Most nearby young star clusters formed in three massive complexes.

Efforts to unveil the structure of the local interstellar medium and its recent star-formation history have spanned the past 70 years (refs. 1-6). Recent studies using precise data from space astrometry missions have revealed nearby, newly formed star clusters with connected origins7-12. Nonetheless, mapping young clusters across the entire sky back to their natal regions has been hindered by a lack of clusters with precise radial-velocity data. Here we show that 155 out of 272 (57%) high-quality young clusters13,14 within 1 kiloparsec of the Sun arise from three distinct spatial volumes. This conclusion is based on the analysis of data from the third Gaia release15 and other large-scale spectroscopic surveys. At present, dispersed throughout the solar neighbourhood, their past positions more than 30 million years ago reveal that these families of clusters each formed in one of three compact, massive star-forming complexes. One of these families includes all of the young clusters near the Sun-the Taurus and Scorpius-Centaurus star-forming complexes16,17. We estimate that more than 200 supernovae were produced from these families and argue that these clustered supernovae produced both the Local Bubble18 and the largest nearby supershell GSH 238+00+09 (ref. 19), both of which are clearly visible in modern three-dimensional dust maps20-22.

The Regulate your Sitting Time (RESIT) intervention for reducing sitting time in individuals with type 2 diabetes: findings from a randomised-controlled feasibility trial.

BACKGROUND: Reducing and breaking up sitting is recommended for optimal management of Type 2 diabetes mellitus (T2DM). Yet, there is limited evidence of interventions targeting these outcomes in individuals with this condition. The primary aim of this study was to assess the feasibility and acceptability of delivering and evaluating a tailored online intervention to reduce and break up sitting in adults with T2DM. METHODS: A mixed-methods two-arm randomised controlled feasibility trial was conducted in ambulatory adults with T2DM who were randomised 1:1 to the REgulate your SItting Time (RESIT) intervention or usual care control group. The intervention included online education, self-monitoring and prompt tools (wearable devices, smartphone apps, computer apps) and health coaching. Feasibility outcomes were recruitment, attrition, data completion rates and intervention acceptability. Measurements of device-assessed sitting (intended primary outcome for definitive trial), standing and stepping, and physical function, psychosocial health and wellbeing were taken at baseline, 3 months and 6 months. Individual semi-structured interviews were conducted at six-months (post intervention) to explore acceptability, feasibility and experiences of the trial and intervention using the Framework Method. RESULTS: Seventy participants aged 55 ± 11 years were recruited. Recruitment rate (proportion of eligible participants enrolled into the study) was 67% and participant retention rate at 6 months was 93% (n = 5 withdrawals). Data completion rates for daily sitting were 100% at baseline and ranged from 83 to 91% at 3 months and 6 months. Descriptive analysis demonstrated potential for the intervention to reduce device-measured sitting, which was 30.9 ± 87.2 and 22.2 ± 82.5 min/day lower in the intervention group at 3 and 6 months, respectively, compared with baseline. In the control group, sitting was 4.4 ± 99.5 and 23.7 ± 85.2 min/day lower at 3 and 6 months, respectively. Qualitative analysis identified three themes: reasons for participating in the trial, acceptability of study procedures, and the delivery and experience of taking part in the RESIT intervention. Overall, the measurement visits and intervention were acceptable to participants. CONCLUSIONS: This study demonstrated the feasibility and acceptability of the RESIT intervention and evaluation methods, supporting a future definitive trial. If RESIT is found to be clinically effective, this could lead to changes in diabetes healthcare with a focus on reducing sitting. TRIAL REGISTRATION: The trial was registered with ISRCTN (number ISRCTN14832389).

Parent implementation of a treatment for late talkers based on cross-situational statistical learning principles: Treatment fidelity and acceptability.

