Protocol for a Study Investigating Context-Specific Sedentary Behaviors and Cardiometabolic Health in College-Based Young Adults (CONTEXT-SB).

Background Sedentary behavior (SB) is detrimental to cardiometabolic disease (CMD) risk, which can begin in young adulthood. To devise effective SB-CMD interventions in young adults, it is important to understand which context-specific sedentary behaviors (CS-SB) are most detrimental for CMD risk, the lifestyle behaviors that co-exist with CS-SBs, and the socioecological predictors of CS-SB. Methods This longitudinal observational study will recruit 500 college-aged (18-24 years) individuals. Two laboratory visits will occur, spaced 12 months apart, where a composite CMD risk score (e.g., arterial stiffness, metabolic and inflammatory biomarkers, heart rate variability, and body composition) will be calculated, and questionnaires to measure lifestyle behaviors and different levels of the socioecological model will be administered. After each visit, total SB (activPAL) and CS-SB (television, transportation, academic/ occupational, leisure computer, "other"; ecological momentary assessment) will be measured across seven days. Discussion It is hypothesized that certain CS-SB will show stronger associations with CMD risk, compared to T-SB, even after accounting for coexisting lifestyle behaviors. It is expected that a range of intra-individual, inter-individual, and physical environment socioecological factors will predict CS-SB. The findings from this study will support the development of an evidence-based, multi-level intervention to target SB reduction and mitigate CMD risk in CBYA.

Pre-post-evaluation of a dementia-specific advance care planning toolkit for Japanese primary care clinicians.

BACKGROUND: The population of people living with dementia (PLwD) continues to grow in Japan where advance care planning (ACP) for PLwD is relatively new. Our aim was to evaluate the feasibility and cultural acceptability of a dementia-specific ACP communication skills toolkit for Japanese primary care clinicians. METHODS: We delivered 13 training sessions in primary care clinics across central Japan and conducted a post-training survey to assess whether the toolkit increased confidence in dementia-specific ACP communication skills and the acceptability of the toolkit with the following four statements: (1) The language in the sessions was clear, (2) The sessions took an appropriate amount of time to complete, (3) The design of the sessions was an effective educational method, and (4) The sessions were culturally appropriate for communication with Japanese patients with dementia and their family members. We asked participants to respond using a 5-point Likert scale from strongly agree to strongly disagree. RESULTS: All participants were Japanese and included 80 physicians (mean age 39.8 years), 33 nurses (mean age 45.7 years), and 58 other participants (mean age 42.9 years), who were 30.0%, 87.9%, and 55.2% female, respectively. Most participants practiced in rural settings. In pre- post-comparisons, participant confidence increased in determining capacity, understanding dementia prognosis, goals of care, eliciting surrogates, recommending self-care practices to families, and leading family meetings (all p < 0.001). Most participants strongly agreed or agreed that the toolkit was an effective method (96.9%), took an appropriate amount of time (94.5%), contained clear language (89.8%), and was culturally appropriate (73.6%). CONCLUSIONS: Dementia-specific ACP communication skills toolkit can be delivered in Japan. Japanese primary care clinicians generally felt the dementia-specific ACP toolkit increased their confidence in ACP communication skills and was acceptable. The language, time, and design were well received, though further work is needed to improve the cultural appropriateness of the toolkit.

The utility of home blood pressure load in predicting average self-measured blood pressure.

OBJECTIVES: Average values for self-measured blood pressure (SMBP) more accurately reflect a patient's risk of cardiovascular disease than do office measurements. Oftentimes, however, patients provide lists of individual home blood pressure (BP) measurements, and average values cannot be computed within the time constraints of a clinic visit. In contrast, the home BP load - defined as the proportion of BP values greater than a partition value (e.g., 130 mmHg) - can be easily calculated. We examined the utility of the BP load in predicting the mean SMBP and confirming elevated SMBP. METHODS: Four hundred twenty untreated adults at least 30 years of age acquired SMBP data twice in the morning and twice in the evening over 10 days. The 'true' SMBP was defined as the mean of these 40 determinations. RESULTS: Using all 10 days of BP data and a systolic BP threshold of 130 mmHg, the average SMBP associated with a home BP load of 0.50 was 130 mmHg, with a 95% prediction interval of 126-133 mmHg. True systolic SMBP was approximately 6 mmHg lower and higher at home BP loads of 0.25 and 0.75, respectively. There was a 90% probability that the true systolic SMBP was greater than 130 mmHg if the systolic home BP load was at least 0.60. Corresponding values for 3 days and 1 day of SMBP were at least 0.68 and at least 0.84, respectively. CONCLUSION: Our analysis demonstrates that the home BP load can be used to estimate the average BP acquired on home monitoring and confirm elevated SMBP.

