Benefits Of Reduction Research Articles

Costs and benefits of item reduction: The abridgment of the Emotion Regulation Questionnaire (ERQ)

Shortening existing instruments is a highly required procedure, as short scales may have several advantages over the long versions, especially in time and/or resources restrictions. However, abbreviated forms may be weaker than their parent versions from both content coverage and psychometric robustness. Also, the abridgment of instruments is often lacking in methodological strictness, and the potential drawbacks of the shortened scales are rarely reported. The current study aims to describe the whole process of scale shortening, emphasizing the potential costs and benefits, in terms of balance between time-resource savings and loss of validity and reliability. We shortened the Emotion Regulation Questionnaire (ERQ), involving a sample of 459 participants (53.2% males). Item reduction was driven by searching to preserve the content breadth of the construct and scale's psychometric quality. Our results supported the two-factor structure of the measure (Cognitive Reappraisal and Expressive Suppression), χ2(8) = 11.357 ns, CFI = 0.995, TLI = 0.990, RMSEA = 0.030 (0.000–0.067), SRMR = 0.031, and three items were selected for each subscale. The two intended factors showed good levels of reliability (α > 0.710). A latent variable model was performed to evaluate how the original ERQ and our proposed short version (ERQS) were related to depression, anxiety, and stress: A similar pattern of associations was found, with Cognitive Reappraisal (negatively) and Expressive Suppression (positively) reporting significant but weak associations. The ERQ-S can be beneficial over the original version, as it effectively assesses the two emotion regulation strategies with a trivial loss in reliability and predictive validity.

Clinical Effects of Asynchronous Provider-Guided Practice Sessions During Blended Care Therapy for Anxiety and Depression: Pragmatic Retrospective Cohort Study.

Blended care therapy models are intended to increase the efficiency and effectiveness of evidence-based psychotherapy by combining synchronous and asynchronous components of care. This retrospective cohort study evaluated the clinical effects of synchronous video therapy sessions and asynchronous guided practice session elements on anxiety and depression in a blended care therapy program, with a novel focus on asynchronous provider feedback messages. Participants were adults (N=33,492) with clinical symptoms of anxiety (Generalized Anxiety Disorder 7-item scale [GAD-7] score of ≥8) and depression (Patient Health Questionnaire 9-item scale [PHQ-9] score of ≥10) at intake. Symptom trajectories were evaluated via individual growth curve models. Time-varying covariates evaluated effects of synchronous video session attendance and the presence or absence of each asynchronous guided practice session element occurring within 7 days and 8-14 days prior to each clinical outcome assessment. Guided practice session elements included client digital lesson completion, client digital exercise completion, and feedback messages sent by providers. Approximately 86.6% (29,012/33,492) of clients met criteria for clinical improvement by end of care (median 6, IQR 4-8 synchronous sessions). Synchronous video session attendance and client digital lesson completion in the past 7 days and in the past 8-14 days were each uniquely and significantly associated with lower GAD-7 scores (video session effects: bsession7=-0.82, bsession8-14=-0.58, P values<.001; digital lesson effects: blesson7=-0.18, blesson8-14=-0.26, P values <.001) and PHQ-9 scores (video session effects: bsession7=-0.89, bsession8-14=-0.67, P values <.001; digital lesson effects: blesson7=-0.12, blesson8-14=-0.30, P values <.001). Client digital exercise completion in the past 8-14 days was significantly associated with lower GAD-7 scores (bexercise8-14=-0.10; P<.001) but exercise completion in the 7 days prior to clinical outcome assessment was not (bexercise7=0.00; P=.89). Exercise completion in the past 7 days was significantly associated with lower PHQ-9 scores (bexercise7=-0.16; P<.001) but exercise completion in the past 8-14 days was not (bexercise8-14=-0.05; P=.09). Provider feedback messaging in the past 7 days and in the past 8-14 days was significantly associated with lower GAD-7 and PHQ-9 scores, respectively (GAD-7: bfeedback7=-0.12, P<.001; bfeedback8-14=-0.07, P=.004; PHQ-9: bfeedback7=-0.15, P<.001; bfeedback8-14=-0.08, P=.01). Provider feedback between synchronous therapy sessions provided significant benefit for symptom reduction, beyond the effects of client digital engagement and synchronous video sessions. When guided practice sessions are well integrated into care, blended care therapy provides meaningful improvements upon the traditional, synchronous session-only therapy model. Provider guidance and feedback for clients between synchronous sessions support more efficient and effective mental health care overall.