PURPOSE: Early intervention based on principles of cross-situational statistical learning (CSSL) for late-talking children has shown promise. This study explored whether parents could be trained to deliver this intervention protocol with fidelity and if they found the intervention to be acceptable. METHOD: Mothers of four English-speaking children aged 18-30 months who scored <10th centile for expressive vocabulary were recruited to an 8-week group training program. Parents were taught principles of CSSL and asked to perform 16 home treatment sessions (30 minutes each) in total, providing auditory bombardment of target words in full sentences at high dose number and syntactic variability, using a range of physical exemplars. Home diaries and two videotaped sessions measured treatment fidelity. Pre- and post-treatment questionnaires measured acceptability. RESULT: One parent discontinued the study after the second group training session. Three parents completed 15/16 group training sessions and reported completing 87% of home sessions. Two parents demonstrated implementing the intervention as per the target dose number by the first fidelity session (Weeks 2/3), and the third parent was very close to meeting target dose number by the second fidelity session (Weeks 7/8). CONCLUSION: Parents can be trained to deliver an intervention based on cross-situational statistical learning principles.

Assessment of Developmental Language Disorder in Multilingual Children: Results from an International Survey.

INTRODUCTION: The Multilingual-Multicultural Affairs Committee of the International Association of Communication Disorders (IALP) conducted a survey of diagnostic criteria for developmental language disorder (DLD) in multilingual children to discover how clinicians apply terminology and diagnostic criteria to multilingual children in different parts of the world. METHODS: An international web survey was used to survey 354 participants from 44 countries about their assessment practices, and clinical opinions about assessing multilingual children for DLD. RESULTS: The findings show that most clinicians felt confident in assessing multilingual children, and they applied the DLD terminology and inclusionary criteria to multilingual children with difficulty learning language. Clinicians used different procedures to assess heritage and societal languages. Barriers to access to services included a lack of knowledge by parents and referral sources about services available and typical multilingual development, with additional reasons differing by geographical region. DISCUSSION: Speech pathologists across the globe have many similarities in the way that they assess multilingual children. Differences may be attributed to clinical experience, professional education, the clinician's role, the system they work in, and the clinician's own language skills. This paper advances knowledge of current clinical practices, which can be used to evaluate frameworks in international and national contexts, with implications for policy and practice to improve access to clinical services.

Replication of a single-case design cross-situational statistically based word learning treatment for late talking children.

PURPOSE: Late talking children are at risk of ongoing language impairment. This intervention study replicated and extended research based on cross-situational statistical learning principles. METHOD: Three late talking children (age 24-32 months) were enrolled into the concurrent multiple baseline single-case experimental intervention study. The intervention consisted of 16 sessions over eight/nine weeks, including 10-11 pairs of target and control words (three per session). Children heard the target words a minimum of 64 times per session, in sentences with high linguistic variability in varied play activities. RESULT: All children increased production of target words and expressive vocabulary, with statistically significant differences between word acquisition in baseline and intervention phases. One of the three children learnt statistically significantly more target words than control words. CONCLUSION: The results replicated the findings of previous research for some but not all of the participants, providing individual evidence that this approach has promise as a therapy technique for late talking children.

Enhancing asthma research and improving health equity through decentralized clinical trials (DCTs) and mHealth technology.

The COVID-19 pandemic led to widespread disruption and termination of clinical research and a prompt adoption of mobile health (mHealth) technologies in the healthcare space. As the United States' healthcare system has rapidly become reliant on remotely conducted activities, the implementation of decentralized methods using mHealth technology in research investigation has become a necessary alternative to traditional in-person cohort studies. The aim of this article is to: report successful and unsuccessful examples of remote asthma clinical studies, explore the benefits and potential drawbacks of virtual clinical investigation, discuss the potential impact on equity and representation in asthma research, and provide suggestions through which investigators can implement decentralized clinical trials. Enhanced study accessibility, participant diversity, safety measures, and research efficacy are some of the benefits identified with a focused discussion on the impact on equity that decentralized clinical trials renders. Furthermore, potential concerns regarding regulatory compliance, data privacy, and effective mHealth design and solutions are discussed. Despite the setbacks and interruptions faced by the study participants and investigators due to the pandemic, the transition to decentralized clinical studies using mHealth technology is a positive, feasible step toward innovation and equity in the allergy and immunology field.