Cultural Connection and Well-being for American Indian Adolescents.

American Indian and Alaska Native (AI/AN) adolescents face health disparities resulting from historical traumas. There is a paucity of research focusing on mental health in AI/AN adolescents or the relationship between cultural connection and health. This project assesses the relationship between cultural identity and markers of mental health and well-being for AI/AN adolescents. Adolescents 12 to 18 years old from the Lumbee Tribe of North Carolina participated in this mixed-methods study. Phase 1, discussed in this manuscript, involved surveys using validated instruments to assess cultural connection and markers of mental health and well-being. Characteristics of the 122 AI/AN youth who completed the survey included: mean age 14.9 years (SD = 2.0); 61% (n = 75) assigned female at birth; 56% (n = 70) identified as female; and 4.1% (n = 5) identified as non-binary. Mean tribal affiliation (TA) and ethnic identity (EI) scores suggest strong cultural connection (TA: M = 3.1/5, SD = 0.6; EI: M = 3.4/5, SD = 0.9). Sleep quality (M = 2.63/5) and positive stress management (M = 2.06/5) were low. Bivariate and logistic regression demonstrated moderate positive correlations between EI and friendship, EI and emotional support, TA and friendship, and TA and emotional support. AI/AN adolescents in this sample have a moderate-strong connection with Native culture, marked by ethnic identity and tribal affiliation, and positive markers of mental health and well-being. Data from this study may be used for policy formulation to promote increased funding and programming addressing mental health for AI/AN youth.

A Multi-state Non-Markov Framework to Estimate Progression of Chronic Disease.

In chronic disease epidemiology, investigation of disease etiology has largely focused on one single endpoint, and progression of chronic disease as a multi-state process is understudied, representing a knowledge gap. Most of existing multi-state regression models require Markov assumption and are unsuitable to estimate progression of chronic diseases that is largely non-memoryless. We propose a new non-Markov framework that allows past states to affect transition rates of current states. The key innovation is that we convert a non-Markov to Markov process by dividing disease states into substates through conditioning on past disease history. Specifically, we apply cause-specific Cox models (CSC) including past states as covariates to obtain transition rates (TR) of substates, which were used to obtain transition probabilities (TP) and state occupational probabilities (SOP) of substates. We applied our model to describe progression of coronary heart disease (CHD) in the ARIC study, where CHD was modeled in healthy, in risk, CHD, heart failure, and mortality states. We presented transition rates, transition probabilities, and state occupational probabilities between states from age 45 to 95 years. In summary, the significance of our framework lies in that transition parameters between disease substates may shed light on new mechanistic insight of chronic disease and may provide more accurate description of non-Markov process than Markov regression models. Our method has potential of wide application in chronic disease epidemiology.

Micro-heterogeneity of transmission shapes submicroscopic malaria carriage in coastal Tanzania.

BACKGROUND: Asymptomatic carriage of malaria parasites persists even as malaria transmission declines. Low density infections are often submicroscopic, not detected by rapid diagnostic tests (RDTs) or microscopy, but detectable by PCR. METHODS: To characterize submicroscopic Plasmodium falciparum carriage in an area of declining malaria transmission, asymptomatic persons >5 years of age in rural Bagamoyo District, Tanzania, were screened using RDT, microscopy, and PCR. We investigated the size of the submicroscopic reservoir of infection across villages, determined factors associated with submicroscopic carriage, and assessed the natural history of submicroscopic malaria over four weeks. RESULTS: Among 6,076 participants, P. falciparum prevalence by RDT, microscopy, and PCR was 9%, 9%, and 28%, respectively, with roughly two-thirds of PCR-positive individuals harboring submicroscopic infection. Adult status, female gender, dry season months, screened windows, and bednet use were associated with submicroscopic carriage. Among 15 villages encompassing 80% of participants, the proportion of submicroscopic carriers increased with decreasing village-level malaria prevalence. Over four weeks, 23% (61/266) of submicroscopic carriers became RDT-positive, with half exhibiting symptoms, while half (133/266) were no longer parasitemic at the end of four weeks. Progression to RDT-positive patent malaria occurred more frequently in villages with higher malaria prevalence. CONCLUSIONS: Micro-heterogeneity in transmission observed at the village level appears to impact both the size of the submicroscopic reservoir and the likelihood of submicroscopic carriers developing patent malaria in coastal Tanzania.

