Two-point optical manipulation reveals mechanosensitive remodeling of cell-cell contacts in vivo.

Biological tissues acquire reproducible shapes during development through dynamic cell behaviors. Most of these behaviors involve the remodeling of cell-cell contacts. During epithelial morphogenesis, contractile actomyosin networks remodel cell-cell contacts by shrinking and extending junctions between lateral cell surfaces. However, actomyosin networks not only generate mechanical stresses but also respond to them, confounding our understanding of how mechanical stresses remodel cell-cell contacts. Here, we develop a two-point optical manipulation method to impose different stress patterns on cell-cell contacts in the early epithelium of the Drosophila embryo. The technique allows us to produce junction extension and shrinkage through different push and pull manipulations at the edges of junctions. We use these observations to expand classical vertex-based models of tissue mechanics, incorporating negative and positive mechanosensitive feedback depending on the type of remodeling. In particular, we show that Myosin-II activity responds to junction strain rate and facilitates full junction shrinkage. Altogether our work provides insight into how stress produces efficient deformation of cell-cell contacts in vivo and identifies unanticipated mechanosensitive features of their remodeling.

PbABCG1 and PbABCG2 transporters are required for the emission of floral monoterpenes in Phalaenopsis bellina.

Terrestrial plants emit volatiles into the atmosphere to attract both pollinators and the enemies of herbivores, for defense. Phalaenopsis bellina is a scented orchid species in which the main scent components are monoterpenes, including linalool and geraniol, and their derivatives. Here, we investigated whether ABC transporters are involved in floral scent emission. We carried out whole-genome identification of ABC transporter-related genes using four floral transcriptomics libraries of P. bellina. We identified 86 ABC subfamily G genes related to terpenoid transport. After comparing the gene expression patterns of P. bellina with that of Phalaenopsis aphrodite subsp. formosana, a scentless species, followed by gene-to-gene correlation analysis, PbABCG1 and PbABCG2 were selected. The temporal expression of both PbABCG1 and PbABCG2 was highly correlated with that of the key enzyme PbGDPS and the major transcription factor PbbHLH4 in monoterpene biosynthesis, with optimal expression on day 5 post-anthesis. Spatial gene expression analysis showed that PbABCG1 was highly expressed in sepals, whereas PbABCG2 was expressed in the lip. Subcellular localization with a GFP fusion protein revealed that both PbABCG1 and PbABCG2 are cytoplasmic membrane proteins. Co-downregulation of PbABCG1 and PbABCG2 using both double-strand RNA interference and tobacco rattle virus-based gene silencing led to a significant decrease in monoterpene emission, accompanied by an increase in the internal monoterpene pools. Furthermore, ectopic expression of PbABCG1 and PbABCG2 in an ABC16- mutant yeast strain rescued its tolerance to geraniol. Altogether, our results indicate that PbABCG1 and PbABCG2 play substantial roles in monoterpene transport/emission in P. bellina floral scent.

Potential causal links of long-term exposure to PM2.5 and its chemical components with the risk of nasopharyngeal carcinoma recurrence: A 10-year cohort study in South China.

There is a lack of evidence from cohort studies on the causal association of long-term exposure to ambient fine particulate matter (PM2.5) and its chemical components with the risk of nasopharyngeal carcinoma (NPC) recurrence. Based on a 10-year prospective cohort of 1184 newly diagnosed NPC patients, we comprehensively evaluated the potential causal links of ambient PM2.5 and its chemical components including black carbon (BC), organic matter (OM), sulfate (SO4 2-), nitrate (NO3 -), and ammonium (NH4 +) with the recurrence risk of NPC using a marginal structural Cox model adjusted with inverse probability weighting. We observed 291 NPC patients experiencing recurrence during the 10-year follow-up and estimated a 33% increased risk of NPC recurrence (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 1.02-1.74) following each interquartile range (IQR) increase in PM2.5 exposure. Each IQR increment in BC, NH4 +, OM, NO3 -, and SO4 2- was associated with HRs of 1.36 (95%CI: 1.13-1.65), 1.35 (95%CI: 1.07-1.70), 1.33 (95%CI: 1.11-1.59), 1.32 (95%CI: 1.06-1.64), 1.31 (95%CI: 1.08-1.57). The elderly, patients with no family history of cancer, no smoking history, no drinking history, and those with severe conditions may exhibit a greater likelihood of NPC recurrence following exposure to PM2.5 and its chemical components. Additionally, the effect estimates of the five components are greater among patients who were exposed to high concentration than in the full cohort of patients. Our study provides solid evidence for a potential relationship between long-term exposure to PM2.5 and its components and the risk of NPC recurrence.

