Subset Of Population Research Articles

Human Dendritic Cell Differentiation in Hematopoietic Stem Cell-Transplanted NOG hFLT3L Tg/mFlt3 KO Humanized Mice

Human immune system-reconstituted humanized mice are useful animal models to study human immunology in vivo. Human hematopoietic stem cell-transferred NOG mice are well recognized as humanized immune system models with reconstitution of mature lymphoid lineage cells such as T and B cells. However, human myeloid lineage cells including dendritic cells (DCs) do not fully differentiate in conventional NOG mice. DCs play a crucial role in adaptive immunity through antigen presentation to T cells to acquire antigen specificity. In this study, we established a novel humanized mouse with human DC differentiation. To induce DCs, we generated human Fms-like tyrosine kinase 3 ligand (hFLT3L) transgenic NOG (hFLT3L-Tg) mice and transferred human CD34+ hematopoietic stem cells (HSC) into them. Unexpectedly, low frequency of human cell engraftment was observed in the hFLT3L-Tg mice after HPC reconstitution. In the Tg mice, mouse CD11b+Gr1− myeloid cells were markedly expanded in the bone marrow due to the cross-reaction between hFLT3L and mouse Flt3 receptor, and these myeloid leukemia-like cells interfered with the engraftment of human hematopoietic cells in hFLT3L-Tg mice. To avoid this cross-reaction, we further generated NOG FLT3 receptor KO (mFlt3 KO) mice by CRISPR/Cas9 technique, and the KO mice combined with hFLT3L Tg mice to create hFLT3L Tg/mFlt3 KO (FL Tg/KO) mice. Mouse CD11b+Gr1− leukemia-like cells did not proliferate in FL Tg/KO mice due to blockade of the FLT3 signals in mouse leukocytes. After human HSC transplantation, human CD45+ cells were successfully engrafted in FL Tg/KO mice. Furthermore, major subsets of human DC populations, cDC1, cDC2, and pDC, and skin Langerhans cells were significantly differentiated in FL Tg/KO mice. Therefore, these humanized mouse models are potentially valuable in the investigation of DC-mediated human adaptive immune responses in vivo.

DNAR-12. STEAROYL-COA DESATURASE REGULATES DNA DAMAGE REPAIR IN GBM BY MODULATING PARP1 ACTIVITY

Abstract Glioblastoma (GBM) is the most prevalent malignant brain cancer in adults, notorious for its aggressiveness and resistance to therapy. GBM patients commonly receive radiation therapy combined with temozolomide (TMZ), which engages tumor cells to promote lethal DNA damage and subsequent cytotoxicity. Active DNA repair mechanisms, particularly in a subset population of GBM stem-like cells (GSCs), drive therapeutic resistance, thus largely contributing to the bleak prognosis of GBM. Poly (ADP-ribose) polymerases (PARPs) are essential in various cellular processes, including DNA repair. We have previously reported that fatty acid desaturation mediated by Stearoyl-CoA desaturase 1 (SCD1) plays a cytoprotective role in GSCs. Inhibiting SCD prevents tumor initiation and inhibits DNA damage repair, hence sensitizing to radiation and TMZ. Yet, the mechanistic role of SCD in DNA damage regulation remained unknown. Here, we found that the expression of both human isoforms of SCD, SCD1, and SCD5, directly correlates with PARP protein levels and subcellular localization. Downregulating SCD1/5 in GSCs resulted in significantly lower levels of PARP1, coupled with increased DNA damage, as well as reduced DNA damage repair and chromosome assembly. Conversely, cells overexpressing SCD1/5 exhibited higher PARP1 expression and lower levels of basal DNA damage compared to control GSCs. Notably, SCD1/5 overexpression also led to increased resistance to TMZ. We show that SCD1/5 regulates PARP activity by controlling PARP1 subcellular localization. In addition to decreased total levels of PARP following SCD1/5 downregulation, we also found increased PARP1 self-PARylation. Using confocal microscopy, we show that when SCD1/5 is repressed, PARylated PARP translocates from the nucleus to the cytosol, rendering it unable to bind DNA and recruit DNA-repairing machinery. In conclusion, our study provides a direct link between fatty acid metabolism and PARP1-mediated DNA damage repair.

Outside the Western bubble: Explaining anti‐immigrant attitudes in 28 post‐communist countries

AbstractMost studies on anti‐immigrant attitudes have been conducted within the US or in Western European countries. As a result, the theoretical frameworks utilised to comprehend these attitudes are often based on a limited subset of the global population. Hence, it remains uncertain how these theories apply to regions beyond the Western context. Based on the Life in Transition Survey, we explore whether the theories and factors discussed in Western contexts can be applied to understanding anti‐immigrant attitudes in 28 post‐communist countries. We find that the impact of macroeconomic variables in the post‐communist region differs from what would be expected based on existing theoretical frameworks. The study adds complexity to the debates surrounding the positive impacts of modernisation, economic development and democratisation on anti‐immigrant attitudes. Our research suggests that intolerance levels are notably highest in Central and Eastern European EU countries. Interestingly, these levels are higher than those found in less developed and less democratic post‐communist countries outside the EU. This study highlights the difficulty of deploying a comprehensive theoretical framework that can account for the complexities of attitudes across a broad range of countries.

