physical comfort, and emotional state, compared to the standard pressure.

Systemic Cytokine Expression in Diabetes Is Associated with Prolonged Gastrointestinal Transit Times and Cardinal Gastroparesis Symptoms.

Gastroenteropathy is a common complication in diabetes associated with damages to the enteric nervous system. Systemic low-grade inflammation facilitates neurotoxicity, and associations with peripheral and autonomic neuropathy have been reported. However, less is known of associations with gastroenteropathy. To explore the area cross-sectionally, we included individuals with diabetes (type 1: 56, type 2: 100) and 21 healthy controls. Serum levels of interleukin (IL)-6, IL-8, IL-10, tumour necrosis factor (TNF)-α, and interferon (IFN)-γ were measured by multiplex technology. Segmental gastrointestinal transit times were assessed by wireless motility capsule investigations. Symptoms of gastroparesis were rated on Gastroparesis Cardinal Symptom Index questionnaires. Compared to healthy, levels of TNF-α were decreased in type 1 diabetes and increased in type 2 diabetes, while colonic transit time was increased (all p < 0.05). In diabetes, associations between IL-8 and prolonged gastric emptying (odds ratio (OR) 1.07, p = 0.027) and between IL-10 and prolonged colonic transit (OR 29.99, p = 0.013) were seen. Inverse correlations between IL-6 and nausea/vomiting (rho = -0.19, p = 0.026) and bloating (rho = -0.29; p < 0.001) were found. These findings indicate a plausible interaction between inflammation and the enteric nervous system in diabetes, which raises the question of whether anti-inflammatory strategies could be applied in management of diabetic gastroenteropathy.

Family Violence Reduction Within a Parenting Intervention in Rwanda: A Mixed-Methods Study.

BACKGROUND AND OBJECTIVES: A mixed-methods study of mechanisms of change through which a home-visiting-based early childhood development intervention, Sugira Muryango ("strong family"), reduced violent discipline and intimate partner violence in Rwanda. METHODS: The cluster-randomized trial of Sugira Muryango enrolled socioeconomically vulnerable families with children aged 6 to 36 months in rural Rwanda. We interviewed 18 female caregivers early in the intervention, and 21 female caregivers and 11 male intimate partners were interviewed after the intervention. Coded interviews identify risk factors for violence and mechanisms of intervention-related change in violence. Quantitative analyses included 931 caregivers (52.6% female) who lived with an intimate partner to examine risk factors for violence, intervention effects, and mechanisms of violence reduction. RESULTS: The qualitative data identified daily hardships and alcohol problems as risk factors for violent discipline and intimate partner violence. Through Sugira Muryango, caregivers learned that strong relationships between partners and engagement of male caregivers in child care has positive impacts on children's development. Techniques taught by community lay workers improved communication, promoted positive parent-child interactions, and reduced intimate partner violence and violent discipline. Quantitative analyses also found that daily hardships predict violent discipline and intimate partner violence. Sugira Muryango reduced violent discipline, increased father engagement, and increased female caregiving warmth. Moreover, pre- to postintervention change in caregiving warmth was associated with reduced use of violent discipline among female caregivers and marginally associated with reduced female victimization. CONCLUSIONS: Violence reduction can be integrated into early child development programs to reduce violent discipline and intimate partner violence.

EHBP1L1 Frameshift Deletion in English Springer Spaniel Dogs with Dyserythropoietic Anemia and Myopathy Syndrome (DAMS) or Neonatal Losses.

Hereditary myopathies are well documented in dogs, whereas hereditary dyserythropoietic anemias are rarely seen. The aim of this study was to further characterize the clinical and clinicopathological features of and to identify the causative genetic variant for a dyserythropoietic anemia and myopathy syndrome (DAMS) in English springer spaniel dogs (ESSPs). Twenty-six ESSPs, including five dogs with DAMS and two puppies that died perinatally, were studied. Progressive weakness, muscle atrophy-particularly of the temporal and pelvic muscles-trismus, dysphagia, and regurgitation due to megaesophagus were observed at all ages. Affected dogs had a non-regenerative, microcytic hypochromic anemia with metarubricytosis, target cells, and acanthocytes. Marked erythroid hyperplasia and dyserythropoiesis with non-orderly maturation of erythrocytes and inappropriate microcytic metarubricytosis were present. Muscle biopsies showed centralized nuclei, central pallor, lipocyte infiltrates, and fibrosis, which was consistent with centronuclear myopathy. The genome sequencing of two affected dogs was compared to 782 genomes of different canine breeds. A homozygous frameshift single-base deletion in EHBP1L1 was identified; this gene was not previously associated with DAMS. Pedigree analysis confirmed that the affected ESSPs were related. Variant genotyping showed appropriate complete segregation in the family, which was consistent with an autosomal recessive mode of inheritance. This study expands the known genotype-phenotype correlation of EHBP1L1 and the list of potential causative genes in dyserythropoietic anemias and myopathies in humans. EHBP1L1 deficiency was previously reported as perinatally lethal in humans and knockout mice. Our findings enable the genetic testing of ESSP dogs for early diagnosis and disease prevention through targeted breeding strategies.