Membrane Tilt Drives Phase Separation of Adhesion Receptors.

Cell adhesion receptors are transmembrane proteins that bind cells to their environment. These proteins typically cluster into disk-shaped or linear structures. Here, we show that such clustering patterns spontaneously emerge when the receptor senses the membrane deformation gradient, for example, by reaching a lower-energy conformation when the membrane is tilted relative to the underlying binding substrate. Increasing the strength of the membrane gradient-sensing mechanism first yields isolated disk-shaped clusters and then long linear structures. Our theory is coherent with experimental estimates of the parameters, suggesting that a tilt-induced clustering mechanism is relevant in the context of cell adhesion.

A Nickel Anchored Covalent Organic Framework as Unimolecular Metallaphotocatalyst for Visible Light Driver C-P Bond Coupling Reaction.

The urgent need to develop a sustainable and environmentally friendly method for synthesizing organophosphine compounds is underscored by their extensive applications in organic synthesis, coordination chemistry, medicinal chemistry, and photoelectric materials. Metalated covalent organic frameworks (MCOFs), which seamlessly integrate the inherent photo properties of COF with the catalytic capabilities of metal ions, offer an optimal material for efficient transformation of organics sustainably. In this study, we introduce a simple COF with nickel anchorages (Bpy-COF-NiCl2 ) as a unimolecular metallaphotocatalytic system for effective C-P bond formation. This heterogeneous photocatalyst exhibits superior catalytic performance, achieving yields of up to 95 %, and demonstrates broad substrate tolerance and functional group reactivity. Notably, the metallaphotocatalytic system has demonstrated the capability to process aryl bromides to produce the desired product, a feat not previously reported. Finally, the production and reusability test at the gram scale attests to its superior practicality for designing future organic cross-coupling reactions.

Impact of cash transfers on the association between prenatal exposures to high temperatures and low birthweight: Retrospective analysis from the LEAP 1000 study.

OBJECTIVE: To explore the associations between prenatal temperature exposures and low birthweight (LBW) and modification by cash transfer (CT) receipt. DESIGN: Retrospective cohort study. SETTING: Five rural districts in Northern Ghana. POPULATION OR SAMPLE: A total of 3016 infants born to women interviewed as part of the Livelihood Empowerment Against Poverty (LEAP 1000) impact evaluation between 2015 and 2017. METHODS: Birthweight was collected using household surveys administered to LEAP 1000 eligible women. We used a UNICEF-developed multiple imputation approach to address missingness of birthweight and applied an empirical heaping correction to the multiply imputed birthweight data. Survey data were linked to the European Centre for Medium-Range Weather Forecasts Reanalysis 5-hourly temperature averaged to weeks for 2011-2017 using community centroids. Using distributed-lag nonlinear models, we explored the lag-specific associations between weekly average temperatures greater than 30°C and LBW, and stratified by LEAP 1000 treatment. MAIN OUTCOME MEASURES: Low birthweight (<2.5 kg). RESULTS: Twelve percent (n = 365) of infants were LBW; the mean ± SD birthweight was 3.02 ± 0.37 kg. Overall, increasing temperatures were associated with increased odds of LBW, with the greatest odds observed in the 3 weeks before birth (odds ratio 1.005-1.025). These positive associations were even larger among comparison infants and null among treatment infants. CONCLUSIONS: Our study found increased odds of LBW with high weekly average temperatures throughout pregnancy and the preconception period and demonstrate mitigated effects by the LEAP 1000 CT program. More evidence on the potential of CTs to serve as adaptation interventions in low- and middle-income countries is needed to protect pregnant persons and their infants from the impacts of climate change.

