Applications of Flow Cytometry in Diagnosis and Evaluation of Red Blood Cell Disorders.

Clinical flow cytometry plays a vital role in the diagnosis and monitoring of various red blood cell disorders. The high throughput, precision, and automation potential of this technique allows for cost-effective and timely analysis compared to older and more manual test methods. Flow cytometric analysis serves as the gold standard diagnostic method for multiple hematological disorders, especially in clinical scenarios where an assay needs to have high sensitivity, high specificity, and a short turnaround time. In this review, we discuss the role of flow cytometric analysis in paroxysmal nocturnal hemoglobinuria, fetal-maternal hemorrhage, and hereditary spherocytosis.

Transcriptional regulation of the postnatal cardiac conduction system heterogeneity.

The cardiac conduction system (CCS) is a network of specialized cardiomyocytes that coordinates electrical impulse generation and propagation for synchronized heart contractions. Although the components of the CCS, including the sinoatrial node, atrioventricular node, His bundle, bundle branches, and Purkinje fibers, were anatomically discovered more than 100 years ago, their molecular constituents and regulatory mechanisms remain incompletely understood. Here, we demonstrate the transcriptomic landscape of the postnatal mouse CCS at a single-cell resolution with spatial information. Integration of single-cell and spatial transcriptomics uncover region-specific markers and zonation patterns of expression. Network inference shows heterogeneous gene regulatory networks across the CCS. Notably, region-specific gene regulation is recapitulated in vitro using neonatal mouse atrial and ventricular myocytes overexpressing CCS-specific transcription factors, Tbx3 and/or Irx3. This finding is supported by ATAC-seq of different CCS regions, Tbx3 ChIP-seq, and Irx motifs. Overall, this study provides comprehensive molecular profiles of the postnatal CCS and elucidates gene regulatory mechanisms contributing to its heterogeneity.

CHARACTERIZATION OF VAULT WITH TWO MODELS OF POSTERIOR CHAMBER PHAKIC INTRAOCULAR LENSES.

PURPOSE: To evaluate and compare the dynamic vault range (DVR) as well as the asymmetry of the vault during a 3-month follow-up after the implantation of two posterior chamber phakic intraocular lenses (pIOLs). SETTING: Aver Clinic, Madrid, Spain. DESIGN: Prospective comparative study. METHODS: One hundred and nineteen eyes (65 patients) that underwent refractive surgical correction with implantation of one of two distinct pIOLs were enrolled: Eyecryl Phakic from Biotech Vision Care (Eyecryl group, 72 eyes) and Evo Visian Implantable Contact Lens from Staar Surgical (ICL group, 47 eyes). Besides evaluation of visual acuity, refraction, and ocular integrity, the pIOL vault was measured centrally and at 2 mm nasally and temporally as well as the DVR from photopic (50 lux) to mesopic (10 lux) illuminations conditions. RESULTS: No significant differences were found between pIOL groups in visual and refractive outcomes (p≥0.454). No significant differences between groups were found in central (523.72±168.4 vs. 494.16±156.7 µm, p=0.248) and temporal vault (499.43±155.8 vs. 431.28±150.5 µm, p=0.067). However, nasal vault was significantly lower in ICL group (465.6±149.1 vs. 375.4±144.0 µm, p=0.045). A trend to a larger DVR was observed in the ICL group, although differences between groups did not reach statistical significance (54.00±36.39 vs. 86.5±57.9 µm p=0.070). The pIOL diameter only correlated significantly with vault measurements in ICL group (r≥0.650, p<0.001). CONCLUSIONS: The Eyecryl pIOL shows more symmetric vaults and a trend to fewer light-induced changes in the central vault compared to the ICL pIOL. The clinical relevance of this finding should be investigated further.

'It's a job to be done'. Managing polypharmacy at home: A qualitative interview study exploring the experiences of older people living with frailty.