Improving Productivity and Reducing Costs in an IT Service Provider: Applying the Lean Six Sigma Methodology

Objective: to present the use of the Six Sigma framework as a framework for IT Governance, in a multinational company that operates in the market of IT outsourcing services, with a view to assisting in the improvement of productivity, in its consequent significant reduction of costs and a better operational performance in the processes of the company providing outsourced IT services. Theoretical Framework: The study addresses concepts of the Lean philosophy, as well as the Six Sigma framework and the marriage of Lean and Six Sigma as a way to obtain advantages from the application of its methods, meeting the needs of the organization. Method: In this study, quantitative and qualitative methods were used from a descriptive research. A literature review and associated issues were carried out and a case study was applied from the results obtained through a project in a large multinational company that provides IT outsourcing services. Outcome and Discussion: The combination of Six Sigma with the business process offered the company an opportunity for cost reduction and improved its competitive advantage in an increasingly competitive and quality-driven market. Regarding the implementation of the incident governance process, a reduction of 24% was obtained; Regarding actions to reduce the number of overtime, a reduction of 40% was obtained. A total monthly reduction of US$ 5,589 was obtained and annually the reduction amount plus benefits reached US$ 67,068. Research Implications: Research contributes to the improvement of quality and significant cost reduction with the application of the Six Sigma framework, properly tested and demonstrated in an organization. Originality/Value: This study contributes to the literature by using the Six Sigma framework as a framework for IT Governance in order to help improve productivity with consequent significant cost reduction and better operational performance in the processes of an outsourced IT service provider. The relevance and value of this research are evidenced by the demonstration of the benefits obtained in the environment of the company under analysis.

Effects of glucagon-like peptide-1 receptor agonists on blood pressure in overweight or obese patients: a meta-analysis of randomized controlled trials.

Glucagon-like peptide-1 receptor agonists are novel medications with proven efficacy in treating type 2 diabetes mellitus, and are increasingly being used for weight loss. They may potentially have benefit in treating metabolic disorders; however, evidence is sparse with regards to treating high blood pressure (BP). We performed a systematic review, meta-analysis and meta-regression investigating the efficacy of GLP-1 RAs in lowering BP in obese or overweight patients. Three electronic databases (PubMed, EMBASE, and CENTRAL) were systematically searched for randomized controlled trials (RCTs) published from inception to 13 February 2024. Pair-wise meta-analysis and random effects meta-regression models were utilized. Fixed effects meta-regression was used to unify treatment effects across different GLP-1 RA doses. We included a total of 30 RCTs with a combined population of 37 072 patients. GLP-1 RAs demonstrated a mean systolic BP (SBP) reduction of -3.37 mmHg [95% confidence interval (CI) -3.95 to -2.80] and a mean diastolic BP (DBP) reduction of -1.05 mmHg (95% CI -1.46 to -0.65) compared with placebo. This effect was consistent across subgroups for diabetic status, formulation of GLP-1 RA, follow-up duration and route of administration for both SBP and DBP, with the exception of subgroups investigating exenatide. Meta-regression suggested no significant correlation between BP reduction and baseline characteristics such as age, percentage of male patients, HbA1c, weight, BMI, and percentage of patients with hypertension. Our meta-analysis suggests significant BP reduction benefits from GLP-1 RA use in obese or overweight patients, consistent across diabetic status, duration of treatment, and across route of administration.