Unveiling causal connections: Long-term particulate matter exposure and type 2 diabetes mellitus mortality in Southern China.

Evidence of the potential causal links between long-term exposure to particulate matters (PM, i.e., PM1, PM2.5, and PM1-2.5) and T2DM mortality based on large cohorts is limited. In contrast, the existing evidence usually suffers from inherent bias with the traditional association assessment. A prospective cohort of 580,757 participants in the southern region of China were recruited during 2009 and 2015 and followed up through December 2020. PM exposure at each residential address was estimated by linking to the well-established high-resolution simulation dataset. Hazard ratios (HRs) were calculated using time-varying marginal structural Cox models, an established causal inference approach, after adjusting for potential confounders. During follow-up, a total of 717 subjects died from T2DM. For every 1 µg/m3 increase in PM2.5, the adjusted HRs and 95% confidence interval (CI) for T2DM mortality was 1.036 (1.019-1.053). Similarly, for every 1 µg/m3 increase in PM1 and PM1-2.5, the adjusted HRs and 95% CIs were 1.032 (1.003-1.062) and 1.085 (1.054-1.116), respectively. Additionally, we observed a generally more pronounced impact among individuals with lower levels of education or lower residential greenness which as measured by the Normalized Difference Vegetation Index (NDVI). We identified substantial interactions between NDVI and PM1 (P-interaction = 0.003), NDVI and PM2.5 (P-interaction = 0.019), as well as education levels and PM1 (P-interaction = 0.049). The study emphasizes the need to consider environmental and socio-economic factors in strategies to reduce T2DM mortality. We found that PM1, PM2.5, and PM1-2.5 heighten the peril of T2DM mortality, with education and green space exposure roles in modifying it.

A feasibility study of a handmade ultrasound-guided phantom for paracentesis.

BACKGROUND: Simulation-based training is effective for ultrasound (US)-guided procedures. However, commercially developed simulators are costly. This study aims to evaluate the feasibility of a hand-made phantom for US-guided paracentesis. METHODS: We described the recipe to prepare an agar phantom. We collected the US performance data of 50 novices, including 22 postgraduate-year (PGY) residents and 28 undergraduate-year (UGY) students, who used the phantom for training, as well as 12 emergency residents with prior US-guided experience. We obtained the feedback after using the phantom with the Likert 5-point scale. The data were presented with medians and interquartile ranges (IQRs) and analyzed by the Wilcoxon rank sum test. RESULTS: While emergency residents demonstrated superior performance compared to trainees, all trainees exhibited acceptable proficiency (global rating of ≥ 3, 50/50 vs. 12/12, p = 1.000) and comparable needle steadiness [5 (5) vs. 5 (5), p = 0.223]. No significant difference in performance was observed between PGYs [5 (4-5)] and UGYs [5 (4-5), p = 0.825]. No significant differences were observed in terms of image stimulation, puncture texture, needle visualization, drainage simulation, and endurance of the phantom between emergency residents and trainees. However, experienced residents rated puncture texture and draining fluid as "neutral" (3/5 on the Likert scale). The cost of the paracentesis phantom is US$16.00 for at least 30 simulations, reducing it to US$6.00 without a container. CONCLUSIONS: The paracentesis phantom proves to be a practical and cost-effective training tool. It enables novices to acquire paracentesis skills, enhances their US proficiency, and boosts their confidence. Nevertheless, further investigation is needed to assess its long-term impact on clinical performance in real patients. TRIAL REGISTRATION: NCT04792203 at the ClinicalTrials.gov.

Clinical application and feasibility of capsule endoscopy in children at a medical center in central Taiwan.