Differential impact of the school context on ethnic and racial identity and depression for monoracial and multiracial early adolescents.

Introduction: This study examined the direct and indirect effects of school context (negative peer relationships, school environment) on ethnic and racial identity (ERI) development in middle school and later depression symptoms in high school. Differences by racial group were examined for non-Hispanic White (NHW) early adolescents, monoracial adolescents, and multiracial adolescents. Methods: This study used existing data from a large, multiwave, longitudinal study that included 593 racial/ethnically diverse adolescents from sixth grade through ninth grade across three public middle schools in the Pacific Northwest. Results: Using multigroup path analysis in structural equation modeling, the findings indicated differences by racial group-school environment was associated with positive ERI development in middle school for NHW and monoracial adolescents but not for multiracial adolescents. For multiracial adolescents, ERI predicted later depression symptoms. Discussion: These findings demonstrated the importance of examining school context and peer relationships in relation to ERI development and psychological wellbeing.

Fabrication of a Dual-Targeted Liposome-Coated Mesoporous Silica Core-Shell Nanoassembly for Targeted Cancer Therapy.

Nanoparticles have been suggested as drug-delivery systems for chemotherapeutic drugs to allow for controlled drug release profiles and selectivity to target cancer cells. In addition, nanoparticles can be used for the in situ generation and amplification of reactive oxygen species (ROS), which have been shown to be a promising strategy for cancer treatment. Thus, a targeted nanoscale drug-delivery platform could be used to synergistically improve cancer treatment by the action of chemotherapeutic drugs and ROS generation. Herein, we propose a promising chemotherapy strategy where the drug-loaded nanoparticles generate high doses of ROS together with the loaded ROS-generating chemotherapeutic drugs, which can damage the mitochondria and activate cell death, potentiating the therapeutic outcome in cancer therapy. In the present study, we have developed a dual-targeted drug-delivery nanoassembly consisting of a mesoporous silica core loaded with the chemotherapeutic, ROS-generating drug, paclitaxel (Px), and coated with a liposome layer for controlled drug release. Two different lung cancer-targeting ligands, folic acid and peptide GE11, were used to target the overexpressed nonsmall lung cancer receptors to create the final nanoassembly (MSN@Px) L-GF. Upon endocytosis by the cancer cells, the liposome layer was degraded by the intracellular lipases, and the drug was rapidly released at a rate of 65% within the first 20 h. In vitro studies confirmed that this nanoassembly was 8-fold more effective in cancer therapy compared to the free drug Px.

Bone Cement Fumes Generated in Laminar Airflow Versus Conventionally Ventilated Operating Rooms: Does the Mixing System Matter?

BACKGROUND: Bone cement is commonly utilized in a variety of orthopaedic procedures and contains methylmethacrylate (MMA) monomer. MMA is a colorless, clear, flammable liquid of intense odor. Its vapor concentration in the immediate breathing zone can vary considerably in the operative setting and, in higher concentrations, can become an occupational health hazard. Therefore, reducing MMA vapor is desirable. The aim of this study was to compare the MMA vapor levels emitted during mixing among 5 commercially available cement-mixing systems across 2 operative settings: an operating room (OR) with conventional ventilation (CV) and an OR with laminar airflow (LAF). METHODS: A prospective, in vitro study was conducted at a single hospital in an OR with LAF and in an OR with CV. MMA vapor release during the cement preparation of a SAWBONES femoral canal was measured with use of a calibrated MiniRAE 3000. A total of 5 different vacuum cement-mixing systems were utilized to mix the same cement type according to the manufacturer instructions of each system. MMA vapor concentrations were measured during 5 phases of mixing, and each mixing system was randomly utilized 10 times in each OR. RESULTS: When comparing the MMA concentration levels of each system between the 2 settings, emissions remained generally higher in the CV setting for every system and in nearly every phase. Among the 5 systems analyzed, System #5, the only entirely closed system, had the lowest overall emissions for each of the 5 phases in the CV setting. CONCLUSIONS: This study demonstrated that an operative environment with LAF is conducive to clearing the fumes of MMA during mixing as well as limiting the amount of time that residual fumes linger after mixing. Additionally, the entirely closed cement-mixing system was the most effective in minimizing fume levels within the CV setting. Utilizing this closed system, especially in an OR with CV, may reduce exposure to MMA fumes from bone cement, potentially creating a more favorable working environment. CLINICAL RELEVANCE: This study provides evidence that a closed cement-mixing system utilized under vacuum in both an OR with CV and an OR with LAF is effective in keeping MMA fume levels below those considered harmful by the U.S. Occupational Safety and Health Administration.