Optimizing calibration of modern skeletal maturity systems.

Purpose: Greulich and Pyle is the most used system to estimate skeletal maturity but has significant drawbacks, prompting the development of newer skeletal maturity systems, such as the modified Fels skeletal maturity systems based on knee radiographs. To create a new skeletal maturity system, an outcome variable, termed a "skeletal maturity standard," must be selected for calibration of the system. Peak height velocity and 90% of final height are both considered reasonable skeletal maturity standards for skeletal maturity system development. We sought to answer two questions: (1) Does a skeletal maturity system developed using 90% of final height estimate skeletal age as well as it would if it was instead developed using peak height velocity? (2) Does a skeletal maturity system developed using 90% of final height perform as well in lower extremity length prediction as it would if it was instead developed using peak height velocity? Methods: The modified Fels knee skeletal maturity system was recalibrated based on 90% of final height and peak height velocity skeletal maturity standards. These models were applied to 133 serially obtained, peripubertal antero-posterior knee radiographs collected from 38 subjects. Each model was used to estimate the skeletal age of each radiograph. Skeletal age estimates were also used to predict each patient's ultimate femoral and tibial length using the White-Menelaus method. Results: The skeletal maturity system calibrated with 90% of final height produced more accurate skeletal age estimates than the same skeletal maturity system calibrated with peak height velocity (p < 0.05). The 90% of final height and peak height velocity models made similar femoral and tibial length predictions (p > 0.05). Conclusion: Using the 90% of final height skeletal maturity standard allows for simpler skeletal maturity system development than peak height velocity with potentially more accuracy.

Who chooses "healthy" meals? An analysis of lunchtime meal quality in a workplace cafeteria.

BACKGROUND: The workplace can play an important role in shaping the eating behaviors of U.S. adults. Unfortunately, foods obtained in the workplace tend to be low in nutritional quality. Questions remain about the best way to approach the promotion of healthy food purchases among employees and to what extent health promotion activities should be tailored to the demographic characteristics of the employees. The purpose of this study was to (1) assess the nutritional quality of lunchtime meal purchases by employees in cafeterias of a large organization, (2) examine associations between lunchtime meal quality selection and the demographic characteristics of employees, and (3) determine the healthfulness of foods and beverages offered in the cafeterias of this organization. METHODS: A cross-sectional analysis was conducted using secondary data from a food labeling study implemented in three worksite cafeterias. Demographic data was collected via surveys and meal data was collected using a photo capture system for 378 participants. The Healthy Eating Index 2015 (HEI-2015) was used to determine meal quality and a total score for the menu of options available in the cafeterias during the study period. Summary statistics were generated, and the analysis of variance (ANOVA) was used to compare the HEI-2015 scores between groups. RESULTS: The mean HEI-2015 total score for the menu items offered (n = 1,229) in the cafeteria during the study period was 63.1 (SD = 1.83). The mean HEI-2015 score for individual lunchtime meal observations (n = 378) was 47.1 (SD = 6.8). In general, HEI-2015 total scores were higher for non-smokers, individuals who self-identified as Asian, had higher physical activity levels, scored higher on numeracy and literacy assessments, and reported higher education levels, incomes, and health status. CONCLUSIONS: The overall HEI-2015 scores indicate that the menu of options offered in the cafeterias and individual meal selections did not align with the Dietary Guidelines for Americans, and there were significant associations between average lunchtime meal quality scores and several demographic characteristics. These results suggest that healthy eating promotion activities in workplaces may need to be tailored to the demographic characteristics of the employees, and efforts to improve the food environment in the workplace could improve meal quality for all employees.

Long-Acting Reversible Contraception Initiation Among Adolescents After an American Academy of Pediatrics Policy Statement.

This cross-sectional study compares monthly rates of long-acting reversible contraception (LARC) insertions among adolescents before and after an American Academy of Pediatrics (AAP) policy statement recommending LARC for this age group.