BACKGROUND PURPOSE: Capsule endoscopy (CE) is a noninvasive examination for excellent visualization of small bowel mucosal lesions. We aimed to evaluate the clinical efficacy and safety of CE in pediatric patients. METHODS: From April 2014 to December 2022, CE procedures performed in children younger than 18 years of age at Taichung Veteran General Hospital were analyzed retrospectively. RESULTS: Among 136 procedures, the completion rate was 95.6% (n = 130), with a median age of 14 years old. Suspicion or evaluation of inflammatory bowel diseases (IBD) (41%) was the most common indication for CE. Other common indications of CE were chronic unexplained abdominal pain (35%) and obscure gastrointestinal bleeding or iron deficiency anemia (21%). No procedure-related complications occurred. The diagnosis of those patients with incomplete study were CD with small bowel stricture, graft-versus-host disease and duodenal ulcers. A total of 86 CE procedures showed positive findings, and the overall diagnostic yield rate was 63.2%. Small bowel ulcers (65.12%) were the most common findings. Overall, 26.5% of CE examinations resulted in a new diagnosis and 44.9% of CE exams led to a change in therapy. For patients with IBD, CE findings resulted in an even higher therapeutic change rate of 48.1%. CONCLUSIONS: CE is a safe and feasible diagnostic method to study the small intestine in children, especially for IBD. Incomplete study could be an indicator of positive finding and can potentially be a guide to identify the site of possible strictures.

Associations Between Ambient Extreme Heat Exposure and Emergency Department Visits Related to Kidney Disease.

RATIONALE & OBJECTIVE: Extreme heat exposure is associated with multiple diseases. However, our current understanding of the specific impact of extreme heat exposure on kidney disease is limited. STUDY DESIGN: Case-crossover study. SETTING & PARTICIPANTS: 1,114,322 emergency department (ED) visits with a principal diagnosis of kidney disease were identified in New York state, 2005-2013. EXPOSURE: Extreme heat exposure was defined as when the daily temperature exceeded the 90th percentile temperature of that month during the study period in the county. OUTCOME: ED visits with a principal diagnosis of kidney disease and its subtypes (ICD-9 [International Classification of Diseases, Ninth Revision] codes 580-599, 788). ANALYTICAL APPROACH: Extreme heat exposure on the ED visit days was compared with extreme heat exposure on control days using a conditional logistic regression model, controlling for humidity, air pollutants, and holidays. The excess risk of kidney disease was calculated for a week (lag days 0-6) after extreme heat exposure during the warm season (May through September). We also stratified our estimates by sociodemographic characteristics. RESULTS: Extreme heat exposure was associated with a 1.7% (lag day 0) to 3.1% (lag day 2) higher risk of ED visits related to kidney disease; this association was stronger with a greater number of extreme heat exposure days in the previous week. The association with extreme heat exposure lasted for an entire week and was stronger in the transitional months (ie, May and September; excess rates ranged from 1.8% to 5.1%) rather than the summer months (June through August; excess rates ranged from 1.5% to 2.7%). The strength of association was greater among those with ED visits related to acute kidney injury, kidney stones, and urinary tract infections. Age and sex may modify the association between extreme heat exposure and ED visits. LIMITATIONS: Individual exposure to heat-how long people were outside or whether they had access to air conditioning-was unknown. CONCLUSIONS: Extreme heat exposure was significantly associated with a dose-dependent greater risk of ED visits for kidney disease.

Structure and Rheology in Vertex Models under Cell-Shape-Dependent Active Stresses.

Biological cells can actively tune their intracellular architecture according to their overall shape. Here we explore the rheological implication of such coupling in a minimal model of a dense cellular material where each cell exerts an active mechanical stress along its axis of elongation. Increasing the active stress amplitude leads to several transitions. An initially hexagonal crystal motif is first destabilized into a solid with anisotropic cells whose shear modulus eventually vanishes at a first critical activity. Increasing activity beyond this first critical value, we find a re-entrant transition to a regime with finite hexatic order and finite shear modulus, in which cells arrange according to a rhombile pattern with periodically arranged rosette structures. The shear modulus vanishes again at a third threshold beyond which spontaneous tissue flows and topological defects of the nematic cell shape field arise. Flow and stress fields around the defects agree with active nematic theory, with either contractile or extensile signs, as also observed in several epithelial tissue experiments.