Air–Bone Gap in Meniere’s Disease: A Case Series and Literature Review

Background/Objectives: An air–bone gap (ABG) on audiometry is usually secondary to a conductive hearing loss. However, persistent and repeatable ABGs on audiometry in the absence of external or middle ear pathology is thought to arise from inner ear disorders including Meniere’s Disease (MD). In this paper, we aim to showcase this interesting finding occurring in MD with an associated literature review. Methods: Using retrospective review and analysis of case notes, we describe eight cases of persistent ABG on audiometry in MD. All other causes for the ABG were explored and excluded with the aid of objective audiological testing. Results: ABG can occur in a small sub-set of the MD population. In our case series, the ABG was typically found to affect the low frequencies. Higher frequencies appear to be spared. However, a detailed history, examination and battery of objective tests are required to ensure that all other causes of the ABG are reliably considered and excluded prior to attributing it to the inner ear. The finding of an ABG in MD may be dependent on the stage of the disease. Further research is required to determine the underlying cause of the ABG and its potential applications to help guide treatment.

The geometry of correlated variability leads to highly suboptimal discriminative sensory coding.

The brain represents the world through the activity of neural populations; however, whether the computational goal of sensory coding is to support discrimination of sensory stimuli or to generate an internal model of the sensory world is unclear. Correlated variability across a neural population (noise correlations) is commonly observed experimentally, and many studies demonstrate that correlated variability improves discriminative sensory coding compared to a null model with no correlations. However, such results do not address whether correlated variability is for discriminative sensory coding. If the computational goal of sensory coding is discriminative, then correlated variability should be optimized to support that goal. We assessed optimality of noise correlations for discriminative sensory coding in diverse datasets by developing two novel null models, each with a biological interpretation. Across datasets, we found correlated variability in neural populations leads to highly suboptimal discriminative sensory coding according to both null models. Furthermore, biological constraints prevent many subsets of the neural populations from achieving optimality, and subselecting based on biological criteria leaves discriminative coding performance suboptimal. Finally, we show that optimal subpopulation are exponentially small as the population size grows. Together, these results demonstrate that the geometry of correlated variability leads to highly suboptimal discriminative sensory coding.

Iterative random forest-based identification of a novel population with high risk of complications post non-cardiac surgery

Assessing the risk of postoperative cardiovascular events before performing non-cardiac surgery is clinically important. The current risk score systems for preoperative evaluation may not adequately represent a small subset of high-risk populations. Accordingly, this study aimed at applying iterative random forest to analyze combinations of factors that could potentially be clinically valuable in identifying these high-risk populations. To this end, we used the Japan Medical Data Center database, which includes claims data from Japan between January 2005 and April 2021, and employed iterative random forests to extract factor combinations that influence outcomes. The analysis demonstrated that a combination of a prior history of stroke and extremely low LDL-C levels was associated with a high non-cardiac postoperative risk. The incidence of major adverse cardiovascular events in the population characterized by the incidence of previous stroke and extremely low LDL-C levels was 15.43 events per 100 person-30 days [95% confidence interval, 6.66–30.41] in the test data. At this stage, the results only show correlation rather than causation; however, these findings may offer valuable insights for preoperative risk assessment in non-cardiac surgery.

Prediction and clustering of Alzheimer’s disease by race and sex: a multi-head deep-learning approach to analyze irregular and heterogeneous data

Early detection of Alzheimer’s disease (AD) is crucial to maximize clinical outcomes. Most disease progression analyses include people with diagnoses of cognitive impairment, limiting understanding of AD risk among those with normal cognition. The objective was to establish AD progression models through a deep learning approach to analyze heterogeneous, multi-modal datasets, including clustering analyses of population subsets. A multi-head deep-learning architecture was built to process and learn from biomedical and imaging data from the National Alzheimer’s Coordinating Center. Shapley additive explanation algorithms for feature importance ranking and pairwise correlation analysis were used to identify predictors of disease progression. Four primary disease progression clusters (slow, moderate and rapid converters or non-converters) were subdivided into groups by race and sex, yielding 16 sub-clusters of participants with distinct progression patterns. A multi-head and early-fusion convolutional neural network achieved the most competitive performance and demonstrated superiority over a single-head deep learning architecture and conventional tree-based machine-learning methods, with 97% test accuracy, 96% F1 score and 0.19 root mean square error. From 447 features, 2 sets of 100 predictors of disease progression were extracted. Feature importance ranking, correlation analysis and descriptive statistics further enriched cluster analysis and validation of the heterogeneity of risk factors.