Situs Ambiguus Is Associated With Adverse Clinical Outcomes in Children With Primary Ciliary Dyskinesia.

BACKGROUND: Primary ciliary dyskinesia (PCD) is a rare disorder of motile cilia associated with situs abnormalities. At least 12% of patients with PCD have situs ambiguus (SA), including organ laterality defects falling outside normal arrangement (situs solitus [SS]) or mirror image inversion (situs inversus totalis [SIT]). RESEARCH QUESTION: Do patients with PCD and SA achieve worse clinical outcomes compared with those with SS or SIT? STUDY DESIGN AND METHODS: This cross-sectional, multicenter study evaluated participants aged 21 years or younger with PCD. Participants were classified as having SA, including heterotaxy, or not having SA (SS or SIT). Markers of disease severity were compared between situs groups, adjusting for age at enrollment and severe CCDC39 or CCDC40 genotype, using generalized linear models and logistic and Poisson regression. RESULTS: In 397 participants with PCD (mean age, 8.4 years; range, 0.1-21), 42 patients were classified as having SA, including 16 patients (38%) with complex cardiovascular malformations or atrial isomerism, 13 patients (31%) with simple CVM, and 13 patients (31%) without cardiovascular malformations. Of these, 15 patients (36%) underwent cardiac surgery, 24 patients (57%) showed an anatomic spleen abnormality, and seven patients (17%) showed both. The remaining 355 participants did not have SA, including 152 with SIT and 203 with SS. Overall, 70 participants (17%) harbored the severe CCDC39 or CCDC40 genotype. Compared with participants without SA, those with SA showed lower median BMI z scores (P = .03), lower FVC z scores (P = .01), and more hospitalizations and IV antibiotic courses for acute respiratory infections during the 5 years before enrollment (P < .01). Participants with cardiovascular malformations requiring surgery or with anatomic spleen abnormalities showed lower median BMI z scores and more hospitalizations and IV therapies for respiratory illnesses compared with participants without SA. INTERPRETATION: Children with PCD and SA achieve worse nutritional and pulmonary outcomes with more hospitalizations for acute respiratory illnesses than those with SS or SIT combined. Poor nutrition and increased hospitalizations for respiratory infections in participants with SA and PCD are associated with cardiovascular malformations requiring cardiac surgery, splenic anomalies, or both. TRIAL REGISTRY: ClinicalTrials.gov; Nos.: NCT02389049 and NCT00323167; URL: www. CLINICALTRIALS: gov.

Real-time PCR detection of mixed Plasmodium ovale curtisi and wallikeri infections in human and mosquito hosts.

Plasmodium ovale curtisi (Poc) and Plasmodium ovale wallikeri (Pow) represent distinct non-recombining Plasmodium species that are increasing in prevalence in sub-Saharan Africa. Though they circulate sympatrically, co-infection within human and mosquito hosts has rarely been described. Separate 18S rRNA real-time PCR assays that detect Poc and Pow were modified to allow species determination in parallel under identical cycling conditions. The lower limit of detection was 0.6 plasmid copies/µL (95% CI 0.4-1.6) for Poc and 4.5 plasmid copies/µL (95% CI 2.7-18) for Pow, or 0.1 and 0.8 parasites/µL, respectively, assuming 6 copies of 18s rRNA per genome. However, the assays showed cross-reactivity at concentrations greater than 103 plasmid copies/µL (roughly 200 parasites/µL). Mock mixtures were used to establish criteria for classifying mixed Poc/Pow infections that prevented false-positive detection while maintaining sensitive detection of the minority ovale species down to 100 copies/µL (<1 parasite/µL). When the modified real-time PCR assays were applied to field-collected blood samples from Tanzania and Cameroon, species identification by real-time PCR was concordant with nested PCR in 19 samples, but additionally detected two mixed Poc/Pow infections where nested PCR detected a single Po species. When real-time PCR was applied to oocyst-positive Anopheles midguts saved from mosquitoes fed on P. ovale-infected persons, mixed Poc/Pow infections were detected in 11/14 (79%). Based on these results, 8/9 P. ovale carriers transmitted both P. ovale species to mosquitoes, though both Po species could only be detected in the blood of two carriers. The described real-time PCR approach can be used to identify the natural occurrence of mixed Poc/Pow infections in human and mosquito hosts and reveals that such co-infections and co-transmission are likely more common than appreciated.