Effects of Different Land Uses and Slope on Runoff and Soil Loss on the Loess Plateau of China

ABSTRACTThe Loess Plateau has one of the most serious areas of soil erosion in China; therefore, studying the effect of soil and water conservation measures on the erosion of loess soil slopes is important for land management and agricultural development. This study is based on 5 years of field runoff observations and rainfall data from 2015 to 2019. Correlation and regression analyses were used to study the runoff and sediment production of loess soil and its relationship with rainfall, slope and land use. The results show that &gt; 80% of the erosive rainfall occurs mainly in July to August in the area. Runoff and soil loss from the plots differed substantially, depending on land use, soil conservation measures and slope degree. Bare plots experienced the highest soil loss rate of over 27 t/ha with higher runoff depth, followed by cultivated plots (4.55 t/ha), grass plots (0.43 t/ha), shrub plots (0.35 t/ha) and forest plots (0.13 t/ha). Among the four soil and water conservation measures, the runoff and sediment reduction benefits of forest and shrub plots were the highest. The runoff reduction benefit fluctuated at approximately 0.8, and the benefit of sediment reduction was ≈1. The overall performance was forest &gt; shrubland &gt; grassland &gt; cultivated land &gt; bare land, and the benefits of sediment reduction were greater than those of runoff reduction. Forests had the highest soil retention capacity on slopes from 5° to 25°, and forests on gentle slopes had the best water storage capacity. Shrub plots had the best water storage capacity when they were on steep slopes. Rainfall erosion forces were significantly and positively correlated (p &lt; 0.01) with runoff depth and soil loss, making it the most significant rainfall indicator of sediment production. Under the same rainfall conditions, soil and water conservation measures are still required on bare slopes, land use is the main control factor for slope sediment production, and appropriate land use can greatly reduce the threat of slopes in terms of soil erosion. This study shows that soil and water conservation measures are imperative to prevent runoff and soil loss, especially for bare land without any measures; on steep slopes, a vegetation combination primarily featuring shrubs is expected to achieve greater benefits in reducing runoff and sediment. This study can provide a scientific basis for the management of vegetation measures and the implementation of soil and water conservation measures on loess soil slopes.

A Gastronomic Approach to Industrial Aquaculture Waste Utilization

Aquaculture, while offering significant contributions to global food security, generates substantial amounts of industrial waste, posing environmental and economic challenges. However, this waste also presents untapped potential for innovation in gastronomy. This paper explores the emerging trend of utilizing aquaculture industrial wastes in culinary practices, aiming to reduce waste, promote sustainability, and create novel gastronomic experiences. Through a review of literature and case studies, we examine various methods for repurposing aquaculture waste, including upcycling into new food products, incorporation into culinary dishes, and extraction of valuable components. Additionally, we highlight successful initiatives that have integrated aquaculture waste into gastronomy, emphasizing the benefits of waste reduction, sustainable food practices, and culinary innovation. Challenges such as food safety, taste, and consumer acceptance are acknowledged, with strategies proposed for addressing these issues. Finally, we discuss future directions for research and development in this field, identifying opportunities for collaboration between the aquaculture industry and the gastronomy sector. By exploring the utilization of aquaculture industrial wastes in gastronomy, this paper contributes to a deeper understanding of sustainable food practices and culinary creativity in the context of aquaculture waste management.