Dual Targeted Delivery of Liposomal Hybrid Gold Nano-Assembly for Enhanced Photothermal Therapy against Lung Carcinomas.

The delivery and accumulation of therapeutic drugs into cancer cells without affecting healthy cells are a major challenge for antitumor therapy. Here, we report the synthesis of a liposomal hybrid gold nano-assembly with enhanced photothermal activity for lung cancer treatment. The core components of the nano-assembly include gold nanorods coated with a mesoporous silica shell that offers an excellent drug-loading surface for encapsulation of doxorubicin. To enhance the photothermal capacity of nano-assembly, IR 780 dye was loaded inside a thermo-sensitive liposome, and then, the core nano-assembly was wrapped within the liposome, and GE-11 peptide and folic acid were conjugated onto the surface of the liposome to give the final nano-assembly [(GM@Dox) LI]-PF. The dual targeting approach of [(GM@Dox) LI]-PF leads to enhanced cellular uptake and improves the accumulation of nano-assemblies in cancer cells that overexpress the epidermal growth factor receptor and folate. The exposure of near-infrared laser irradiation can trigger photothermal-induced structural disruption of the nano-assembly, which allows for the precise and controllable release of Dox at targeted sites. Additionally, chemo-photothermal therapy was shown to be 11 times more effective in cancer cell treatment when compared to Dox alone. Our systematic study suggests that the nano-assemblies facilitate the cancer cells undergoing apoptosis via an intrinsic mitochondrial pathway that can be directly triggered by the chemo-photothermal treatment. This study offers an appealing candidate that holds great promise for synergistic cancer treatment.

Human synovial fluid interleukin-6, but not type II collagen breakdown, positively correlated with pain after anterior cruciate ligament injury and reconstruction.

Anterior cruciate ligament (ACL) injury initiates a biochemical cascade thought to contribute to the onset and progression of posttraumatic osteoarthritis (PTOA). Interleukin-1ß (IL-1ß), IL-6, and C-telopeptide fragments of type II collagen (CTX-II) are implicated in joint inflammation and cartilage degradation following ACL injury; however, their association with pain is still being explored. The purpose of this study was to evaluate the associations between synovial fluid concentrations of IL-1ß, IL-6, and CTX-II with pain following ACL injury and reconstruction. We hypothesized that greater IL-1ß, IL-6, and CTX-II would correlate with greater Pain Visual Analogue Scale (VAS) scores. This was a secondary analysis of 23 patients (mean age = 18.4 years, BMI = 27.4, 13 females/10 males) with acute ACL tears who participated in a pilot randomized trial. Synovial fluid and VAS scores were collected on the day of initial presentation, at ACL reconstruction, and 1 and 4 weeks after surgery. Synovial fluid concentrations of IL-1ß, IL-6, and CTX-II were assessed using enzyme-linked immunoabsorbent assays, and repeated measures correlations were used to assess the relationships between pain and synovial IL-1ß, IL-6, or CTX-II after ACL injury and reconstruction. Pain was positively correlated with synovial fluid IL-6 concentrations (r = 0.52, p < 0.001); however, pain was inversely correlated with CTX-II (r = -0.39, p = 0.002). IL-1ß had no significant correlation with pain. Statement of clinical relevance: PTOA has been described as a "silent killer" and these results suggest that early PTOA may have pro-inflammatory pathways that are not primarily associated with pain but still lead to progressive cartilage loss.