INTRODUCTION: Many older people live with both multiple long-term conditions and frailty; thus, they manage complex medicines regimens and are at heightened risk of the consequences of medicines errors. Research to enhance how people manage medicines has focused on adherence to regimens rather than on the wider skills necessary to safely manage medicines, and the older population living with frailty and managing multiple medicines at home has been under-explored. This study, therefore, examines in depth how older people with mild to moderate frailty manage their polypharmacy regimens at home. METHODS: Between June 2021 and February 2022, 32 patients aged 65 years or older with mild or moderate frailty and taking five or more medicines were recruited from 10 medical practices in the North of England, United Kingdom, and the CARE 75+ research cohort. Semi-structured interviews were conducted face to face, by telephone or online. The interviews were recorded, transcribed verbatim and analysed using reflexive thematic analysis. FINDINGS: Five themes were developed: (1) Managing many medicines is a skilled job I didn't apply for; (2) Medicines keep me going, but what happened to my life?; (3) Managing medicines in an unclear system; (4) Support with medicines that makes my work easier; and (5) My medicines are familiar to me-there is nothing else I need (or want) to know. While navigating fragmented care, patients were expected to fit new medicines routines into their lives and keep on top of their medicines supply. Sometimes, they felt let down by a system that created new obstacles instead of supporting their complex daily work. CONCLUSION: Frail older patients, who are at heightened risk of the impact of medicines errors, are expected to perform complex work to safely self-manage multiple medicines at home. Such a workload needs to be acknowledged, and more needs to be done to prepare people in order to avoid harm from medicines. PATIENT AND PUBLIC INVOLVEMENT: An older person managing multiple medicines at home was a core member of the research team. An advisory group of older patients and family members advised the study and was involved in the first stages of data analysis. This influenced how data were coded and themes shaped.

Programmable acoustic modular microrobots.

The field of microrobotics has emerged as a promising area of research with significant applications in biomedicine, both in vitro and in vivo, such as targeted cargo delivery, microsurgery, and cellular manipulation. Microrobots actuated with multiple modalities have the potential for greater adaptability, robustness, and capability to perform various tasks. Modular units that can reconfigure into various shapes, create structures that may be difficult to fabricate as one whole unit, and be assembled on-site, could provide more versatility by assembly and disassembly of units on demand. Such multi-modal modular microrobots have the potential to address challenging applications. Here, we present a biocompatible cylindrical microrobot with a dome-shaped cavity. The microrobot is actuated by both magnetic and acoustic fields and forms modular microstructures of various shapes. We demonstrate the use of these microrobots for cellular manipulation by creating patterns on a surface. Supplementary Information: The online version contains supplementary material available at 10.1007/s12213-024-00175-y.

Magnetometry in a diamond anvil cell using nitrogen vacancy centers in a nanodiamond ensemble.

The emerging field of optical magnetometry utilizing negative-charged nitrogen vacancy (NV-) centers provides a highly sensitive lab bench technique for spatially resolved physical property measurements. Their implementation in high pressure diamond anvil cell (DAC) environments will become common as other techniques are often limited due to the spatial constraints of the sample chamber. Apparatus and techniques are described here permitting for more general use of magnetic field measurements inside a DAC using continuous wave optical detected magnetic resonance in NV- centers in a layer of nanodiamonds. A microstrip antenna delivers a uniform microwave field to the DAC and is compatible with simple metal gaskets, and the sensor layer of deposited nanodiamonds allows for simple determination of the magnetic field magnitude for B in the 1-100 G range. The ferromagnetic transition in iron at 18 GPa is measured with the apparatus, along with its hysteretic response.

Neural Changes after Vision Therapy in Convergence Insufficiency: A Systematic Review.

Objective: To investigate if the use of vision therapy (VT) in convergence insufficiency (CI) has a significant neural impact and how it correlates with the clinical changes occurring with this option of treatment. Methods: A systematic review of the scientific literature was carried out in the PubMed and Scopus databases, where all the scientific literature on the neural impact of VT in CI was analyzed. A total of 17 articles were initially found and a detailed analysis was carried out. After full-text reading, only four studies met the defined inclusion criteria. The following data from them were extracted: CI cases and controls, clinical and neural parameters evaluated, the neural response to VT observed, type of study, and VT performed. The quality of the studies was assessed using the GRADE tool. Results: Some neural changes have been reported after VT in CI with the use of functional magnetic resonance imaging (fMRI). Specifically, a modification of the functional activity of some brain areas (especially front fields, oculomotor vermis, and cerebellum) was found. However, contradictory findings in terms of the change in functional activity (increase or decrease) were found that might be associated to differences in fMRI protocols. In the GRADE analysis, serious concerns were found in the categories of risk of bias, inconsistency, indirectness, and imprecision, so the certainty of evidence for each outcome was very low. Conclusion: The research performed to this date does not allow confirming if there are neural changes occurring after vision therapy in patients with CI because the quality of the research performed on this issue is very low, with several methodological concerns.