In focus: perplexing increase of urinary stone disease in children, adolescent and young adult women and its economic impact.

Background: Urinary stone disease (USD) historically has affected older men, but studies suggest recent increases in women, leading to a near identical sex incidence ratio. USD incidence has doubled every 10 years, with disproportionate increases amongst children, adolescent, and young adult (AYA) women. USD stone composition in women is frequently apatite (calcium phosphate), which forms in a higher urine pH, low urinary citrate, and an abundance of urinary uric acid, while men produce more calcium oxalate stones. The reasons for this epidemiological trend are unknown. Methods: This perspective presents the extent of USD with data from a Canadian Province and a North American institution, explanations for these findings and offers potential solutions to decrease this trend. We describe the economic impact of USD. Findings: There was a significant increase of 46% in overall surgical interventions for USD in Ontario. The incidence rose from 47.0/100,000 in 2002 to 68.7/100,000 population in 2016. In a single United States institution, the overall USD annual unique patient count rose from 10,612 to 17,706 from 2015 to 2019, and the proportion of women with USD was much higher than expected. In the 10-17-year-old patients, 50.1% were girls; with 57.5% in the 18-34 age group and 53.6% in the 35-44 age group. The roles of obesity, diet, hormones, environmental factors, infections, and antibiotics, as well as the economic impact, are discussed. Interpretation: We confirm the significant increase in USD among women. We offer potential explanations for this sex disparity, including microbiological and pathophysiological aspects. We also outline innovative solutions - that may require steps beyond typical preventive and treatment recommendations.

Decision Factors for Glaucoma Suspects and Ocular Hypertensive Treatment at an Academic Center.

Aims and background: Practice guidelines assert that high-risk glaucoma suspects should be treated. Yet, there is ambiguity regarding what constitutes a high enough risk for treatment. The purpose of this study was to determine which factors contribute to the decision to treat glaucoma suspects and ocular hypertensive patients in an academic ophthalmology practice. Materials and methods: Retrospective cohort study of glaucoma suspects or ocular hypertensives at an academic ophthalmology practice from 2014 to 2020. Demographics, comorbidities, intraocular pressure (IOP), optical coherence tomography (OCT) findings, and visual field measurements were compared between treated and untreated patients. A multivariable logistic regression model assessed predictors of glaucoma suspected treatment. Results: Of the 388 patients included, 311 (80%) were untreated, and 77 (20%) were treated. There was no statistical difference in age, race/ethnicity, family history of glaucoma, central corneal thickness (CCT), or any visual field parameters between the two groups. Treated glaucoma suspects had higher IOP, thinner retinal nerve fiber layers (RNFL), more RNFL asymmetry, thinner ganglion cell-inner plexiform layers (GCIPL), and a higher prevalence of optic disc drusen, disc hemorrhage, ocular trauma, and proliferative diabetic retinopathy (PDR) (p < 0.05 for all). In the multivariable model, elevated IOP {odds ratio [OR] 1.16 [95% confidence interval (CI) 1.04-1.30], p = 0.008}, yellow temporal [5.76 (1.80-18.40), p = 0.003] and superior [3.18 (1.01-10.0), p = 0.05] RNFL quadrants, and a history of optic disc drusen [8.77 (1.96-39.34), p = 0.005] were significant predictors of glaucoma suspect treatment. Conclusion: Higher IOP, RNFL thinning, and optic disc drusen were the strongest factors in the decision to treat a glaucoma suspect or ocular hypertensive patient. RNFL asymmetry, GCIPL thinning, and ocular comorbidities may also factor into treatment decisions. Clinical significance: Understanding the clinical characteristics that prompt glaucoma suspect treatment helps further define glaucoma suspect disease status and inform when treatment should be initiated. How to cite this article: Ciociola EC, Anderson A, Jiang H, et al. Decision Factors for Glaucoma Suspects and Ocular Hypertensive Treatment at an Academic Center. J Curr Glaucoma Pract 2023;17(3):157-165.

Design of a dual randomized trial in a type 2 hybrid effectiveness-implementation study.