Pain Early After Anterior Cruciate Ligament Reconstruction is Associated With 6-Month Loading Mechanics During Running.

BACKGROUND: Anterior cruciate ligament reconstruction (ACLR) results in persistent altered knee biomechanics, but contributing factors such as pain or patient function, leading to the altered loading, are unknown. HYPOTHESIS: Individuals with worse self-reported pain after ACLR would have poorer biomechanics during running, and poor loading mechanics would be present in the ACLR limb compared with contralateral and control limbs. STUDY DESIGN: Cohort pilot study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 20 patients after ACLR (age, 18.4 ± 2.7 years; height, 1.7 ± 0.1 m; mass, 84.2 ± 19.4 kg) completed visual analog scale and Knee Injury and Osteoarthritis Outcomes Score (KOOS) at 1 and 6 months postsurgery. At 6 months postsurgery, patients underwent biomechanical testing during running. A total of 20 control individuals also completed running biomechanical analyses. Associations between patient outcomes and biomechanics were conducted, and differences in running biomechanics between groups were analyzed. RESULTS: KOOS pain score 1 month after surgery was associated with peak ACLR knee abduction moment (R2 = 0.35;P = 0.01). At 6-months, KOOS sport score was related to peak abduction moment in the ACLR limb (R2 = 0.23; P = 0.05). For change scores, the improvement in pain scores related to ACLR limb peak knee abduction moment (R2 = 0.55; P = 0.001). The ACLR limb had lower knee excursion, extension moments, and ground-reaction forces compared with the uninvolved and control limb. The uninvolved limb also had higher ground-reaction forces compared with the ACLR limb and control limb. CONCLUSION: These results suggest that patient-reported outcomes 1 and 6 months after surgery are associated with running mechanics 6 months after ACLR. Further, the underloading present in the ACLR limb and overloading in the uninvolved limb indicates greater need for running rehabilitation after ACLR. CLINICAL RELEVANCE: Understanding pain and how it may be linked to movement dysfunction is important for improving long-term outcomes.

Young adult male LEW.1WR1 rats have reduced beta cell area and develop glucose intolerance.

Prediabetes affects 1 in 3 American adults and is characterized by insulin resistance, insulin hypersecretion, and impaired glucose tolerance. Weanling LEW.1WR1 (1WR1) rats have increased blood insulin concentrations, so we hypothesized that young adult 1WR1 rats would develop impaired glucose tolerance due to the poor regulation of insulin. We monitored glucose tolerance, insulin tolerance, and weight gain for 10 weeks to assess if there was a decline in glucose processing over time. 1WR1 rats were significantly more glucose intolerant after 8 weeks. 1WR1 rats had increased body mass, yet abdominal fat mass was not significantly increased. Although the 1WR1 rats had increased circulating insulin and glucagon protein levels, 1WR1 rat beta cell area was significantly reduced. There may be underlying insulin resistance as evidenced by dysfunctional insulin regulation during fasting. Understanding the metabolic phenotype of this rat model can provide insight into the human pathophysiological changes that increase susceptibility to glucose intolerance and prediabetes.

Periostin regulation and cartilage degradation early after anterior cruciate ligament reconstruction.

OBJECTIVE AND DESIGN: The purpose of this study was to explore pathological processes during the first 4 weeks after anterior cruciate ligament reconstruction (ACLR). SUBJECTS: Sixteen ACL-injured patients (8 females/8 males, mean age = 19.1, mean BMI = 28.6). METHODS: Arthrocentesis was performed 1 and 4 weeks after ACLR. Proteins in the synovial fluid were identified using nanoLC-ESI-MS/MS. Differentially up- or down-regulated proteins were identified and quantified, and a pathway analysis was performed. All identified proteins were mapped into a protein-protein interaction (PPI) network, and networks of PPIs with a combined score > 0.9 were then visualized. RESULTS: Seven pathways were upregulated after ACLR: PI3K-AKT signaling pathway, extracellular matrix (ECM)-receptor interaction, focal adhesion, protein digestion and absorption, ameobiasis, and platelet activation. Network analyses identified 8 proteins that were differentially upregulated with strong PPI interactions (periostin and 7 collagen-related proteins). Increases in periostin moderately correlated with increases in a synovial fluid biomarker of type II cartilage degradation (ρ = 0.51, p = 0.06). CONCLUSION: Pro-inflammatory pathways and periostin were upregulated after ACLR. Periostin demonstrated strong network connections with markers of collagen breakdown, and future work is needed to determine whether periostin may offer a biomarker of early cartilage degradation after ACLR and/or play an active role in early post-traumatic osteoarthritis (PTOA) progression.