Overcoming Barriers to Latino Participation in Alzheimer's Disease Research.

There is a critical need to increase Latino participation in research on Alzheimer's disease and related disorders (ADRD). Applying principles of community-based participatory research, we convened a community advisory board (CAB) to identify barriers and recommend strategies to increase participation of older Latinos in a longitudinal observational research study of ADRD at the Shiley-Marcos Alzheimer's Disease Research Center. Six major barriers were identified and programmatic changes to overcome them were implemented. Changes resulted in a nearly three-fold increase in the number of Latino individuals recruited, with the proportion of all newly recruited participants who were Latino increasing from 12.2% to 57.4%. Newer Latino recruits were more representative of the elderly Latino population in San Diego County than those recruited pre-CAB and remained highly agreeable to blood draw and neuroimaging, though less so to lumbar puncture and autopsy. Results demonstrate the value of CAB involvement in enhancing diversity in ADRD research.

Pulsed Vibro-Acoustic Analysis Technique for Monitoring Bone Health in Preterm Infants: A Pilot Study.

Despite advances in neonatal care, metabolic bone disease of prematurity (MBDP) remains a common problem in preterm infants. The development of non-invasive and affordable diagnostic approaches can be highly beneficial in the diagnosis and management of preterm infants at risk of MBDP. In this study, we present an ultrasound method called pulsed vibro-acoustic analysis to investigate the progression of bone mineralization in infants over time versus weight and postmenstrual age. The proposed pulsed vibro-acoustic analysis method is used to evaluate the vibrational characteristics of the bone. This method uses the acoustic radiation force of ultrasound to vibrate the bone. The generated acoustic waves are detected using a hydrophone placed on the skin over the tibia. The frequency of vibration and the speeds of received acoustic waves have information regarding the material property of the bone. We examined the feasibility of this method through an in vivo study consisting of 25 preterm and 10 full term infants. The pulsed vibro-acoustic data were acquired longitudinally in preterm infants with multiple visits and at a single visit in full term infants. Speed of sound and mean peak frequency of slow and fast sound waves recorded by hydrophone were used to analyze bone mineralization progress. Linear mixed model was used for statistical analysis in characterizing the mineralization progress in preterm infants compared to data from full term subjects. Significance changes in wave parameters (speed of sound and mean peak frequency) with respect to the postmenstrual age and weight in preterm infants were observed with p-values less than 0.05. Statistical significances in speed of sound measurement for both fast and slow waves were observed between preterm and full term infants, with p-values of <0.01 and 0.02, respectively. The results of this pilot study indicate the potential use of vibro-acoustic analysis for monitoring the progression of bone mineralization in preterm infants.

CT-guided online adaptive stereotactic body radiotherapy for pancreas ductal adenocarcinoma: Dosimetric and initial clinical experience.