Costs of Care in Relation to Alzheimer's Disease Severity in Sweden: A National Registry-Based Cohort Study.

The advancement of diagnostic and therapeutic interventions in early Alzheimer's disease (AD) has demanded the economic evaluation of such interventions. Resource utilization and cost estimates in early AD and, more specifically, the amyloid-positive population are still lacking. We aimed to provide cost estimates in AD in relation to disease severity and compare these with the control population. We also aimed to provide cost estimates for a subset of the AD population with both clinical diagnosis and amyloid-positive confirmation. This was a retrospective longitudinal analysis of resource utilization using data from national registries. A cohort from the national Swedish registry for cognitive/dementia disorders (SveDem) includes all clinically diagnosed AD between 2013 and 2020. The study population included 31,951 people with AD and 63,902 age- and sex-matched controls (1:2). The population was followed until death, the end of December 2020, or 2years from the last clinic visit. Direct medical and social costs were estimated from other national registries. Direct medical costs include costs for medications and inpatient and outpatient clinical visits. Direct social costs include costs for institutionalization, home care, short-term care, support for daytime activities, and housing support. Mean annual costs and 95% confidence intervals were obtained by bootstrapping, presented in 2021 Swedish Krona (SEK) (1 SEK=0.117 USD, 1 SEK=0.0985 EUR in 2021), and disaggregated by AD severity, cost component, sex, age group, and care setting. Mean annual costs for individuals with clinically diagnosed AD were SEK 99,906, SEK 290,972, SEK 479,524, and SEK 795,617 in mild cognitive impairment (MCI), mild, moderate, and severe AD. The mean annual costs for the population with both clinical diagnosis and amyloid-positive AD confirmation (N=5610) were SEK 57,625, SEK 179,153, SEK 333,095, and SEK 668,073 in MCI, mild, moderate, and severe AD, respectively. The mean annual costs were higher in institutionalized than non-institutionalized patients, females than males, and older than younger age groups. Inpatient and drug costs were similar in all AD severity stages, but outpatient costs decreased with AD severity. Costs for institutionalization, home care, support for daytime activities, and short-term care increased with AD severity, whereas the cost of housing support decreased with AD severity. This is the first study estimating annual costs in people with AD from MCI to severe AD, including those for the amyloid-positive population. The study provides cost estimates by AD severity, cost components, care settings, sex, and age groups, allowing health economic modelers to apply the costs based on different model structures and populations.

Exploring heterogeneity of treatment effect in patients with sepsis: Protocol for a scoping review.

The average treatment effect (ATE) reported by most randomised clinical trials provides estimates of treatment effects for the theoretical, non-existent average patient. However, ATE may not accurately reflect the outcomes for all subsets of the trial population; some individuals may benefit from the intervention, while others experience worse outcomes or no effect at all. Heterogeneity of treatment effect (HTE) is the non-random and explainable variation in the magnitude or direction of a treatment effect among individuals within a population. Predictive approaches to HTE seek to provide estimates of which treatment of choice is better suited for the individual patient, using regression and/or machine learning techniques. This scoping review aims to investigate the extent to which such predictive approaches to HTE are applied to data from trials on sepsis or septic shock as well as the results of these analyses. The planned review will be conducted in accordance with the PRISMA extension for scoping reviews. We will search Medline, EMBASE, Central, Cinahl and Google Scholar for studies on sepsis or septic shock in which HTE was analysed using predictive approaches. We plan to chart data regarding trial characteristics, patient demographics, disease severity, interventions, outcomes of interest and ATEs, type of predictive approach for the HTE analysis, results from HTE analysis and whether HTE analysis would change an ATE-based trial conclusion. Studies included in the scoping review will be presented as narrative summaries, supplemented with descriptive statistics of quantitative data. The planned scoping review will systematically investigate, summarise and delineate the existing evidence of analysis of HTE in trials on sepsis or septic shock patients as well as their findings, when performed using predictive approaches.