Impact and mechanisms of high-speed rail construction on carbon emissions: A quasi-natural experiment in China

Carbon emissions present a significant climate challenge for China. As a major source of these emissions, reducing transportation-related carbon output is essential to achieving the country's dual carbon goals. In this context, high-speed rail (HSR) emerges as a green, low-carbon alternative with an increasingly significant role in reducing carbon emissions. This paper explores the impact of HSR station construction on carbon emissions using data from 248 prefecture-level cities from 2003 to 2019, treating the construction as a quasi-natural experiment. Employing a spatial DID model, the research investigates how HSR construction affects carbon emission intensity within the region and in neighboring areas. It also considers socioeconomic factors to understand their mediating roles. The findings reveal that HSR construction significantly reduces regional carbon emissions over time, with long-term and gradually increasing effects. Spatially, HSR also has substantial spillover effects in reducing carbon emissions in adjacent regions. Numerically, HSR reduces carbon emissions by an average of 1.7% in the local region and 2.3% in the surrounding areas. The mechanism analysis indicates that the carbon reduction benefits of HSR stem from a complex interplay of multiple factors, with each selected factor playing a partial mediating role. Notably, the concentration of human capital and the flow of innovation are crucial pathways for regional carbon reduction. However, despite HSR's promotion of industrial structure upgrades and substitution of traditional transportation, these factors have not yet significantly contributed to carbon reduction under current conditions. These results underscore the critical position of HSR in carbon reduction and provide a theoretical foundation for future HSR planning and sustainable development policy formulation.

ORIENTAÇÃO FARMACÊUTICA E OS RISCOS DA SEMAGLUTIDA: NAVEGANDO COM SEGURANÇA NA PERDA DE PESO

The overall objective is to understand the adverse effects and dangers associated with the inappropriate use of these medications, as well as the importance of professional guidance for safe weight loss. The methodology adopted was an integrative literature review, with searches in the LILACS and SCIELO databases, between 2019 and 2024, using terms such as “use”, “medication” and “weight loss”. Inclusion criteria were articles relevant to the topic, published in Portuguese and available in full. Editorials, reports and bulletins were excluded. In development, the study addresses obesity as a multifactorial condition, commonly associated with an energy imbalance. It discusses the use of semaglutide, a medication used off-label for weight loss, highlighting its mechanisms of action, efficacy and side effects. It is concluded that, despite the benefits in weight reduction, the indiscriminate use of semaglutide without medical guidance can lead to serious complications. Pharmacists play an essential role in guiding patients on the safe use of these medications, promoting an integrated and safe approach to weight loss. The study emphasizes the importance of responsible and informed practices for managing obesity, preventing risks to physical and mental health.

Manufacturing and mechanical performance of lightened gypsum reinforced by hemp/epoxy composites

In recent years, the construction industry has increasingly focused on reducing its environmental impact, addressing research efforts towards innovative materials and technological solutions. In this context, gypsum-based materials and natural fibers represent some of the most promising alternatives in terms of sustainability. This paper aims to propose a new gypsum structure reinforced with a composite hemp fabric impregnated with epoxy resin, investigating its manufacturing process and the mechanical properties, specifically in terms of flexural, impact and bearing strength. To achieve lightweight structures, lightened gypsum was also considered in addition to conventional gypsum. Both the lightened gypsum matrix and the hemp/epoxy reinforcement were produced using specific techniques able to obtain lightweight gypsum composites. Beneficial effects in the use of lightened gypsum matrix were found indeed, the reinforced lightweight samples exhibited higher values of flexural strength coupled with a density reduction of about 18%. Additionally, a significant change in post-cracking behavior was observed, with a gradual failure rather than a brittle one. The same trend was observed for the impact, while for bearing strength, the presence of porosity affected negatively the resistance of the composites, prevailing over the benefits of density reduction. Experimental results demonstrated the presence of a good interaction between the hemp fabric and the gypsum matrix, which was further confirmed by the microstructure analysis. The interesting mechanical properties showed by these lightweight gypsum/hemp composites, suggested their possible use for different and unconventional applications of gypsum-based walls and components.