Purpose/Objectives: Retrospective analysis suggests that dose escalation to a biologically effective dose of more than 70 Gy may improve overall survival in patients with pancreatic ductal adenocarcinoma (PDAC), but such treatments in practice are limited by proximity of organs at risk (OARs). We hypothesized that CT-guided online adaptive radiotherapy (OART) can account for interfraction movement of OARs and allow for safe delivery of ablative doses. Materials/Methods: This is a single institution retrospective analysis of patients with PDAC treated with OART on the Ethos platform (Varian Medical Systems, a Siemens Healthineers Company, Palo Alto). All patients were treated to 40 Gy in 5 fractions. PTV overlapping with a 5 mm planning risk volume expansion on the stomach, duodenum and bowel received 25 Gy. Initial treatment plans were created conventionally. For each fraction, PTV and OAR volumes were recontoured with AI assistance after initial cone beam CT (CBCT). The adapted plan was calculated, underwent QA, and then compared to the scheduled plan. A second CBCT was obtained prior to delivery of the selected plan. Total treatment time (first CBCT to end of radiation delivery) and active physician time (first to second CBCT) were recorded. PTV_4000 V95 %, PTV_2500 V9 5%, and D0.03 cc to stomach, duodenum and bowel were reported for scheduled (S) and adapted (A) plans. CTCAEv5.0 toxicities were recorded. Statistical analysis was performed using a two-sided T test and α of 0.05. Results: 21 patients with unresectable or locally-recurrent PDAC were analyzed, with a total of 105 fractions. Average total time was 29 min and 16 s (16:36-49:40) and average active physician time was 19:41 min (9:25-39:34). All fractions were treated with adapted plans. 97 % of adapted plans met PTV_4000 V95.0 % >95.0 % coverage goal and 100 % of adapted plans met OAR dose constraints. Median follow up was 6.6 months. Only 1 patient experienced acute grade 3+ toxicity directly attributable to radiation. Only 1 patient experienced late grade 3+ toxicity directly attributable to radiation. Conclusions: Daily CT-based OART was associated with significantly reduced dose OARs while achieving superior PTV coverage. Given the relatively quick total treatment time, radiation delivery was generally well tolerated and easily incorporated into the clinic workflow. Our initial clinical experience demonstrates OART allows for safe dose escalation in the treatment of PDAC.

Investigating iRHOM2-Associated Transcriptional Changes in Tylosis With Esophageal Cancer.

Background and Aims: Survival rates for esophageal squamous cell carcinoma (ESCC) are extremely low due to the late diagnosis of most cases. An understanding of the early molecular processes that lead to ESCC may facilitate opportunities for early diagnosis; however, these remain poorly defined. Tylosis with esophageal cancer (TOC) is a rare syndrome associated with a high lifetime risk of ESCC and germline mutations in RHBDF2, encoding iRhom2. Using TOC as a model of ESCC predisposition, this study aimed to identify early-stage transcriptional changes in ESCC development. Methods: Esophageal biopsies were obtained from control and TOC individuals, the latter undergoing surveillance endoscopy, and adjacent diagnostic biopsies were graded as having no dysplasia or malignancy. Bulk RNA-Seq was performed, and findings were compared with sporadic ESCC vs normal RNA-Seq datasets. Results: Multiple transcriptional changes were identified in TOC samples, relative to controls, and many were detected in ESCC. Accordingly, pathway analyses predicted an enrichment of cancer-associated processes linked to cellular proliferation and metastasis, and several transcription factors were predicted to be associated with TOC and ESCC, including negative enrichment of GRHL2. Subsequently, a filtering strategy revealed 22 genes that were significantly dysregulated in both TOC and ESCC. Moreover, Keratin 17, which was upregulated in TOC and ESCC, was also found to be overexpressed at the protein level in 'normal' TOC esophagus tissue. Conclusion: Transcriptional changes occur in TOC esophagus prior to the onset of dysplasia, many of which are associated with ESCC. These findings support the utility of TOC to help reveal the early molecular processes that lead to sporadic ESCC.

Clinical Outcomes of a Novel Hybrid Transtibial Technique for Femoral Tunnel Drilling in Anterior Cruciate Ligament Reconstruction: A Large Single-Center Case Series With a Minimum 2-Year Follow-up.