Clinical outcome is distinct between radiological stricture and endoscopic stricture in ileal Crohn's disease.

OBJECTIVES: Differences in clinical adverse outcomes (CAO) based on different intestinal stricturing definitions in Crohn's disease (CD) are poorly documented. This study aims to compare CAO between radiological strictures (RS) and endoscopic strictures (ES) in ileal CD and explore the significance of upstream dilatation in RS. METHODS: This retrospective double-center study included 199 patients (derivation cohort, n = 157; validation cohort, n = 42) with bowel strictures who simultaneously underwent endoscopic and radiologic examinations. RS was defined as a luminal narrowing with wall thickening relative to the normal gut on cross-sectional imaging (group 1 (G1)), which further divided into G1a (without upstream dilatation) and G1b (with upstream dilatation). ES was defined as an endoscopic non-passable stricture (group 2 (G2)). Strictures met the definitions of RS (with or without upstream dilatation) and ES were categorized as group 3 (G3). CAO referred to stricture-related surgery or penetrating disease. RESULTS: In the derivation cohort, G1b (93.3%) had the highest CAO occurrence rate, followed by G3 (32.6%), G1a (3.2%), and G2 (0%) (p < 0.0001); the same order was found in the validation cohort. The CAO-free survival time was significantly different among the four groups (p < 0.0001). Upstream dilatation (hazard ratio, 1.126) was a risk factor for predicting CAO in RS. Furthermore, when upstream dilatation was added to diagnose RS, 17.6% of high-risk strictures were neglected. CONCLUSIONS: CAO differs significantly between RS and ES, and clinicians should pay more attention to strictures in G1b and G3. Upstream dilatation has an important impact on the clinical outcome of RS but may not be an essential factor for RS diagnosis. CLINICAL RELEVANCE STATEMENT: This study explored the definition of intestinal stricture with the greatest significance for the clinical diagnosis and prognosis of patients with CD, and consequently provided effective auxiliary information for clinicians to formulate strategies for the treatment of CD intestinal strictures. KEY POINTS: • The retrospective double-center study showed that clinical adverse outcome is different between radiological strictures and endoscopic strictures in CD. • Upstream dilatation has an important impact on the clinical outcome of radiological strictures but may not be an essential factor for diagnosis of radiological strictures. • Radiological stricture with upstream dilatation and simultaneous radiological and endoscopic stricture were at increased risk for clinical adverse outcomes; thus, closer monitoring should be considered.

The role of input imaging combination and ADC threshold on segmentation of acute ischemic stroke lesion using U-Net.

BACKGROUND: To evaluate the effect of the weighting of input imaging combo and ADC threshold on the performance of the U-Net and to find an optimized input imaging combo and ADC threshold in segmenting acute ischemic stroke (AIS) lesion. METHODS: This study retrospectively enrolled a total of 212 patients having AIS. Four combos, including ADC-ADC-ADC (AAA), DWI-ADC-ADC (DAA), DWI-DWI-ADC (DDA), and DWI-DWI-DWI (DDD), were used as input images, respectively. Three ADC thresholds including 0.6, 0.8 and 1.8 × 10-3 mm2/s were applied. Dice similarity coefficient (DSC) was used to evaluate the segmentation performance of U-Nets. Nonparametric Kruskal-Wallis test with Tukey-Kramer post-hoc tests were used for comparison. A p < .05 was considered statistically significant. RESULTS: The DSC significantly varied among different combos of images and different ADC thresholds. Hybrid U-Nets outperformed uniform U-Nets at ADC thresholds of 0.6 × 10-3 mm2/s and 0.8 × 10-3 mm2/s (p < .001). The U-Net with imaging combo of DDD had segmentation performance similar to hybrid U-Nets at an ADC threshold of 1.8 × 10-3 mm2/s (p = .062 to 1). The U-Net using the imaging combo of DAA at the ADC threshold of 0.6 × 10-3 mm2/s achieved the highest DSC in the segmentation of AIS lesion. CONCLUSIONS: The segmentation performance of U-Net for AIS varies among the input imaging combos and ADC thresholds. The U-Net is optimized by choosing the imaging combo of DAA at an ADC threshold of 0.6 × 10-3 mm2/s in segmentating AIS lesion with highest DSC. KEY POINTS: • Segmentation performance of U-Net for AIS differs among input imaging combos. • Segmentation performance of U-Net for AIS differs among ADC thresholds. • U-Net is optimized using DAA with ADC = 0.6 × 10-3 mm2/s.