Myocardial SGLT2 expression and cardiac remodeling in patients with severe aortic stenosis: the BIO-AS Study

Abstract Background Cardiac remodeling plays a major role in the prognosis of patients with aortic stenosis (AS) and could impact the benefits of aortic valve replacement. Blood and tissue biomarkers have a differential pattern and expression level in patients with AS, which may retain a pathophysiological role in cardiac remodeling and metabolism. However, the data available are limited and contradictory. Aim Our study aimed to evaluate the expression of sodium-glucose cotransporter 2 (SGLT2) gene and protein in patients with severe AS stratified in high gradient (HG) and low flow-low gradient (LF-LG) AS and its association with cardiac functional impairments. Methods Gene expression and protein levels of main biomarkers of cardiac fibrosis (Galectin-3, sST2, Serpin-4, PINP, PICP, Collagen, TGF-b), inflammation (GDF-15, IL-6, NF-kB), oxidative stress (SOD1, SOD2), and cardiac metabolism (NHE, PPAR-a, PPAR-g, GLUT1, and GLUT4) were evaluated in blood samples and heart biopsies of 45 patients with AS. Results Our study showed SGLT2 gene and protein hyper-expression in patients with LF-LG AS, compared to controls and HG AS (p<0.05). These differences remained significant even after adjusting for age, gender, body mass index, history of diabetes mellitus, arterial hypertension, and coronary artery disease. SGLT2 gene expression was positively correlated with: i) TGF-b (r=0.72, p<0.001) and collagen (r=0.73, p<0.001) as markers of fibrosis; ii) NF-kB (r=0.36, p<0.01) and myocardial IL-6 (r=0.68, p<0.001) as markers of inflammation: iii) SOD2 (r=-0.38, p<0.006) as a marker of oxidative stress; iv) GLUT4 (r= 0.33, p<0.02) and PPAR-a (r=0.36, p<0.01) as markers of cardiac metabolism (Figure 1). Conclusion In patients with LF-LG AS, SGLT2 gene and protein were hyper-expressed in cardiomyocytes and associated with myocardial fibrosis, inflammation, and oxidative stress. The hyper-expression of the SGLT2 gene and protein in patients with LF-LG might pave the way for using SGLT2-Is in this subset population, with the potential to improve the outcomes of AVR and reduce the likelihood of re-hospitalization within one year.Figure 1

Ablation outcome in elderly women with atrial fibrillation undergoing pulsed-field ablation for electrical isolation of pulmonary veins and left atrial posterior wall

Abstract Background Documented evidences indicate higher prevalence of non-paroxysmal atrial fibrillation (AF) as well as in elderly women but also demonstrate the need to go beyond the pulmonary veins (PV) when treating these patients. Objective We compared the ablation outcome in elderly women (>70 years) with that in men in the same age group as well as in younger women (≤70 years) undergoing pulsed-field ablation (PFA) for persistent AF (PerAF). Methods This multicenter study included consecutive PerAF patients undergoing PFA as their first procedure. Patients were divided into 3 groups: Group 1: women >70 years, Group 2: men ≥70 years and Group 3: women ≤70 years. All received PV isolation (PVI) and isolation of left atrial posterior wall (LAPWI). Concentric overlapping lesions were placed in the LAPW. Number of applications were determined on a case-by-case basis. Isolation was confirmed by electrograms recorded on the multispline catheter. In all patients, ICE and fluoroscopy were used to optimize contact between the PFA catheter and the targeted tissue. Arrhythmia-monitoring was performed for 1-year with periodic clinic visits, event recorders and 7-day Holter monitoring. Results A total of 229 patients (group 1: 73; group 2: 47 and group 3: 109) were included in this analysis. Baseline characteristics of the study population is presented in table 1. At 1-year follow-up, 15 (20.5%), 3 (6.38%) and 10 (9.17%) from group 1, 2 and 3 respectively, experienced arrhythmia recurrence off-antiarrhythmic drugs. Recurrence rate in group 1 was significantly higher than that in group 2 (p=0.034) and group 3 (p=0.029). Conclusion In women aged ≤70 years and in elderly men (>70 years), PVI plus isolation of LAPW using ICE-guided PFA was associated with significantly lower recurrence rate compared to that in the elderly women. Given the higher recurrence rate following PVI+LAPWI in the elderly females, the operators should consider addressing all other AF-initiating extra-PV triggers for better ablation-outcome in this subset of the AF population.

Ranolazine therapy is associated with a reduced new diagnosis of diabetes mellitus in chronic coronary syndrome patients: the results of a real-world analysis of an Italian population