Background: A novel hybrid transtibial (HTT) approach to femoral tunnel drilling in anterior cruciate ligament reconstruction (ACLR) has been developed that circumvents the need for knee hyperflexion and orients the graft in the most anatomic position without sacrificing the tunnel length or aperture. Hypothesis: Patients who underwent ACLR utilizing the HTT technique would achieve excellent patient-reported outcome scores and experience low rates of graft failure and reoperations. Study Design: Case series; Level of evidence, 4. Methods: Patients who underwent primary ACLR at a single institution between 2005 and 2020 were retrospectively reviewed. Patients treated with the HTT, anteromedial portal (AMP), and transtibial (TT) approaches were matched based on age, sex, and body mass index ±3 kg/m2. Demographic and surgical data as well as femoral tunnel angle measurements on anteroposterior and lateral radiographs were collected for the 3 groups. However, clinical outcomes were only reported for the HTT group because of concerns of graft heterogeneity. Results: A total of 170 patients (median age, 26.5 years [interquartile range (IQR), 18.0-35.0 years]) who underwent ACLR using the HTT approach were included. The median coronal- and sagittal-plane femoral tunnel angles were 47° (IQR, 42°-53°) and 40° (IQR, 34°-46°), respectively. The sagittal-plane femoral tunnel angles in the HTT group were significantly more horizontal compared with those in the TT group (P < .0001), whereas the coronal-plane femoral tunnel angles in the HTT group were found to be significantly more vertical compared with those in the AMP group (P = .001) and more horizontal compared with those in the TT group (P < .0001). The graft failure and reoperation rates in the HTT group at a minimum 2-year follow-up were 1.8% (3/170) and 4.7% (8/170), respectively. The complication rate was 6.5% (11/170), with the most common complication being subjective stiffness in 7 patients. The median Lysholm score was 89.5 (IQR, 79.0-98.0); the median International Knee Documentation Committee score was 83.9 (IQR, 65.5-90.8); and the median Veterans RAND 12-Item Health Survey physical and mental component summary scores were 55.0 (IQR, 52.6-55.9) and 56.2 (IQR, 49.1-59.3), respectively. Conclusion: ACLR using the HTT technique was associated with low graft retear and revision surgery rates and good patient-reported outcome scores at medium-term follow-up and demonstrated femoral tunnel obliquity on postoperative radiographs that correlated with optimal parameters previously reported in cadaveric and biomechanical studies.

Varicella Zoster Virus disrupts MAIT cell polyfunctional effector responses.

Mucosal-associated invariant T (MAIT) cells are unconventional T cells that respond to riboflavin biosynthesis and cytokines through TCR-dependent and -independent pathways, respectively. MAIT cell activation plays an immunoprotective role against several pathogens, however the functional capacity of MAIT cells following direct infection or exposure to infectious agents remains poorly defined. We investigated the impact of Varicella Zoster Virus (VZV) on blood-derived MAIT cells and report virus-mediated impairment of activation, cytokine production, and altered transcription factor expression by VZV infected (antigen+) and VZV exposed (antigen-) MAIT cells in response to TCR-dependent and -independent stimulation. Furthermore, we reveal that suppression of VZV exposed (antigen-) MAIT cells is not mediated by a soluble factor from neighbouring VZV infected (antigen+) MAIT cells. Finally, we demonstrate that VZV impairs the cytolytic potential of MAIT cells in response to riboflavin synthesising bacteria. In summary, we report a virus-mediated immune-evasion strategy that disarms MAIT cell responses.

Review of the Patient Burden and Therapeutic Landscape of Irritable Bowel Syndrome with Constipation in the United States.

Irritable bowel syndrome (IBS) is a common disorder of the gut-brain axis. IBS with constipation (IBS-C) accounts for approximately one-third of IBS cases and is associated with substantial burden of illness and decreased quality of life. This narrative review provides an overview of the current and upcoming treatment options and disease management for IBS-C from a US perspective and discusses the importance of the relationship between patient and health care provider in diagnosis and treatment. A positive diagnostic strategy for IBS-C is recommended, based on clinical history, physical examination, and minimal laboratory tests. An effective communication strategy between patients and health care professionals is essential to ensure early diagnosis and reduce both health care costs and overall disease burden. Treatment typically begins with lifestyle interventions and nonpharmacologic options, such as dietary interventions, fiber supplements, and osmotic laxatives. In patients with inadequate response to these therapies, 4 currently available therapies (lubiprostone, linaclotide, plecanatide, and tenapanor) approved by the US Food and Drug Administration may relieve IBS-C symptoms. These agents are generally well tolerated and efficacious in improving IBS-C symptoms, including constipation and abdominal pain. In patients with persistent abdominal pain and/or psychological symptoms, brain-gut behavioral therapy or neuromodulator therapy may be beneficial.

