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Determinants of Pain Perception and Patient Satisfaction in Dental Local Anesthesia: A Comprehensive Meta-Analysis of Verbal Cues, Mechanical Interventions, and the Expectancy Disconfirmation Model
Full text linkThe administration of local anesthesia represents a critical juncture in the provision of dental care, acting simultaneously as the primary facilitator of painless treatment and the most significant source of patient anxiety and avoidance behavior. This meta-analysis synthesizes data from an extensive review of peer-reviewed literature to deconstruct the multifactorial determinants of injection pain. We specifically isolate and evaluate the impact of verbal framing (euphemistic versus direct language), mechanical interventions (needle gauge, solution warming, vibration, computer-controlled delivery), and the overarching psychological framework of the Expectancy Disconfirmation Model (EDM). Our comprehensive synthesis indicates that while mechanical variables such as solution temperature and tactile vibration significantly modulate nociceptive input via physiological mechanisms like TRPV1 channel permeabilization and the Gate Control Theory, the patient's cognitive appraisal—shaped predominantly by verbal cues and pre-existing expectations—plays a dominant role in the final satisfaction outcome. We report that the framing of an injection using negative descriptors such as "hurt," "pinch," or "bee sting" induces a measurable nocebo effect that amplifies pain perception compared to positive framing or sensory-focused preparatory information. Furthermore, rigorous analysis confirms that patient satisfaction with the anesthetic procedure is best predicted by the Expectancy Disconfirmation Model, where satisfaction is mathematically derived as the difference between the perception of the event and the pre-procedural expectation. This report provides an exhaustive, evidence-based examination of current methodologies, offering a unified protocol for optimizing clinical communication and technique to enhance patient outcomes
GelInsight: Open-source software for large-sample DNA fragmentation quality control in gel electrophoresis images.
Full text linkHigh throughput DNA fragmentation technology for next generation sequencing have become widely available, but there remains a need for affordable and efficient DNA fragmentation pattern analysis. Commercial electrophoresis platforms, such as the TapeStation, are costly, time-consuming, and have limited batch-processing capabilities. Traditional gel electrophoresis provides a low-cost, high-throughput alternative. However, existing open-source software, such as ImageJ, for gel electrophoresis image analysis typically requires extensive manual pre-processing and yields limited quantitative metrics relevant to DNA fragmentation quality control. Here, we have developed an open-source MATLAB-based software, GelInsight, for bulk analysis of gel electrophoresis images for analysis and quality control of DNA fragmentation patterns. GelInsight integrates automated image and signal processing tools to determine the base pair size distribution of each sample and to calculate key quality control metrics, including multiple peak base pair sizes and base pair size percentage within a specified range. A user-friendly graphical user interface facilitates efficient data interaction and comprehensive visualization of the analytical outputs. The quantification accuracy of GelInsight, including peak base-pair accuracy and relative area measurements, is consistent with both existing open-source software (within 2 ± 2 bp) and commercial assays (within 64 ± 24 bp). Overall, this automated tool streamlines gel image analysis and enhances reproducibility and quantitative rigor in assessing DNA fragmentation patterns
An N-terminal helix of Lsm11 stabilizes CPSF73 in U7 snRNP for histone pre-mRNA 3′-end processing
Full text linkThe U7 snRNP (small nuclear ribonucleoprotein) is responsible for the 3'-end processing of replication-dependent histone messenger RNA precursors (pre-mRNAs). A helix in the Lsm11 N-terminal extension contacts the metallo-β-lactamase domain of the U7 snRNP endonuclease CPSF73. We mutated or deleted this helix and found that the mutant machineries had substantially reduced cleavage activity toward the pre-mRNA. Our cryo-electron microscopy (cryo-EM) studies indicated that the helix was important for helping to hold CPSF73 in its correct position for the cleavage reaction. We also reconstituted a wild-type U7 snRNP in complex with a methylated, noncleavable pre-mRNA. We observed that CPSF73 could achieve an open conformation independent of RNA binding to its active site. Finally, we found that a previously uninterpreted EM density for a small helix at the CPSF73-CPSF100 interface belonged to the C-terminal end of CstF77, copurified from insect cells and highly conserved among CstF77 homologs. This CstF77 binding site had a small effect on the cleavage activity of U7 snRNP. Overall, our studies have revealed the importance of the conserved helix in the Lsm11 N-terminal extension for U7 snRNP, provided structural evidence that CPSF73 can achieve an open, active conformation without RNA binding in its active site, and identified a previously unknown binding site for CstF77 in CPSF100
SAFI-FP Baseline Unannounced Visit User Guide