Abstract Background Ranolazine (Ran) is an anti-anginal drug acting as a late sodium current inhibitor at a cell membrane level. Some experimental and clinical studies showed an antihyperglycemic effect of the drug, possibly mediated by the increase of insulin secretion, the inhibition of glucagon release, and the protective action on beta-cell function. These effects, additive to the anti-anginal properties of Ran in patients with chronic coronary syndrome (CCS), could modulate and improve glucose metabolic balance. Indeed, data exploring at a population level the association of the drug with diabetes mellitus (DM) incidence are effectively lacking. Aims Aim of this study was to evaluate in CCS patients if the use of Ran, compared with other treatments (No-Ran), was associated with a lower incidence of DM in an Italian real-world clinical setting. Methods Patients included in the database of the National Health System were evaluated (N=6.1 million; about 10% of the Italian population); the recorded information concerned hospitalizations with the related diseases, clinical events, outpatient visits and drug therapy. Patients hospitalized for any cause and discharged with a diagnosis of angina between 2011 and 2020 (ICD-9-CM codes: 413-414) were included in the study after having proved the absence of DM in their medical history. Study population was divided into the Ran (at least one drug prescription) and in the No-Ran cohorts. The mean follow up was 4.3 years for the Ran and 5.0 years for the No-Ran cohorts, respectively. Results The study population included N=171,015 patients (mean age: 72 years, men: 66%). Among them, N=148,808 (No-Ran cohort) were treated with other therapies while N=22,207 (Ran cohort) received Ran. After propensity score matching, Ran (N=6,384) and No-Ran (N=25,536) cohorts did not differ for age, Charlson comorbidity index, use of aspirin and other antithrombotic agents, statins, beta-blockers, Ca-antagonists and nitrates. The incidence of a new diagnosis of DM during the follow-up period was 10.5 and 15.8% in the Ran and in the No-Ran cohorts, respectively (p<0.001). The Cox-regression analysis showed that Ran therapy was associated with a 30% risk reduction to present a new diagnosis of DM (HR=0.70, 95%CI: 0.64-0.76, p<0.001), independently of age, Charlson comorbidity index, heart failure, previous stroke, use of ivabradine, Ca-antagonists and nitrates. Conclusions This real-world study, performed in a whole subset of the Italian population, showed that, in the long-term, the incidence of a new DM diagnosis was lower in Ran users. This association could contribute to explain the benefits of the drug in patients with CCS.

Diagnostic performance of digital tomosynthesis for postoperative assessment of acetabular fractures and pelvic ring injuries.

Digital tomosynthesis (DTS) has broad non-orthopaedic applications and has seen limited use within orthopaedics for imaging of the wrist. The utility of DTS for assessing reduction and hardware placement following operative treatment of pelvic ring injuries and acetabular fractures has not previously been investigated. All operatively treated acetabular fractures and pelvic ring injuries that underwent surgical fixation within a one-year time span received both a computed tomography (CT) scan and a DTS scan as part of their routine postoperative imaging workup. Three orthopaedic traumatologists independently reviewed the images for face-value clinical utility. Radimetrics and PCXMC software were utilized on a subset of the study population's DTS and CT studies to calculate the effective and organ radiation doses delivered. 52 patients (22 acetabular fractures, 22 pelvic ring injuries, 7 pelvic ring and acetabular fractures, 2 femoral head & acetabular fractures) were included. DTS was considered adequate to assess reduction 83% of the time, hardware position 83% of the time, and sufficient to replace the CT scan 67% of the time. DTS was associated with an 8.3 times lower effective radiation dose than CT. All organ doses were lower for DTS than CT. DTS appears to have face-value clinical utility for assessing reduction and hardware position following surgical treatment of acetabular fractures and pelvic ring injuries. Given that DTS is associated with significantly lower radiation doses to patients, further study utilizing more objective criteria is warranted.

Minimally Invasive Transforaminal Versus Lateral Lumbar Interbody Fusion for Degenerative Spinal Pathology: Clinical Outcome Comparison in Patients With Predominant Back Pain.