Conserved sequence features in intracellular domains of viral spike proteins.

Viral spike proteins mutate frequently, but conserved features within these proteins often have functional importance and can inform development of anti-viral therapies which circumvent the effects of viral sequence mutations. Through analysis of large numbers of viral spike protein sequences from several viral families, we found highly (>99%) conserved patterns within their intracellular domains. The patterns generally consist of one or more basic amino acids (arginine or lysine) adjacent to a cysteine, many of which are known to undergo acylation. These patterns were not enriched in cellular proteins in general. Molecular dynamics simulations show direct electrostatic and hydrophobic interactions between these conserved residues in hemagglutinin (HA) from influenza A and B and the phosphoinositide PIP2. Super-resolution microscopy shows nanoscale colocalization of PIP2 and several of the same viral proteins. We propose the hypothesis that these conserved viral spike protein features can interact with phosphoinositides such as PIP2.

Ancestry-, Sex-, and Age-Based Differences of Gene Alterations in NSCLC: From the Real-World Data of Cancer Genomic Profiling Tests.

BACKGROUND: Some genomic alterations in non-small cell lung cancer (NSCLC) are known to differ according to race, sex, or age. These studies have been limited in sample size and thus they cannot detect the differences precisely and comprehensively. METHODS: Tissue-based comprehensive genomic profiling was performed on 75,362 patients with NSCLC from the United States during routine clinical care. Additionally, we examined data of a Japanese NSCLC cohort with 1,019 patients. In the US cohort, 296 genes were examined for pathogenic alterations. Predominant genetic ancestry was inferred using a SNP-based approach, and patients were categorized into European (EUR), African (AFR), East Asian (EAS), Admixed American (AMR), and South Asian (SAS) ancestry groups. Patients were additionally stratified by histologic type, age (<40/≥40 years, <75/≥75 years), and sex. The prevalence of high tumor mutational burden (TMB-High) and microsatellite instability status was also calculated. RESULTS: Stratified by ancestry, EGFR alterations were significantly enriched in EAS versus other ancestry groups. The prevalence of ALK was significantly higher in the AMR, EAS, and SAS patients than in AFR and EUR patients. KRAS and STK11 were enriched in EUR and AFR patients versus other groups. TMB-High was significantly enriched in AFR patients versus all other groups. An analysis based on sex revealed differences in prevalence of alterations in 80 genes and TMB-High status. For example, EGFR, ALK, BRAF, and KRAS alterations were significantly enriched in females, whereas TP53, STK11, KEAP1, and TMB-High were significantly enriched in males. With respect to age, the prevalence of alterations in 41 genes, including ALK, RET, MET, EGFR, STK11, KEAP1, BRAF, and KRAS, as well as TMB-High, were significantly different between patients aged <40 years and those aged ≥40 years. CONCLUSIONS: Comprehensive analysis from a large real-world dataset revealed ancestry-associated differences in genomic alterations in NSCLC. Age- and sex-related differences in prevalence of genomic alterations and TMB-High status were also observed.

A Qualitative Study of Aboriginal Peoples' Health Care Experiences With Chronic Obstructive Pulmonary Disease.

Aboriginal Australians experience a high prevalence of chronic obstructive pulmonary disease (COPD), with high rates of potentially preventable hospitalisations. However, little is known about Aboriginal peoples' experiences of living with COPD and how they navigate health care systems. This study used thematic analysis and Aboriginal methodology to explore Aboriginal peoples' lived experiences of COPD, their health care journey from receiving a diagnosis of COPD to the clinical management, and the impact of COPD on their daily lives. We conducted in-depth semi-structured interviews over a 6-month period with 18 Aboriginal adults diagnosed with COPD from four Aboriginal Community Controlled Health Services (ACCHS) in New South Wales, Australia. Reflexive thematic analysis was employed to ensure rigour. The findings revealed deeply personal and reflective stories shaped by historical, social, and cultural realities of Aboriginal peoples living with COPD. Four themes were identified characterising their experiences. Based on the findings, the following guidance is provided on future COPD care for Aboriginal peoples: Better alignment of existing COPD management with Aboriginal peoples' cultural contexts and perspectives to improve access to culturally safe care; Increased funding for ACCHS to enhance COPD management, such as early detection through case finding and access to ACCHS-led pulmonary rehabilitation; Engaging family members in COPD management and providing culturally centred COPD education that facilitates discussions and builds health literacy and self-management skills; Implementing health promotion initiatives to increase awareness and counteract fear and shame to improve early COPD detection.