Environmental exposure disparities in ultrafine particles and PM2.5 by urbanicity and socio-demographics in New York state, 2013-2020.

BACKGROUND: The spatiotemporal and demographic disparities in exposure to ultrafine particles (UFP; number concentrations of particulate matter (PM) with diameter ≤0.1 µm), a key subcomponent of fine aerosols (PM2.5; mass concentrations of PM ≤ 2.5 µm), have not been well studied. OBJECTIVE: To quantify and compare the aerosol pollutant exposure disparities for UFP and PM2.5 by socio-demographic factors in New York State (NYS). METHODS: Ambient atmospheric UFP and PM2.5 were quantified using a global three-dimensional model of chemical transport with state-of-the-science aerosol microphysical processes validated extensively with observations. We matched these to U.S. census demographic data for varied spatial scales (state, county, county subdivision) and derived population-weighted aerosol exposure estimates. Aerosol exposure disparities for each demographic and socioeconomic (SES) indicator, with a focus on race-ethnicity and income, were quantified for the period 2013-2020. RESULTS: The average NYS resident was exposed to 4451 #·cm-3 UFP and 7.87 µg·m-3 PM2.5 in 2013-2020, but minority race-ethnicity groups were invariably exposed to greater daily aerosol pollution (UFP: +75.0% & PM2.5: +16.2%). UFP has increased since 2017 and is temporally and seasonally out-of-phase with PM2.5. Race-ethnicity exposure disparities for PM2.5 have declined over time; by -6% from 2013 to 2017 and plateaued thereafter despite its decreasing concentrations. In contrast, these disparities have increased (+12.5-13.5%) for UFP. The aerosol pollution exposure disparities were the highest for low-income minorities and were more amplified for UFP than PM2.5. DISCUSSION: We identified large disparities in aerosol pollution exposure by urbanization level and socio-demographics in NYS residents. Jurisdictions with higher proportions of race-ethnicity minorities, low-income residents, and greater urbanization were disproportionately exposed to higher concentrations of UFP and PM2.5 than other NYS residents. These race-ethnicity exposure disparities were much larger, more disproportionate, and unabating over time for UFP compared to PM2.5 across various income strata and levels of urbanicity.

Impact of heat on all-cause and cause-specific mortality: A multi-city study in Texas.

BACKGROUND: Studies on the health effects of heat are particularly limited in Texas, a U.S. state in the top 10 highest number of annual heat-related deaths per capita from 2018 to 2020. This study assessed the effects of heat on all-cause and cause-specific mortality in 12 metropolitan statistical areas (MSAs) across Texas from 1990 to 2011. METHODS: First, we determined the heat thresholds for each MSA above which the relation between temperature and mortality is linear. We then conducted a distributed lag non-linear model for each MSA, followed by a random effects meta-analysis to estimate the pooled effects for all MSAs. We repeated this process for each mortality cause and age group to achieve the effect estimates. RESULTS: We found a 1 °C temperature increase above the heat threshold is associated with an increase in the relative risk of all-cause mortality of 0.60% (95%CI [0.39%, 0.82%]) and 1.10% (95%CI [0.65%, 1.56%]) for adults older than 75. For each MSA, the relative risk of mortality for a 1 °C temperature increase above the heat threshold ranges from 0.10% (95%CI [0.09%, 0.10%]) to 1.29% (95%CI [1.26%, 1.32%]). Moreover, elevated temperatures showed a slight decrease in cardiovascular mortality (0.37%, 95%CI [-0.35%, 1.09%]) and respiratory disease (1.97%, 95%CI [-0.11%, 4.08%]), however this effect was not considered statistically significant.. CONCLUSION: Our study found that high temperatures can significantly impact all-cause mortality in Texas, and effect estimates differ by MSA, age group, and cause of death. Our findings generate critical information on the impact of heat on mortality in Texas, providing insights for policymakers on resource allocation and strategic intervention to reduce heat-related health effects.