Interface misfit of conventionally milled and novel hybrid full-arch implant-supported titanium frameworks

ObjectiveA hybrid manufacturing technique that combines selective laser melting (SLM) and computer numerical control (CNC) has been developed for the fabrication of implant-platform/framework interfaces (PFIs) for mandibular and maxillary full-arch implant-supported titanium frameworks. The aim of this study was to compare the discrepancies in specimens fabricated using the hybrid technique (termed SLM/m hereafter) with those in specimens fabricated by conventional CNC milling.Materials and methodsBased on a mandibular four-PFI CAD model and a maxillary six-PFI CAD model, four groups of titanium frameworks (eight per group, totaling 32) were fabricated according to the fabrication technique (SLM/m or milling) and number of PFIs (four or six). The frameworks were scanned by a structured light scanner and aligned with the CAD model in Geomagic Control X. Discrepancy was defined as the difference between the PFIs of the scanned framework and those of the CAD model. Discrepancies were measured and evaluated by multilevel analysis using a mixed-effects model (α = 0.05), followed by independent samples t-tests (α = 0.0125). Furthermore, the manufacturing times and raw-material costs were recorded and compared.ResultsThe maximum discrepancy values for the four-PFI and six-PFI hybrid frameworks were 52.2 and 64.3 μm, respectively. Multilevel analysis revealed that the fabrication technique and the number of PFIs had no significant effect on the discrepancy value. However, a significant interaction between the two factors was observed (P = 0.020). The discrepancies for the four-PFI hybrid frameworks were significantly lower than those for the four-PFI milled frameworks (P = 0.001). No significant difference in discrepancies between the six-PFI hybrid frameworks and six-PFI milled frameworks was observed (P = 0.697). Furthermore, the hybrid frameworks required only 11% of the raw materials and 25% of the milling time required for the conventionally milled frameworks.ConclusionSLM/m hybrid frameworks are viable, accurate alternatives to CNC-milled frameworks, with the added benefit of substantial cost reduction.

Current Scenario and Global Perspective of Sustainable Algal Biofuel Production.

Industrialization and globalization have increased the demand for petroleum products that has increased a load on natural energy resources. The escalating fossil fuel utilization has resulted in surpassing the Earth's capacity to absorb greenhouse gases, necessitating the exploration of sustainable bioenergy alternatives to mitigate emissions. Biofuels, derived from algae, offer promising solutions to alleviate fossil fuel dependency. Algae, often regarded as third-generation biofuels, present numerous advantages owing to their high biomass production rates. While algae have been utilized for their bioactive compounds, their capability as biomass for the production of biofuel has gained traction among researchers. Various biofuels such as bio-hydrogen, bio-methane, bio-ethanol, bio-oil, and bio-butanol can be derived from algae through diverse processes like fermentation, photolysis, pyrolysis, and transesterification. Despite the enormous commercial potential of algae-derived biofuels, challenges such as high cultivation costs persist. However, leveraging the utilization of algae byproducts could improve economic viability of biofuel production. Moreover, algae derived biofuels offer environmental sustainability, cost-effectiveness, and waste reduction benefits, promising novel opportunities for a more sustainable energy future.

Blood Pressure Reduction and Changes in Antihypertensive Medication Use Among Patients With Hypertension Who Initiated Sodium-Glucose Cotransporter-2 Inhibitors.

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated a blood pressure (BP) reduction benefit despite other indications for use. We evaluated BP changes and antihypertensive medication use pre- and post-SGLT2i initiation among 12 960 patients with treated hypertension and among subgroups with apparent treatment-resistant hypertension (aTRH) and/or proteinuria. Post-SGLT2i initiation, the mean (SD) systolic blood pressure (SBP) was reduced from 133.9 (16.4) to 128.6 (15.5) mmHg and the mean diastolic blood pressure (DBP) was reduced from 70.8 (11.8) to 68.3 (11.3) mmHg among all patients. The mean SBP/DBP reduction was 5.3/2.5, 6.2/2.8, and 6.1/2.9mmHg among all patients, patients with aTRH, and patients with proteinuria, respectively. Achieved BP < 130/80mmHg increased by 12.5%, 16.9%, and 11.1% for all patients, patients with aTRH, and patients with proteinuria, respectively. Discontinuation of ≥ 1 antihypertensive medication within 12 months of SGLT2i initiation occurred in 33.4% overall, 47.6% of patients with aTRH, and 38.7% of patients with proteinuria.