Complement system dysregulation in synovial fluid from patients with persistent inflammation following anterior cruciate ligament reconstruction surgery.

Introduction: Patients with anterior cruciate ligament injury are at high risk of posttraumatic osteoarthritis and their response to reconstructive surgery and rehabilitation vary. Proteins identified in the orchestration of the acute inflammatory response may be predictive of patient outcomes. Objective: An unbiased, bottom-up proteomics approach was used to discover novel targets for therapeutics in relation to dysregulation in the orchestration of inflammatory pathways implicated in persistent joint inflammation subsequent to joint trauma. Methods: Synovial fluid was aspirated from patients at 1 week and 4 weeks after anterior cruciate ligament reconstruction (ACLR) and interleukin 6 (IL-6) concentrations were quantified by enzyme-linked immunosorbent assay. Patients were segregated into IL-6low and IL-6high groups based on IL-6 concentrations in synovial fluid at 4-weeks postoperation and proteins in synovial fluid were analyzed using qualitative, bottom-up proteomics. Abundance ratios were calculated for IL-6high and IL-6low groups as 4 weeks postoperation:1 week postoperation. Results: A total of 291 proteins were detected in synovial fluid, 34 of which were significantly (P < .05) differentially regulated between groups. Proteins associated with the classical and alternative complement cascade pathways were increased in the IL-6high compared to IL-6low group. Insulin-like growth factor-binding protein 6 (IGFBP-6) was increased by nearly 60-fold in the IL-6low group. Conclusions: Patients segregated by IL-6 concentration in synovial fluid at 4 weeks post-ACLR demonstrated differential regulation of multiple pathways, providing opportunities to investigate novel targets, such as IGFBP-6, and to take advantage of therapeutics already approved for clinical use in other diseases that target inflammatory pathways, including the complement system.

The case for FAT10 as a novel target in fatty liver diseases.

Human leukocyte antigen F locus adjacent transcript 10 (FAT10) is a ubiquitin-like protein that targets proteins for degradation. TNFα and IFNγ upregulate FAT10, which increases susceptibility to inflammation-driven diseases like nonalcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), and hepatocellular carcinoma (HCC). It is well established that inflammation contributes to fatty liver disease, but how inflammation contributes to upregulation and what genes are involved is still poorly understood. New evidence shows that FAT10 plays a role in mitophagy, autophagy, insulin signaling, insulin resistance, and inflammation which may be directly associated with fatty liver disease development. This review will summarize the current literature regarding FAT10 role in developing liver diseases and potential therapeutic targets for nonalcoholic/alcoholic fatty liver disease and hepatocellular carcinoma.

Metabolite quantification: A fluorescence-based method for urine sample normalization prior to 1H-NMR analysis.