Contextual determinants of family-driven care implementation in juvenile justice settings.

INTRODUCTION: Engaging families in behavioral health services is a high priority for juvenile justice (JJ) systems and family advocacy groups. Family-driven care (FDC) enhances family engagement and decision-making power in youth behavioral health services, ultimately, improving youth and family mental health and substance abuse outcomes. Despite the benefits, there is limited guidance on how to integrate FDC into behavioral health care within the JJ system. Therefore, the goal of this study is to understand factors that promoted adoption of FDC the JJ context. METHODS: JJ staff and leadership across the state of Georgia participated in surveys and interviews to understand contextual implementation determinants related to the adoption of FDC. Between November 2021- July 2022, 140 JJ staff participated in the survey from 61 unique JJ organizations. In addition, 16 staff participated in follow-up key informant interviews to explain quantitative findings. RESULTS: Based on a mixed methods analysis, JJ agencies were more likely to implement FDC if they had the following characteristics: (1) presence of site leaders that were strongly committed to family engagement, (2) a shared understanding that family engagement was a top priority, (3) staff training related to family engagement, (4) external partnerships with organizations that serve families, (5) a workplace culture that was supportive of innovation, and (6) presence of family engagement programs that were easier (or more feasible) for staff to implement. DISCUSSION: This mixed methods study underscores the importance of strengthening these 6 inner and outer setting implementation determinants when preparing to integrate FDC into JJ systems. Findings are used to promote the adoption and delivery of this high priority intervention in a state-level JJ system.

The effect of early childhood non-nutritive sucking behavior including pacifiers on malocclusion: a randomized controlled trial.

BACKGROUND/RATIONALE: Systematic reviews on the effects of pacifiers on occlusion have highlighted the need for quality RCTs. TRIAL DESIGN: Single region, three parallel-armed, prospective, randomized controlled trial. OBJECTIVES: To investigate the correlations between early childhood non-nutritive sucking habits and malocclusion. Specifically to test whether the use of a study pacifier has differing effects compared to other pacifiers and control, and whether the duration of pacifier use or digit sucking influence the occlusion. PARTICIPANTS: The subjects were firstborn children, born in 2008 in Vantaa, Finland. INTERVENTION: One-third of participants were offered study pacifiers, free of charge, from birth up to 2 years of age. The history of the subjects' sucking habits, including pacifier use was screened in a questionnaire at the age of 2 years, and clinical examinations were performed at the age of 7 years. In addition, the subjects were divided into groups that were equally matched regarding their mother's level of education. OUTCOMES: Posterior crossbite, anterior crossbite, overjet, deep bite, open bite, and crowding. RANDOMIZATION METHOD: Three districts were randomly allocated to three study groups by drawing lots. BLINDING: It was not possible to blind the clinicians or parents from the intervention. Blinding during data analysis was performed. RESULTS: From the original cohort of 2715 children born in the town of Vantaa, 1911 were excluded and 353 were lost to follow-up. The remaining 451 children were divided into three groups according to the use of pacifiers. The prevalence of posterior crossbite at the age of 7 years was higher if a non-study pacifier had been used (P = .005) even when matched for the mother's level of education (P = .029). The prevalence of posterior crossbite was higher if the pacifier habit had continued for 12 months or more compared to 11 months or less, 7% and 1%, respectively, (P = .003). Digit sucking for 12 months or more was associated with crowding (P = .016). The prevalence of crossbite in the study pacifier group was less than in control pacifiers. HARMS: No adverse harms were reported other than effects on the dentition. CONCLUSION: The use of pacifiers is associated with the posterior crossbite, especially if their use continues for a year or more. Parents/guardians should be advised to stop the use or reduce the use of pacifiers to a minimum after their child's first birthday. TRIAL REGISTRATION: ClinicalTrials.gov NCT01854502.