An Evaluation of the Sediment Reduction Benefits of Soil and Water Conservation Measures under Extreme Rainfall Conditions in the Loess Plateau in China Based on a Distributed Soil Erosion Model

Since the 1970s, comprehensive control measures on soil erosion in the headwater region of the Loess Plateau have been carried out. Quantitative evaluation of the benefits of soil and water conservation measures during extreme rainstorms is of great significance for the comprehensive management of the catchments. In this study, a systematic modeling methodology for evaluating the effects of soil and water conservation measures on sediment reduction was developed based on a distributed soil erosion model (DSEM). Taking the Chabagou basin in the Loess Plateau as the study area, the tested DSEM was used to simulate soil erosion and sediment yield during an extreme rainstorm under two scenarios, the uncontrolled condition and the controlled condition with soil and water conservation measures implemented. The results showed that DSEM could successfully simulate soil and water losses and evaluate the effects of soil and water conservation measures during extreme storm events. The evaluated results showed that each soil and water conservation measure had the specific function of sediment reduction. And under rainstorm conditions, the effect of engineering measures on sediment reduction was greater than that of forest and grass measures.

The ECP ALPINE project: In situ and post hoc visualization infrastructure and analysis capabilities for exascale

A significant challenge on an exascale computer is the speed at which we compute results exceeds by many orders of magnitude the speed at which we save these results. Therefore the Exascale Computing Project (ECP) ALPINE project focuses on providing exascale-ready visualization solutions including in situ processing. In situ visualization and analysis runs as the simulation is run, on simulations results are they are generated avoiding the need to save entire simulations to storage for later analysis. The ALPINE project made post hoc visualization tools, ParaView and VisIt, exascale ready and developed in situ algorithms and infrastructures. The suite of ALPINE algorithms developed under ECP includes novel approaches to enable automated data analysis and visualization to focus on the most important aspects of the simulation. Many of the algorithms also provide data reduction benefits to meet the I/O challenges at exascale. ALPINE developed a new lightweight in situ infrastructure, Ascent.

Duloxetine for individuals with chronic back pain: A systematic review and meta‑analysis of randomized controlled trials.

The current study aimed to assess the efficacy of duloxetine in reducing pain and improving the quality of life of individuals with chronic low back pain (CLBP). An extensive literature search was conducted to identify relevant studies that examined the efficacy of duloxetine in CLBP management. The primary objective of the present study was to assess the role of duloxetine use on pain levels, as well as improvements in quality of life, using validated instruments. The results were synthesized using a random-effects model. A total of 8 studies were included in the analysis. Duloxetine demonstrated clear benefits in pain reduction, evidenced by improvements across multiple scales including the visual analogue scale, brief pain inventory-interference (BPI), BPI-severity, weekly worst pain over 24 hours and Roland-Morris Disability Questionnaire scores. Quality of life improved with duloxetine treatment, as indicated by the 36-item short form survey (SF-36). However, there was no significant impact on the physical function component of SF-36. The present study provides evidence to affirm the efficacy of duloxetine in treating CLBP. Further research is required to validate these findings and to establish whether combining duloxetine with other CLBP treatments yields superior outcomes.

Flavokavains A- and B-Free Kava Enhances Resilience against the Adverse Health Effects of Tobacco Smoke in Mice.