INTRODUCTION: Metabolomics is a multi-discipline approach to systems biology that provides a snapshot of the metabolic status of a cell, tissue, or organism. Metabolomics uses mass spectroscopy (MS) and nuclear magnetic resonance (NMR) to analyze biological samples for low molecular weight metabolites. OBJECTIVE: Normalize urine sample pre-acquisition to perform a targeted quantitative analysis of selected metabolites in rat urine. METHODS: Urine samples were provided from rats on a control diet (n = 10) and moderate sucrose diet (n = 8) collected in a metabolic cage during an eight hour fast. Urine from each sample was prepared by two different methods. One sample was a non-normalized sample of 1200 µL and the second sample was a variable volume-normalized to the concentration of urobilin in a standard sample of urine. The urobilin concentration in all samples was determined by fluorescence. Ten metabolites for each non-normalized and normalized urine sample were quantified by integration to an internal standard of DSS. RESULTS: Both groups showed an improvement in pH range going from non-normalized to normalized samples. In the group on the control diet, eight metabolites had significant improvement in range, while the remaining two metabolites had insignificant improvement in range comparing the non-normalized sample to the normalized sample. In the group on the moderate sucrose diet all ten metabolites showed significant improvement in range going from non-normalized to normalized samples. CONCLUSIONS: These findings describe a pre-acquisition method of urine normalization to adjust for differences in hydration state of each organism. This results in a narrower concentration range in a targeted analysis.

Can Dynamic Assessment Identify Language Disorder in Multilingual Children? Clinical Applications From a Systematic Review.

PURPOSE: Multilingual children are disproportionately represented on speech pathology caseloads, in part due to the limited ability of traditional language assessments to accurately capture multilingual children's language abilities. This systematic review evaluates the evidence for identification of language disorder in multilingual children using dynamic assessment and considers clinical applications of the evidence. METHOD: A systematic search of the Cumulative Index to Nursing and Allied Health Literature, Education Resources Information Centre, Education Source, Google Scholar, Linguistics, Medline, and PsycINFO databases produced 10 articles that met the inclusion criteria: between-groups comparison studies that used dynamic assessment to identify language disorder in children under 12 years old that spoke a different language at home to the majority society language. Articles were critically appraised using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) protocol. RESULTS: Nine of the 10 studies reported that their dynamic assessment identified language disorder in multilingual children. However, small sample sizes, limited language pairs, variability in the reference standard, and design deficiencies resulted in poor ratings for all studies on QUADAS-2. CONCLUSIONS: The studies in this review reflected an emergent area of research. Preliminary guidelines for clinical application indicate that dynamic assessment may be a suitable and time-efficient complementary method of diagnosis of language disorder in multilingual children. Further recommendations about age of use, language of instruction, and relevant scores are included.

Peripartal treatment with low-dose sertraline accelerates mammary gland involution and has minimal effects on maternal and offspring bone.

Women mobilize up to 10% of their bone mass during lactation to provide milk calcium. About 8%-13% of mothers use selective serotonin reuptake inhibitors (SSRI) to treat peripartum depression, but SSRIs independently decrease bone mass. Previously, peripartal use of the SSRI fluoxetine reduced maternal bone mass sustained post-weaning and reduced offspring bone length. To determine whether these effects were fluoxetine-specific or consistent across SSRI compounds, we examined maternal and offspring bone health using the most prescribed SSRI, sertraline. C57BL/6 mice were given 10 mg/kg/day sertraline, from the beginning of pregnancy through the end of lactation. Simultaneously, we treated nulliparous females on the same days as the primiparous groups, resulting in age-matched nulliparous groups. Dams were euthanized at lactation day 10 (peak lactation, n = 7 vehicle; n = 9 sertraline), lactation day 21 (weaning, n = 9 vehicle; n = 9 sertraline), or 3m post-weaning (n = 10 vehicle; n = 10 sertraline) for analysis. Offspring were euthanized at peak lactation or weaning for analysis. We determined that peripartum sertraline treatment decreased maternal circulating calcium concentrations across the treatment period, which was also seen in nulliparous treated females. Sertraline reduced the bone formation marker, procollagen 1 intact N-terminal propeptide, and tended to reduce maternal BV/TV at 3m post-weaning but did not impact maternal or offspring bone health otherwise. Similarly, sertraline did not reduce nulliparous female bone mass. However, sertraline reduced immunofluorescence staining of the tight junction protein, zona occludens in the mammary gland, and altered alveoli morphology, suggesting sertraline may accelerate mammary gland involution. These findings indicate that peripartum sertraline treatment may be a safer SSRI for maternal and offspring bone rather than fluoxetine.