Validation of a dry-slide immunoassay for progesterone analysis in canine plasma in a clinical setting.

BACKGROUND: The identification of canine ovulation is critical for successful breeding. Progesterone measurements are useful for identifying ovulation. Progesterone assays are also quantitative and easily accessed, making them valuable in veterinary practice. OBJECTIVES: We aimed to validate a dry-slide immunoassay (DSI) for use in dogs, including a method comparison with the chemiluminescence assay (CLIA) and mass spectrometry. METHODS: Twenty-nine bitches were prospectively recruited. Accuracy, precision, interference, and stability were evaluated. Method comparison between DSI and CLIA and mass spectrometry was conducted, and bias was calculated. RESULTS: Repeatability was 8.0%-10.8%, and within-laboratory imprecision was 8.8%-11.1% for four concentration levels. Recovery under dilution was 61%-100%, and the method was linear to a concentration of ~50 nmol/L. Recovery after the addition of a high progesterone sample was 76%-83%. Minor changes were seen in one hemolytic and two lipemic samples. Storage at room temperature for 12-24 hours resulted in concentrations that were 57%-96% of the initial concentrations. For samples frozen at -80°C, the concentrations were reduced 17%-27%. There was a significant difference between results from the DSI and CLIA, and a proportional bias was seen when DSI was compared with mass spectrometry, where CLIA correlated better than DSI. CONCLUSIONS: Precision and accuracy were acceptable. A proportional bias was seen between DSI and CLIA. A small amount of interference was seen with hemolysis and lipemia. Progesterone concentrations were decreased in samples stored at room temperature and -80°C. The results support the use of the DSI for ovulation timing but not for artificial insemination with frozen semen since progesterone concentrations might exceed the assay's linearity and precision limits.

Prenatal Considerations and Outcomes for Girls Aged 14 and Under: Development of a Multidisciplinary Team in a Large Tertiary Care Facility.

INTRODUCTION: Adolescent girls account for 11% of all births that occur globally every year. Among developing countries, the United States continues to have one of the highest adolescent birth rates, despite a decreasing trend between 1990 and 2010. Pregnant adolescents are a vulnerable population who are at increased risk for maternal morbidity and mortality. Additional risks are noted within the early adolescent population, usually defined as age 10 to 14. PROCESS: At Parkland hospital, a large tertiary care facility in Dallas, Texas, a multidisciplinary team was created in 2017 to care for this vulnerable population. The team consisted of a certified nurse-midwife (CNM), a Certified Child Life Specialist, a maternal fetal medicine physician, a social worker, and a Spanish interpreter, with additional services consulted as needed. Between 2017 and 2020, this team grew to include 8 CNMs and provided care to 76 young adolescents ages 14 and younger. OUTCOMES: Of the young adolescents who attended prenatal visits with the Adolescent Prenatal Care Team at Parkland, 87% presented to Parkland for birth. Eighteen percent had pregnancy-induced hypertension or eclampsia. Only 7% of adolescents in the program gave birth prior to 37 weeks. Seventy-four percent had vaginal births. Sixty percent of the adolescents attended known postpartum visits. DISCUSSION: In contrast to most studies, this Adolescent Care Team did not find a high rate of premature birth in early adolescents. Further work by this team is needed to compare the data obtained during this period with data on similar adolescents who have given birth at Parkland in prior years. In addition, comparing outcomes of early adolescents with those aged 15 to 19, who were not included in the Adolescent Care Team, will help to understand the impact that such a team or similar intervention might have on this vulnerable population.

An adaptive teosinte mexicana introgression modulates phosphatidylcholine levels and is associated with maize flowering time.

Native Americans domesticated maize (Zea mays ssp. mays) from lowland teosinte parviglumis (Zea mays ssp. parviglumis) in the warm Mexican southwest and brought it to the highlands of Mexico and South America where it was exposed to lower temperatures that imposed strong selection on flowering time. Phospholipids are important metabolites in plant responses to low-temperature and phosphorus availability and have been suggested to influence flowering time. Here, we combined linkage mapping with genome scans to identify High PhosphatidylCholine 1 (HPC1), a gene that encodes a phospholipase A1 enzyme, as a major driver of phospholipid variation in highland maize. Common garden experiments demonstrated strong genotype-by-environment interactions associated with variation at HPC1, with the highland HPC1 allele leading to higher fitness in highlands, possibly by hastening flowering. The highland maize HPC1 variant resulted in impaired function of the encoded protein due to a polymorphism in a highly conserved sequence. A meta-analysis across HPC1 orthologs indicated a strong association between the identity of the amino acid at this position and optimal growth in prokaryotes. Mutagenesis of HPC1 via genome editing validated its role in regulating phospholipid metabolism. Finally, we showed that the highland HPC1 allele entered cultivated maize by introgression from the wild highland teosinte Zea mays ssp. mexicana and has been maintained in maize breeding lines from the Northern United States, Canada, and Europe. Thus, HPC1 introgressed from teosinte mexicana underlies a large metabolic QTL that modulates phosphatidylcholine levels and has an adaptive effect at least in part via induction of early flowering time.