Triggering of ST-elevation myocardial infarction by ultrafine particles in New York: Changes following Tier 3 vehicle introduction.

BACKGROUND: Previously, we found increased rates of ST-elevation myocardial infarction (STEMI) associated with increased ultrafine particle (UFP; <100 nm) concentrations in the previous few hours in Rochester, New York. Relative rates were higher after air quality policies and a recession reduced pollutant concentrations (2014-2016 versus 2005-2013), suggesting PM composition had changed and the same PM mass concentration had become more toxic. Tier 3 light duty vehicles, which should produce less primary organic aerosols and oxidizable gaseous compounds, likely making PM less toxic, were introduced in 2017. Thus, we hypothesized we would observe a lower relative STEMI rate in 2017-2019 than 2014-2016. METHODS: Using STEMI events treated at the University of Rochester Medical Center (2014-2019), UFP and other pollutants measured in Rochester, a case-crossover design, and conditional logistic regression models, we estimated the rate of STEMI associated with increased UFP and other pollutants in the previous hours and days in the 2014-2016 and 2017-2019 periods. RESULTS: An increased rate of STEMI was associated with each 3111 particles/cm3 increase in UFP concentration in the previous hour in 2014-2016 (lag hour 0: OR = 1.22; 95% CI = 1.06, 1.39), but not in 2017-2019 (OR = 0.94; 95% CI = 0.80, 1.10). There were similar patterns for black carbon, UFP11-50nm, and UFP51-100nm. In contrast, increased rates of STEMI were associated with each 0.6 ppb increase in SO2 concentration in the previous 120 h in both periods (2014-2016: OR = 1.26, 95% CI = 1.03, 1.55; 2017-2019: OR = 1.21, 95% CI = 0.87, 1.68). CONCLUSIONS: Greater rates of STEMI were associated with short term increases in concentrations of UFP and other motor vehicle related pollutants before Tier 3 introduction (2014-2016), but not afterwards (2017-2019). This change may be due to changes in PM composition after Tier 3 introduction, as well as to increased exposure misclassification and greater underestimation of effects from 2017 to 2019.

The dose-response association between LEAP 1000 and birthweight - no clear mechanisms: a structural equation modeling approach.

BACKGROUND: Birthweight is an important indicator of maternal and fetal health globally. The multifactorial origins of birthweight suggest holistic programs that target biological and social risk factors have great potential to improve birthweight. In this study, we examine the dose-response association of exposure to an unconditional cash transfer program before delivery with birthweight and explore the potential mediators of the association. METHODS: Data for this study come from the Livelihood Empowerment Against Poverty (LEAP) 1000 impact evaluation conducted between 2015 and 2017 among a panel sample of 2,331 pregnant and lactating women living in rural households of Northern Ghana. The LEAP 1000 program provided bi-monthly cash transfers and premium fee waivers to enroll in the National Health Insurance Scheme (NHIS). We used adjusted and unadjusted linear and logistic regression models to estimate the associations of months of LEAP 1000 exposure before delivery with birthweight and low birthweight, respectively. We used covariate-adjusted structural equation models (SEM) to examine mediation of the LEAP 1000 dose-response association with birthweight by household food insecurity and maternal-level (agency, NHIS enrollment, and antenatal care) factors. RESULTS: Our study included a sample of 1,439 infants with complete information on birthweight and date of birth. Nine percent of infants (N = 129) were exposed to LEAP 1000 before delivery. A 1-month increase in exposure to LEAP 1000 before delivery was associated with a 9-gram increase in birthweight and 7% reduced odds of low birthweight, on average, in adjusted models. We found no mediation effect by household food insecurity, NHIS enrollment, women's agency, or antenatal care visits. CONCLUSIONS: LEAP 1000 cash transfer exposure before delivery was positively associated with birthweight, though we did not find any mediation by household- or maternal-level factors. The results of our mediation analyses may serve to inform program operations and improve targeting and programming to optimize health and well-being among this population. TRIAL REGISTRATION: The evaluation is registered in the International Initiative for Impact Evaluation's (3ie) Registry for International Development Impact Evaluations (RIDIESTUDY- ID-55942496d53af) and in the Pan African Clinical Trial Registry (PACTR202110669615387).