BACKGROUND: Dual randomized controlled trials (DRCT) are type 2 hybrid studies that include two randomized trials: one testing implementation strategies and one testing an intervention. We argue that this study design offers efficiency by providing rigorous investigation of both implementation and intervention in one study and has potential to accelerate generation of the evidence needed to translate interventions that work into real-world practice. Nevertheless, studies using this design are rare in the literature. MAIN TEXT: We construct a paradigm that breaks down the components of the DRCT and provide a step-by-step explanation of features of the design and recommendations for use. A clear distinction is made between the dual strands that test the implementation versus the intervention, and a minimum of three randomized arms is advocated. We suggest an active treatment arm that includes both the implementation strategy and intervention that are hypothesized to be superior. We suggest two comparison/control arms: one to test the implementation strategy and the second to test the intervention. Further, we recommend selection criteria for the two control arms that place emphasis on maximizing the utility of the study design to advance public health practice. CONCLUSIONS: On the surface, the design of a DRCT can appear simple, but actual application is complex. We believe it is that complexity that has limited its use in the literature. We hope that this paper will give both implementation scientists and trialists who are not familiar with implementation science a better understanding of the DRCT design and encouragement to use it.

Histologic characterization of primary ciliary dyskinesia chronic rhinosinusitis.

KEY POINTS: We present the largest cohort of structured histopathology reports on primary ciliary dyskinesia-related chronic rhinosinusitis (PCD-CRS). Despite endoscopic differences, PCD-CRS and cystic fibrosis-related chronic rhinosinusitis (CF-CRS) had similar structured histopathology reports. Compared to healthy patients and those with idiopathic chronic rhinosinusitis without nasal polyps, patients with PCD-CRS had an increased neutrophil count.

Radiographic and Patient-Reported Outcomes of a Low-Cost Modified Lapidus Bunion Correction Technique.

Background: The modified Lapidus (ML) is a powerful procedure for correction of hallux valgus (HV) with emerging techniques. Studies considering patient-reported outcomes, radiographic measures, complications, and implant costs are currently limited. Methods: Retrospective cohort with prospectively collected Patient Reported Outcome Information System Physical Function (PROMIS-PF) Computerized Adaptive Test (CAT) scores, radiographic parameters (intermetatarsal angle, IMA; hallux valgus angle, HVA; and tibial sesamoid position, TSP), complications, and total operative time and implant costs were reviewed from 2014 to 2019. Results: Seventy-three feet (68 patients) underwent bunion correction by ML with lag-screw fixation. Median age was 55.8 years (IQR 45.6, 53.9), 4 of 73 (5.5%) were male, 11 of 73 (15.1%) were smokers, and 15 of 73 (20.6%) were diabetic (median HbA1c 6.4% [IQR 6.0, 7.4], none insulin dependent, 5 of 15 with neuropathy). Complications included 6 of 73 (8.2%) wound issues resolved with topical or oral treatment, 9 of 73 (12.3%) painful or broken hardware requiring hardware removal. Two of 73 (2.7%) had persistent pain despite union. One of 73 (1.4%) was overcorrected and required first MTP arthrodesis. Of 3 nonunions (2.7%), 1 resolved with corrected hypothyroidism, 1 was asymptomatic and required no treatment, 1 had a hallux valgus recurrence and sought revision surgery elsewhere. Preoperative radiographic angles were HVA 35 degrees, IMA 14 degrees which improved at final postoperative follow up to HVA 10 degrees, IMA 6 degrees. Tibial sesamoid position improved from 6.05 ± 1.00 to 2.22 ± 1.38. Thirty-two patients had preoperative and 42 had 1-year postoperative outcomes. PROMIS-PF (51% collection rate) was 43 (IQR 37,52) preoperatively, 37 (31, 39) at 6 weeks, 46 (42, 51) at 3 months, and 49 (41, 53) at >360 days postoperatively. The drop in PROMIS-PF between preoperative and 6 weeks and the rise from 6 weeks to 3 months were statistically significant. Pre- and postoperative PROMIS-PF scores were not significantly different. Implant cost averaged US$146. Discussion/Conclusion: We report low complication rates and costs with high patient postoperative functional and radiographic outcomes. PROMIS-PF decreased acutely postoperatively but recovered and maintained high levels by 3 months postoperatively. Level of Evidence: Level IV, case series.

Neonatal Outcomes after Medications for Opioid Use Disorder during Pregnancy in a State Women's Prison Facility, 2016-2019.