Full text linkData were collected as part of the baseline for a cluster randomized controlled trial in Kisumu County, Western Kenya, evaluating a social accountability–based quality improvement intervention designed to strengthen contraceptive service delivery through citizen feedback, public monitoring, and dialogue. Baseline data were gathered from all 137 public-sector facilities between May and October 2022 using structured unannounced visits and provider interviews. A very short facility audit was also conducted in between unannounced visits and provider interviews
Social Upgrading in Global Supply Chains: Reframing Corporate Responsibilities
Full text linkMuch philosophical literature on sweatshop ethics assumes that the individual branded marketers that sell consumer goods either employ sweatshop workers or can strongly influence the conditions under which those workers labor. This oversimplification misidentifies the rationale for and details of the responsibilities of big buyers for the labor standards in their supply chains. Throughout this article, we illustrate how philosophers’ “vertical integration” and “control” assumptions distort our understanding of the internal dynamics within supply chains. Under the more realistic assumption that big buyers have “constrained influence” over labor conditions in their supply chains, we show that big buyers retain the responsibility to work toward social upgrading goals. However, fulfilling such a responsibility requires big buyers to collectively cede power to third parties in supply chains in formalized and accountable ways. Recent developments in transnational industrial agreements, such as the International Accord, are examples of this commitment
Differential socioeconomic, psychosocial, and behavioral factors associated with psychological distress and uncontrolled blood pressure among women with and without HIV in the US
Full text linkWomen with HIV (WWH) have a higher risk of hypertension compared to women without HIV (WWoH). Exposure to adverse socioeconomic (e.g., area level deprivation) and psychosocial factors (e.g., stigma, inadequate social support) may contribute to inequities in hypertension through their influence on health behaviors (e.g., substance use, diet, physical activity) and psychophysiological (e.g., stress) responses. We examined the association between socioeconomic and psychosocial factors, psychological distress, and current uncontrolled blood pressure among WWH (n=998) and WWoH (n=353) enrolled in the Women’s Interagency HIV Study (WIHS) at a single visit between April and September 2019. Socioeconomic and psychosocial factors were similar among WWH and WWoH. Among WWH and WWOH, 50.2% had current uncontrolled blood pressure, defined as a systolic blood pressure ≥130 mmHg or diastolic pressure ≥ 80 mmHg at the time of the study visit. Among WWH, socioeconomic, psychosocial, and behavioral factors explained 3% of the variance in blood pressure with self-reported health risk behaviors (r=0.15), and use of antihypertensive medication (r=0.09) had weak to moderate impact. Among WWoH, socioeconomic, psychosocial, and behavioral factors explained 10% of the variance in blood pressure, with self-reported health risk behaviors (r=0.19), use of antihypertensive medication (r=0.19), area-level social vulnerability (r=-0.17), and social support (r=0.16) demonstrating weak to moderate impacts. Tailored interventions that address socioeconomic and psychosocial stressors at the individual and societal levels may improve outcomes and reduce disparities in uncontrolled blood pressure
The Physiology Of the WEight Reduced State (POWERS) study: design and rationale for assessment of food intake, physical activity and other behavioral constructs
Full text linkThe Physiology Of the WEight Reduced State (POWERS) study is a multi-center NIH-funded clinical trial designed to determine the physiological basis for variability in weight loss maintenance among adults with obesity following participation in a behavioral weight loss program. Two hundred and five healthy adults, aged 25–<60 years, with body mass index 30–<40 kg/m2 complete up to four serial assessments (before weight loss; after ≥7% weight loss; and four and 12 months later). This report, one in a five-part series on the POWERS study design, provides the rationale for and description of behavioral measures. Standardized laboratory meals are used to measure energy intake and eating-related behaviors. Behavioral and neurocognitive factors related to eating (e.g., food-choice decision making, taste preferences, reward, self-control) are assessed via computer-based tasks and self-report questionnaires. Functional and structural neuroimaging augment the behavioral assessments by identifying underlying neural circuitry. Psychological factors related to weight regulation (e.g., self-monitoring, stigma, self-efficacy) are assessed via self-report questionnaires. Free-living physical activity and sleep are measured via accelerometry, polysomnography and self-report questionnaires. We will evaluate how changes, integrated values and patterns in these predictors and components of energy intake and energy expenditure contribute to individual variability in weight change during the 12 months following weight loss. We anticipate that extensive phenotyping using sophisticated eating behavior paradigms and assessments of critical components of energy expenditure before and after weight loss will lead to improved predictions of successful weight loss maintenance. This, in turn, will inform more effective treatments for long-term sustained weight loss