Retrospective review. To compare perioperative and postoperative clinical outcomes between minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) and lateral lumbar interbody fusion (LLIF) in patients presenting with predominant back pain. Two popular techniques utilized for lumbar arthrodesis are MIS-TLIF and LLIF. Both techniques have reported high fusion rates and suitable postoperative clinical outcomes. Scarce literature exists, however, comparing these 2 common fusion techniques in a subset population of patients presenting with predominant back pain preoperatively. A retrospective review of lumbar procedures performed between November 2005 and December 2021 was conducted using a prospectively maintained single-surgeon database. Inclusion criteria were set as primary, elective, single, or multilevel MIS-TLIF or LLIF procedures for degenerative spinal pathology in patients with predominant preoperative back pain [visual analog scale (VAS) back pain preoperative score > VAS leg preoperative score]. Patients undergoing a revision procedure, single-level procedure at L5-S1, or surgery indicated for infectious, malignant, or traumatic etiologies were excluded. In addition, patients with VAS leg preoperative scores ≥ to VAS back preoperative scores were excluded. Patient demographics, perioperative characteristics, postoperative complications, and patient-reported outcome measures (PROMs) were collected. PROMs included VAS for back and leg pain, Oswestry Disability Index (ODI), and Short Form-12 (SF-12) Item Survey Mental (MCS) and Physical (PCS) Composite Scores with all values collected at the preoperative, 6-week, 12-week, 6-month, 1-year, and 2-year follow-up time point. Patients were grouped into 2 cohorts, depending on whether a patient underwent a MIS-TLIF or LLIF. Demographic and perioperative characteristics were compared between groups using χ2 and Student t test for categorical and continuous variables, respectively. Mean PROM scores were compared between cohorts at each time point utilizing an unpaired Student t test. Postoperative improvement from preoperative baseline within each cohort was assessed with paired samples t test. Achievement of minimum clinical important difference (MCID) was determined by comparing ΔPROM scores to previously established threshold values. MCID achievement rates were compared between groups with χ2 analysis. Statistical significance was noted as a P value <0.05. Eligible study cohort included 153 patients, split into 106 patients in the MIS-TLIF cohort and 47 patients in the LLIF cohort. The mean age was 55.9 years, the majority (57.5%) of patients were males, the mean body mass index was 30.8kg/m2, and the majority of the included cohort were nondiabetic and nonhypertensive. No significant demographic differences were noted between cohorts. The MIS-TLIF cohort had a significantly greater proportion of patients with preoperative spinal pathology of recurrent herniated nucleus pulposus, whereas a significantly greater proportion of patients in the LLIF cohort demonstrated isthmic spondylolisthesis (P < 0.046, all). No significant differences were noted between cohorts for operative duration, estimated blood loss, 1-year rate of arthrodesis, postoperative length of stay, postoperative VAS pain scores on postoperative day 0 or 1, and postoperative narcotic consumption on postoperative day 0 or 1. Patients in the LLIF cohort showed greater rates of postoperative ileus (4.3% vs 0.0%). No other significant differences were noted between cohorts for postoperative complications. Between cohorts, preoperative PROM scores did not significantly differ. The following significant postoperative mean PROM scores were demonstrated: VAS back at 12 weeks and ODI at 12 weeks with both mean scores favoring the LLIF cohort. The MIS-TLIF cohort reported significant improvement from preoperative baseline to the 2-year time point for all PROMs collected at all individual postoperative time points except SF-12 MCS at 6 weeks (P < 0.0, all). LLIF cohort reported significant improvement from preoperative baseline to the 1-year time point for all PROMs collected at all individual postoperative time points except for ODI at 6 weeks, 1 year, and 2 years, SF-12 MCS at 6 weeks and 2 years, and SF-12 PCS at 2 years(P < 0.042, all). The majority of patients in both cohorts achieved overall MCID for VAS back, VAS leg, ODI, and SF-12 PCS. A significantly greater proportion of patients in the LLIF cohort achieved MCID for SF-12 PCS at 12 weeks (94.4% vs 61.1%; P < 0.008). Patients with predominant back pain undergoing MIS-TLIF or LLIF for degenerative spinal pathology demonstrated similar 2-year mean clinical outcomes for physical function, disability, leg pain, and back pain. At the 12-week time point, mean outcome scores for back pain and disability favored the lateral approach with concurrent higher rates of MCID achievement for physical function at that time point.

Anesthesia for Posterior Tracheopexy in Pediatric Patients.

Tracheobronchomalacia refers to an abnormally excessive collapse of the trachea and/or bronchi during exhalation. In the pediatric population, tracheobronchomalacia is increasingly recognized as a cause of morbidity and mortality. Historically, options for medical management and surgical intervention were limited, and patient outcomes were poor. Over the last decade, select US pediatric institutions have devoted significant resources to the establishment of dedicated surgery and anesthesia teams and the development of novel techniques for the successful identification, assessment, and surgical correction of tracheobronchomalacia in a highly complex subset of the pediatric population. The close communication, collaboration, and evolution of anesthesia techniques to meet the unique requirements of new surgical procedures have greatly improved patient safety and optimized outcomes. More than 800 cases have been performed across 2 US pediatric institutions using these techniques. This article reviews the posterior tracheopexy procedure, a newer but increasingly common surgery designed to address tracheobronchomalacia, and provides an overview of related anesthesia considerations and unique challenges. In addition, this article describes novel anesthesia techniques developed specifically to facilitate optimal diagnosis of tracheobronchomalacia and intraoperative management of posterior tracheopexy and similar airway surgeries. These include methods to safely enable 3-phase rigid dynamic bronchoscopy for accurate tracheobronchomalacia diagnosis, recurrent laryngeal nerve monitoring during cervical and thoracic surgical dissection, continuous intraoperative bronchoscopy to enable real-time images during airway reconstruction, and intraoperative assessment of airway repair adequacy to ensure successful correction of tracheobronchomalacia.