Retracted: Long Noncoding RNA TP73-AS1 Targets MicroRNA-329-3p to Regulate Expression of the SMAD2 Gene in Human Cervical Cancer Tissue and Cell Lines.

The Editors of Medical Science Monitor wish to inform you that the above manuscript has been retracted from publication due to concerns with the credibility and originality of the study, the manuscript content, and the Figure images. Reference: Mei Mei Guan, Qun Xian Rao, Miao Ling Huang, Li Juan Wang, Shao Dan Lin, Qing Chen, Chang Hao Liu. Long Noncoding RNA TP73-AS1 Targets MicroRNA-329-3p to Regulate Expression of the SMAD2 Gene in Human Cervical Cancer Tissue and Cell Lines. Med Sci Monit, 2019; 25: 8131-8141. DOI: 10.12659/MSM.916292.

Post-traumatic distal ulnar bifurcation in children: a case report.

BACKGROUND: Galeazzi fracture dislocation is a compound injury that encompasses fractures of the distal third of the radius and dislocation of the distal radial ulnar joint (DRUJ). Clinically, this condition is rare and often leads to distal ulnar bifurcation. In previous similar reports, patients were effectively managed through surgery. CASE PRESENTATION: In this case report, we describe an 11-year-old male child who presented with an ulnar bifida following trauma to the hand, and was treated with manipulation and conservative treatment without surgery. A follow-up performed over the years demonstrated that the patient recovered well, and had normal wrist movements without significant pain, and the patient expressed great satisfaction. CONCLUSIONS: Ulnar diaphyseal fracture may occur in children or adolescents due to injuries, and may be accompanied with manipulation and repositioning. Conservative treatment can be applied to avoid the trauma associated with surgery especially in the absence of severe joint mobility impairment with good outcomes.

TLR7 Mediates Acute Respiratory Distress Syndrome in Sepsis by Sensing Extracellular miR-146a.

TLR7 (Toll-like receptor 7), the sensor for single-stranded RNA, contributes to systemic inflammation and mortality in murine polymicrobial sepsis. Recent studies show that extracellular miR-146a-5p serves as a TLR7 ligand and plays an important role in regulating host innate immunity. However, the role of miR-146a-5p and TLR7 signaling in pulmonary inflammation, endothelial activation, and sepsis-associated acute respiratory distress syndrome remains unclear. Here, we show that intratracheal administration of exogenous miR-146a-5p in mice evokes lung inflammation, activates endothelium, and increases endothelial permeability via TLR7-dependent mechanisms. TLR7 deficiency attenuates pulmonary barrier dysfunction and reduces lung inflammatory response in a murine sepsis model. Moreover, the impact of miR-146a-5p-TLR7 signaling on endothelial activation appears to be a secondary effect because TLR7 is undetectable in the human pulmonary artery and microvascular endothelial cells (ECs), which show no response to direct miR-146a-5p treatment in vitro. Both conditioned media of miR-146a-5p-treated macrophages (Mϕ) and septic sera of wild-type mice induce a marked EC barrier disruption in vitro, whereas Mϕ conditioned media or septic sera of TLR7-/- mice do not exhibit such effect. Cytokine array and pathway enrichment analysis of the Mϕ conditioned media and septic sera identify TNFα (tumor necrosis factor α) as the main downstream effector of miR-146a-5p-TLR7 signaling responsible for the EC barrier dysfunction, which is further supported by neutralizing anti-TNFα antibody intervention. Together, these data demonstrate that TLR7 activation elicits pulmonary inflammation and endothelial barrier disruption by sensing extracellular miR-146a-5p and contributes to sepsis-associated acute respiratory distress syndrome.