Accounting for Exposure Measurement Error in Gridded Air Pollution Estimates in Assessing the Association of PM2.5 Exposures with Health Outcomes in Cohort Studies
Full text linkThere is increasing interest in addressing measurement error in gridded exposure estimates. Here, we provide a framework to account for exposure measurement error in gridded air pollution estimates used for health effects estimation, i.e., when numerical air quality models or satellite-derived data are the principal source of exposure data. We employed a two-stage Bayesian hierarchical modeling framework consisting of an exposure measurement error model and a health model, linking the unobserved true ambient exposure at the residential address for each participant in the cohort to health outcomes. In sensitivity analysis, we considered different health models, spatial smoothing parameters, and spatial resolutions (1.33 and 4 km grid cells) for observation-fused CMAQ output. In an example application, comparison of gridded observation-fused CMAQ estimates and spatially smoothed observation-fused CMAQ estimates by leave-one-out cross-validation at monitoring stations indicated that prediction accuracy at those locations is comparable between the 1.33 km resolution gridded estimates and the smoothed estimates, while the spatially smoothed estimates slightly outperform the 4 km resolution gridded estimates. Accounting for exposure measurement error also resulted in somewhat greater PM2.5 health effect estimates on continuous neuroimaging outcomes and smaller health effect estimates on binary cardiovascular outcomes, although overall conclusions remained similar
Mucociliary and cough clearance in primary ciliary dyskinesia as affected by mutations in RSPH1 or DNAH5
Full text linkBackground Primary ciliary dyskinesia (PCD) is a rare disease caused by mutations in >50 genes that impair the function of motile cilia. The clinical phenotype is heterogeneous and recent studies have begun to investigate genotype–phenotype relationships to better understand disease pathogenesis and develop improved treatments. The major cause of morbidity and mortality among individuals with PCD is the lack of mucociliary clearance (MCC) that results in chronic respiratory infections and leads to bronchiectasis. Here we examine the relationship between MCC and genotype in two groups of PCD individuals; one with mutations in a gene (DNAH5) that causes PCD with mostly immotile cilia and one with mutations in a gene (RSPH1) that cause PCD with cilia that beat with a near-normal frequency, but an abnormal, sometimes circular waveform. Methods Patients with known pathogenic variants in DNAH5 (n=8) or RSPH1 (n=7), along with healthy controls (n=8), were assessed for clearance of an inhaled radioactive tracer by mucociliary and cough clearance as measured by gamma scintigraphy. Results Neither DNAH5 nor RSPH1 subjects showed clear evidence of MCC under either baseline or albuterol stimulated conditions. Unexpectedly, subjects with RSPH1 mutations demonstrated cough clearance (median 9.7%, IQR 6.2–17%) that was significantly higher than subjects with DNAH5 mutations (4.2% (0.94–5.1%); p=0.015) and was not significantly different from healthy control subjects (8.3% (4.2–16%); p=0.88). Conclusions The results confirm impaired MCC in people with PCD of both genotypes. However, in this small cohort, the results suggest cough clearance may differ between these two genotypes.PCD patients with DNAH5 mutations had low levels of both mucociliary and cough clearance; those with mutations in RSPH1 had low levels of mucociliary clearance but, on average, exhibited near-normal levels of cough clearance https://bit.ly/4580Ly
Rehabilitation Referral in Rheumatology: Insights From the RISE Registry
Full text linkObjective The aim was to describe the percentage of patients with axial spondyloarthritis (axSpA), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE) in the Rheumatology Informatics System for Effectiveness (RISE) Registry who received a rehabilitation referral. Methods Data were derived from RISE, an electronic health record enabled registry of approximately 30% of the US clinical rheumatology workforce. Practices were eligible if there was at least one patient record indicating a referral to rehabilitation (physical or occupational therapy) in any plan of care. Patients from eligible practices were included if they were ≥18 years old, had two or more qualifying International Classification of Disease (ICD) codes for axSpA, RA, or SLE at least 30 days apart, and had at least one visit in 2022. The primary outcome was percentage of patients with at least one rehabilitation referral documented in 2022 and at any time, reported by patient and practice characteristics. Results A total of 20,574 adult patients with axSpA, 198,517 with RA, and 37,060 with SLE were identified. In 2022, 4.4%, 2.7%, and 2.6% of patients with axSpA, RA, and SLE were referred to rehabilitation at least once, whereas 11.8%, 9.2%, and 8.7% of these patients received a referral to rehabilitation at any time, respectively. Among practices, 52%, 61%, and 60% of practices referred <1% of patients with axSpA, RA, and SLE to rehabilitation in 2022.ConclusionRehabilitation referral from rheumatology practices was low, with considerable variation across practices. The strength of recommendations for rehabilitation in treatment guidelines seem to have limited impact on referral practices