Re-examining consumer engagement in the circular economy

PurposeThis study aims to deepen knowledge of consumers’ attitudes towards circular economy products by focusing on the enabling factors that influence their behaviours. The success of the closed-loop economy depends not only on innovation but also on the active participation of the consumer. In these models, the authors witness the transition from the centrality of production to the centrality of use. This paper investigates Italian consumers’ tendency to purchase second-hand products in the clothing sector, one of the most polluting industrial sectors, focusing on the enabling factors that influence their behaviours, the reasons for their purchases and the existence of differences between market segments.Design/methodology/approachTo accomplish this aim, a two-step investigation was carried out: a literature review and a quantitative analysis through a snowball survey involving 963 individuals, noting that non-random sampling restricts the validity of the findings within the considered sub-set of the Italian population. Statistical analyses were performed using the R 4.1.2 software environment along with Rstudio IDE v.1.4.1106 and the packages FactoMineR for cluster analysis and vcd for mosaic plots.FindingsEnvironmental knowledge/awareness and solidarity values have a significant positive effect on consumers’ attitudes and purchasing behaviour towards circular products within the selected sample. A strong statistically significant association (p-value ≪ 0.01) is confirmed between those who consciously purchase sustainable clothing and those who are members/supporters of environmental associations, know sustainable brands and the advantages of the circular economy. Significant relations also emerged in reference to gender and age. In detail, the purchasing of sustainable clothing was found to be positively associated with females and generation Y respondents. Theoretical, institutional and managerial implications stem from the experimental findings of this study.Originality/valueThis study investigates the point of view of demand. From this perspective, this paper proposes a consumer engagement paradigm that highlights the motivations and enabling factors prompting participation in circular economy processes and affecting purchasing practices and attitudes towards second-hand clothing products with regard to Italian consumers.

Https://publishing.emanresearch.org/Journal/Abstract/angiotherapy-81010000

Background: The global prevalence of type 2 diabetes mellitus (T2DM) is projected to rise significantly, with an estimated increase from 536.6 million cases in 2021 to 783.2 million by 2045. Genetic predisposition plays a crucial role in T2DM susceptibility, with the FTO gene, particularly the single nucleotide polymorphism (SNP) rs11076023, being linked to the disease. Methods: A comprehensive literature search was conducted using PubMed, Scopus, and Google Scholar to identify relevant studies that examined the association between the FTO gene rs11076023 polymorphism and T2DM. Case-control studies published until December 31, 2023, were included, adhering to PRISMA guidelines. Data extraction was performed systematically, and statistical analysis was conducted using MetaGenyo to assess the association across various genetic models. Results: The meta-analysis encompassed three studies involving 3,887 participants (1,985 cases and 1,902 controls). The findings demonstrated a significant association between the T allele of rs11076023 and increased T2DM risk, particularly within the recessive genetic model (TT vs. TA + AA), indicating a higher susceptibility among individuals with the TT genotype. In contrast, the over-dominant model suggested a protective effect associated with the TA heterozygous genotype. Notable heterogeneity was observed across the studies, and sensitivity analyses confirmed the robustness of the associations. Conclusion: This meta-analysis highlights the FTO gene rs11076023 polymorphism as a significant genetic factor influencing T2DM susceptibility, particularly within certain population subsets. The findings underscore the complexity of T2DM risk, emphasizing the interplay between genetic factors and lifestyle choices. Further research with larger, diverse populations is necessary to validate these associations and explore the underlying biological mechanisms, which may inform targeted interventions for T2DM prevention and management.

Accuracy of Mandibular Foramen Localization Using Digital Orthopantomogram (OPG) in Middle Eastern Population.

Locating the mandibular foramen (MF) through imaging is clinically important for inferior alveolar nerve (IAN) anesthesia and mandibular ramus osteotomies. Although cone-beam computed tomography (CBCT) is superior in imaging the mandible, an orthopantomogram (OPG) is preferred for its ease of use and availability. Therefore, the present study aimed to evaluate the accuracy of digital OPG in localizing the MF, in a subset of the Middle Eastern population. Radiographic images (OPG and CBCT) of selected patients (adults, dentulous and no mandibular abnormalities) were used to locate the MF through digital measurements (mm) of the anteroposterior distance from the anterior border of the ramus (MF-AP) and the superoinferior position from the mandibular occlusal plane (MF-SI). Measurements were statistically compared between OPG and CBCT for accuracy. Differences in measurements between OPG and CBCT were compared against the anatomic location (right/left), age and biological sex, assuming a p-value < 0.05 as significant. A total of 204 radiographic records (males: 100/females: 104/mean age: 34.65 ± 11.55 years) were evaluated. The measurements for the MF were MF-AP-OPG (right: 13.53 ± 2.44/left: 13.19 ± 2.25), MF-AP-CBCT (right: 13.61 ± 2.39/left: 13.36 ± 2.19), MF-SI-OPG (right: 5.25 ± 1.71/left: 5.41 ± 1.65) and MF-SI-CBCT (right: 5.59 ± 1.66/left: 5.52 ± 1.61). Measurements between OPG and CBCT were not significantly different, except for MF-SI (right) (p = 0.042). While the overall difference between OPG and CBCT (MF-AP/MF-SI) measurements showed a significant association (p < 0.01) with the anatomic location (right/left), a significant association (p < 0.05) with biological sex was observed only for MF-AP. Based on this study's outcomes, digital OPG is an accurate modality to locate the MF based on anteroposterior (MF-AP) and superoinferior (MF-SI) measurements. This would be clinically beneficial for dental and oral surgeons to achieve the optimum IAN block anesthesia based on preoperative panoramic radiographs. Similarly, it would assist maxillofacial surgeons in planning mandibular orthognathic surgeries and ramus osteotomies without complications.