OBJECTIVE: Although medications for opioid use disorder improve both maternal and neonatal outcomes, little is known about opioid-exposed infants born during episodes of incarceration. The study sought to examine birth outcomes for infants born with opioid exposure during perinatal incarceration. METHODS: Participants were identified from clinic rosters in a Southeastern women's prison (2016-2019). Included infants born to pregnant people with opioid use disorder incarcerated in the study facility at the time of delivery. We abstracted hospital length of stay, neonatal opioid withdrawal syndrome (NOWS) severity, and discharge plan from hospital records and report descriptive statistics, analysis of variance F tests, and chi-square tests to compare outcomes by opioid exposure type. RESULTS: There were 125 infants born after exposure to methadone (n = 34), buprenorphine (n = 15), oxycodone (n = 22), or no opioid medication (n = 54) during prenatal incarceration. Most infants exposed to methadone or buprenorphine had difficulty with eating, sleeping, or consoling (97% and 80%), and 59% and 47% were treated with medication for NOWS, respectively. The majority with prenatal opioid exposure required intervention for NOWS symptoms after their birthing parent was discharged to the prison. The average hospital length of stay was different for infants with no opioid, methadone, buprenorphine, and oxycodone exposure during incarceration (4, 15, 12, and 9 days, respectively, P < 0.001). CONCLUSIONS: Neonatal hospitalization experiences of infants with perinatal opioid exposures during maternal incarceration mirror those of similarly exposed infants born outside the context of incarceration, except for hospital length of stay. Consideration of avoiding separation of the parent-infant dyad may be needed to improve outcomes for these infants.

RNA-binding deficient TDP-43 drives cognitive decline in a mouse model of TDP-43 proteinopathy.

TDP-43 proteinopathies including frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) are neurodegenerative disorders characterized by aggregation and mislocalization of the nucleic acid-binding protein TDP-43 and subsequent neuronal dysfunction. Here, we developed endogenous models of sporadic TDP-43 proteinopathy based on the principle that disease-associated TDP-43 acetylation at lysine 145 (K145) alters TDP-43 conformation, impairs RNA-binding capacity, and induces downstream mis-regulation of target genes. Expression of acetylation-mimic TDP-43K145Q resulted in stress-induced nuclear TDP-43 foci and loss of TDP-43 function in primary mouse and human-induced pluripotent stem cell (hiPSC)-derived cortical neurons. Mice harboring the TDP-43K145Q mutation recapitulated key hallmarks of FTLD, including progressive TDP-43 phosphorylation and insolubility, TDP-43 mis-localization, transcriptomic and splicing alterations, and cognitive dysfunction. Our study supports a model in which TDP-43 acetylation drives neuronal dysfunction and cognitive decline through aberrant splicing and transcription of critical genes that regulate synaptic plasticity and stress response signaling. The neurodegenerative cascade initiated by TDP-43 acetylation recapitulates many aspects of human FTLD and provides a new paradigm to further interrogate TDP-43 proteinopathies.

Micro-heterogeneity of transmission shapes the submicroscopic malaria reservoir in coastal Tanzania.

Background: Asymptomatic malaria may be patent (visible by microscopy) and detectable by rapid malaria diagnostic tests (RDTs), or it may be submicroscopic and only detectable by polymerase chain reaction (PCR). Methods: To characterize the submicroscopic reservoir in an area of declining malaria transmission, asymptomatic persons >5 years of age in Bagamoyo District, Tanzania, were screened using RDT, microscopy, and PCR. We investigated the size of the submicroscopic reservoir across villages, determined factors associated with submicroscopic parasitemia, and assessed the natural history of submicroscopic malaria over four weeks. Results: Among 6,076 participants, Plasmodium falciparum prevalence by RDT, microscopy, and PCR was 9%, 9%, and 28%, respectively, with roughly two-thirds of PCR-positive individuals harboring submicroscopic infection. Adult status, female gender, dry season months, screened windows, and bednet use were associated with submicroscopic carriage. Among 15 villages encompassing 80% of participants, the proportion of submicroscopic carriers increased with decreasing village-level malaria prevalence. Over four weeks, 23% (61/266) of submicroscopic carriers became RDT-positive and were treated, with half exhibiting symptoms. This occurred more frequently in villages with higher malaria prevalence. Conclusions: Micro-heterogeneity in transmission impacts the size of the submicroscopic reservoir and the likelihood of submicroscopic carriers developing patent malaria in coastal Tanzania.