Tobacco smoke remains a serious global issue, resulting in serious health complications, contributing to the onset of numerous preventive diseases and imposing significant health burdens. Despite regulatory policies and cessation measures aimed at curbing its usage, novel interventions are urgently needed for effective damage reduction. Our preclinical and pilot clinical studies showed that AB-free kava has the potential to reduce tobacco-smoking-induced lung cancer risk, mitigate tobacco dependence, and reduce tobacco use. To understand the scope of its benefits in damage reduction and potential limitations, this study evaluated the effects of AB-free kava on a panel of health indicators in mice exposed to 2-4 weeks of daily tobacco smoke exposure. Our assessments included global transcriptional profiling of the lung and liver tissues, analysis of lung inflammation, evaluation of lung function, exploration of tobacco nicotine withdrawal, and characterization of the causal protein kinase A (PKA) signaling pathway. As expected, tobacco smoke exposure perturbed a wide range of biological processes and compromised multiple functions in mice. Remarkably, AB-free kava demonstrated the ability to globally mitigate tobacco smoke-induced deficits at the molecular and functional levels with promising safety profiles, offering AB-free kava unique promise to mitigate tobacco smoke-related health damages. Further preclinical evaluations are warranted to fully harness the potential of AB-free kava in combating tobacco smoke-related harms in the preparation of its clinical translation.

Longitudinal Assessment of Transfusion Intensity in Patients With JAK Inhibitor–Naive or –Experienced Myelofibrosis Treated With Momelotinib

PurposeAnemia is a cardinal feature of myelofibrosis often managed with red blood cell (RBC) transfusions, which may contribute to negative prognostic, quality-of-life, and healthcare-related economic impacts. The Janus kinase (JAK) 1/JAK2/activin A receptor type 1 inhibitor momelotinib was approved for the treatment of patients with myelofibrosis and anemia based on clinical trial evidence of anemia, spleen, and symptom benefits illustrated using binomial response/nonresponse endpoints. In the present post hoc, descriptive analyses, the impact of momelotinib on RBC transfusion burden over time was further characterized across JAK inhibitor–naive and –experienced patients. MethodsAll RBC units transfused were collected during the baseline and 24-week treatment periods, initially in a single-arm phase 2 study as proof-of-concept analysis, and then versus comparators (ruxolitinib, best available therapy [BAT], and danazol) in the phase 3 SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM studies, respectively. ResultsIn the phase 2 study, mean transfusion requirement changed by −1.5 units/28 days, with 85% of patients (35/41) achieving numeric transfusion reduction. Across SIMPLIFY-1, SIMPLIFY-2, and MOMENTUM, mean transfusion requirements decreased with momelotinib (−0.1, −0.36, and −0.86 units/28 days), while mean requirements with ruxolitinib, BAT, and danazol changed by +0.39, 0, and ‒0.28 units/28 days, respectively. Overall, 87% (185/213), 77% (79/103), and 85% (110/130) of patients had improved or stable transfusion intensities with momelotinib versus 54% (117/216), 62% (32/52), and 63% (41/65) with ruxolitinib, BAT, and danazol. ConclusionThese novel time-dependent transfusion burden analyses demonstrate that momelotinib is associated with anemia-related benefits in most patients and greater transfusion burden reduction versus comparators. Trial registrationClinicalTrials.gov identifiers: NCT02515630, NCT01969838, NCT02101268, NCT04173494.

In dystrophic mdx hindlimb muscles where fibrosis is limited, versican haploinsufficiency transiently improves contractile function without reducing inflammation.