Chlamydia muridarum Causes Persistent Subclinical Infection and Elicits Innate and Adaptive Immune Responses in C57BL/6J, BALB/cJ and J:ARC(S) Mice Following Exposure to Shedding Mice.

Chlamydia muridarum (Cm) has reemerged as a moderately prevalent infectious agent in research mouse colonies. Despite its' experimental use, few studies evaluate Cm's effects on immunocompetent mice following its natural route of infection. A Cm field isolate was administered (orogastric gavage) to 8-week-old female BALB/cJ (C) mice. After confirming shedding (through 95d), these mice were cohoused with naïve C57BL/6J (B6), C, and Swiss (J:ARC[S]) mice (n=28/strain) for 30 days. Cohoused mice (n=3-6 exposed and 1-6 control/strain) were evaluated 7, 14, 21, 63, 120, and 180 days post-cohousing (DPC) via hemograms, serum biochemistry analysis, fecal qPCR, histopathology, and Cm MOMP immunohistochemistry. Immunophenotyping was performed on spleen (B6, C, S; n=6/strain) and intestines (B6; n=6) at 14 and 63 DPC. Serum cytokine concentrations were measured (B6; n=6 exposed and 2 control) at 14 and 63 DPC. All B6 mice were shedding Cm by 3 through 180 DPI. One of 3 C and 1 of 6 S mice began shedding Cm at 3 and 14 DPC, respectively, with the remaining shedding thereafter. Clinical pathology was nonremarkable. Minimal-to-moderate enterotyphlocolitis and gastrointestinal associated lymphoid tissue (GALT) hyperplasia was observed in 15 and 47 of 76 Cm-infected mice, respectively. Cm antigen was frequently detected in GALT-associated surface intestinal epithelial cells. Splenic immunophenotyping revealed increased monocytes and shifts in T cell population subsets in all strains/timepoints. Gastrointestinal immunophenotyping (B6) revealed sustained increases in total inflammatory cells and elevated cytokine production in innate lymphoid cells and effector T cells (large intestine). Elevated concentrations of pro-inflammatory cytokines were detected in the serum (B6). Results demonstrate that while clinical disease was not appreciated, 3 commonly utilized strains of mice are susceptible to chronic enteric Cm infection which may alter various immune responses. Considering the widespread use of mice to model GI disease, institutions should consider excluding Cm from their colonies.

Willingness to pay for a tobacco-free life: a contingent valuation assessment.

Tobacco, being an established risk factor for significant mortality and morbidity, causes over 7 million annual deaths globally. India is a country with over 270 million active tobacco users. On the one hand, although the willingness to quit amongst tobacco users is as high as 55.4%, the actual quit rates translate to less than 20%. Taking a cue from the economic principle of commitment and consistency, paying a nominal fee can serve as a form of public commitment and motivation to decrease the dropout rate amongst those committed to quitting. This study uses contingent valuation assessment to determine the willingness to pay (WTP) values for an effective tobacco cessation service across individuals with different socio-demographic characteristics. A cross-sectional observational study with multistage cluster sampling in Rajasthan was conducted to recruit 360 active tobacco users from 8 districts. Q-Q plots were used to determine the non-parametric distribution, and statistical differences between median WTP values were compared using Mann-Whitney U and Kruskal-Wallis H tests, considering a p-value less than 0.05 to be statistically significant. The majority of participants were males (57.78%) between the ages of 26 and 35 (40.28%), married (82.50%), and with children (65.83%), with an annual income between USD 7500-10,000 (23.61%) and graduate-level education (40.56%). Exclusive smokers formed the majority of the cohort (48.06%), and 50.83% were willing to quit as well as willing to pay for cessation. Median WTP values were maximum for males (USD 54.05; p<0.05), age group 26-35 years (USD 54.05; p<0.05), post-graduates (USD 81.08; p<0.05), and annual income above USD 20,000 (USD 121.62; p<0.05). Weak positive and significant correlations were observed between WTP and annual spending on tobacco, annual spending on health, and annual income. The study emphasizes the critical importance of early-age interventions for effective tobacco cessation prior to transitioning into dependency, resulting in reduced financial parity for availing health services. These are the first such WTP values from the Southeast Asian region, tailored for different population subsets, specifically for tobacco cessation. Our findings contribute to the growing body of evidence to support innovative approaches to enhance tobacco cessation efforts through financial commitments.