Versican is increased with inflammation and fibrosis, and is upregulated in Duchenne muscular dystrophy. In fibrotic diaphragm muscles from dystrophic mdx mice, genetic reduction of versican attenuated macrophage infiltration and improved contractile function. Versican is also implicated in myogenesis. Here, we investigated whether versican modulated mdx hindlimb muscle pathology, where inflammation and regeneration are increased but fibrosis is minimal. Immunohistochemistry and qRT-PCR were used to assess how fiber type and glucocorticoids (α-methylprednisolone) modify versican expression. To genetically reduce versican, female mdx and male versican haploinsufficient (hdf) mice were bred resulting in male mdx-hdf and mdx (control) pups. Versican expression, contractile function, and pathology were evaluated in hindlimb muscles. Versican immunoreactivity was greater in slow versus fast hindlimb muscles. Versican mRNA transcripts were reduced by α-methylprednisolone in soleus, but not in fast extensor digitorum longus, muscles. In juvenile (6-wk-old) mdx-hdf mice, versican expression was most robustly decreased in soleus muscles leading to improved force output and a modest reduction in fatiguability. These functional benefits were not accompanied by decreased inflammation. Muscle architecture, regeneration markers, and fiber type also did not differ between mdx-hdf mice and mdx littermates. Improvements in soleus contractile function were not retained in adult (20-wk-old) mdx-hdf mice. In conclusion, soleus muscles from juvenile mdx mice were most responsive to pharmacological or genetic approaches targeting versican; however, the benefits of versican reduction were limited due to low fibrosis. Preclinical matrix research in dystrophy should account for muscle phenotype (including age) and the interdependence between inflammation and fibrosis. NEW & NOTEWORTHY The proteoglycan versican is upregulated in muscular dystrophy. In fibrotic diaphragm muscles from mdx mice, versican reduction attenuated macrophage infiltration and improved performance. Here, in hindlimb muscles from 6- and 20-wk-old mdx mice, where pathology is mild, versican reduction did not decrease inflammation and contractile function improvements were limited to juvenile mice. In dystrophic mdx muscles, the association between versican and inflammation is mediated by fibrosis, demonstrating interdependence between the immune system and extracellular matrix.

Health benefits of air pollution reduction: Evidence from economic slowdown in India

This paper evaluates health benefits associated with the impact of air pollution reduction on infant mortality in India. Leveraging plausibly exogenous geographic variation in air pollution due to the post-2010 economic slowdown—a period largely overlooked in the literature—I find that improvements in air quality resulted in a significant decline in infant mortality, particularly through respiratory diseases and biological pathways such as in utero and post-birth exposure. The associated health benefits correspond to 1338 saved infant lives, translating to monetary gains of $312.5 million. The paper advances our understanding of the link between air pollution and human health in settings with elevated air pollution and suboptimal regulatory frameworks.

Review on the role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway in diabetes: mechanistic insights and therapeutic implications.

This review explores the pivotal role of the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome in the pathogenesis of diabetes and its complications, highlighting the therapeutic potential of various oral hypoglycemic drugs targeting this pathway. NLRP3 inflammasome activation, triggered by metabolic stressors like hyperglycemia, hyperlipidemia, and free fatty acids (FFAs), leads to the release of pro-inflammatory cytokines interleukin-1β and interleukin-18, driving insulin resistance, pancreatic β-cell dysfunction, and systemic inflammation. These processes contribute to diabetic complications such as nephropathy, neuropathy, retinopathy, and cardiovascular diseases (CVD). Here we discuss the various transcriptional, epigenetic, and gut microbiome mediated regulation of NLRP3 activation in diabetes. Different classes of oral hypoglycemic drugs modulate NLRP3 inflammasome activity through various mechanisms: sulfonylureas inhibit NLRP3 activation and reduce inflammatory cytokine levels; sodium-glucose co-transporter 2 inhibitors (SGLT2i) suppress inflammasome activity by reducing oxidative stress and modulating intracellular signaling pathways; dipeptidyl peptidase-4 inhibitors mitigate inflammasome activation, protecting against renal and vascular complications; glucagon-like peptide-1 receptor agonists attenuate NLRP3 activity, reducing inflammation and improving metabolic outcomes; alpha-glucosidase inhibitors and thiazolidinediones exhibit anti-inflammatory properties by directly inhibiting NLRP3 activation. Agents that specifically target NLRP3 and inhibit their activation have been identified recently such as MCC950, Anakinra, CY-09, and many more. Targeting the NLRP3 inflammasome, thus, presents a promising strategy for managing diabetes and its complications, with oral hypoglycemic drugs offering dual benefits of glycemic control and inflammation reduction. Further research into the specific mechanisms and long-term effects of these drugs on NLRP3 inflammasome activity is warranted.