Large Increase Research Articles

Self-poisoning in young Australians: The impact of COVID-19 and recent trends following easing of restrictions

Introduction: Self-poisoning is the most common form of hospitalised self-harm in young people and has been increasing over the last decade. The COVID-19 pandemic was associated with further increases in self-harm in adolescents. There are limited data on changes after pandemic restrictions ended. This study aimed to describe recent trends in self-poisoning in young people. Setting: Australia 2018–2023. Methods: A retrospective analysis of self-poisoning calls to Australia’s poisons information centres. Intentional poisoning exposures in people aged 5–19 years were included in the main analysis. We also examined intentional poisonings in people aged 20 and over for comparison. We used interrupted time-series analysis to estimate the impact of COVID-19 (March 2020) and ‘re-opening’ (December 2021), when many restrictions were lifted in Australia. We compared effects in the jurisdictions with most disruptions and lockdowns with other jurisdictions. Results: There were 201,755 self-poisonings documented, 64% female, with 19,946 children (aged 5–14, 9.9%) and 44,388 adolescents (aged 15–19, 22.0%). There was a steep increase in the rate of poisoning in female children and adolescents – with the annual increase being 1.361 (95% confidence interval = [1.074, 1.735]) and 1.154 (95% confidence interval = [1.049, 1.283]) times faster than pre-pandemic trends in these two groups between March 2020 and December 2021. Following relaxation of restrictions, there was a sudden drop and then slow decline in self-poisonings (despite rising COVID-19 infection rates). There was an overall 29.6% increase in intentional poisonings in young people over the study period. This is markedly more pronounced among young females (37.0%) vs males (11.2%). There were substantial jurisdictional variations, with larger increases in Victoria, Tasmania and the Australian Capital Territory. Conclusion: There has been a marked increase in child and adolescent female self-poisonings over the last 6 years, with increases strongly associated with COVID-19 pandemic restrictions but persisting after their removal.

Abstract 4118762: Large-scale multinational trends in the use of cardioprotective antihyperglycemic agents as first-line therapy in patients with type 2 diabetes and cardiovascular disease: a LEGEND-T2DM study

Background: US guidelines for type 2 diabetes (T2DM) recommend metformin as first-line anti-hyperglycemic therapy (AHT), but prioritizing the use of AHTs that reduce cardiovascular disease (CVD) risk – GLP1-RAs and SGLT2is – is increasingly suggested for people with CVD. We examine the multinational use patterns of GLP1-RAs, SGLT2is, DPP4is, and sulfonylureas (SUs) as first-line therapies for patients with CVD. Methods: In 10 US and 6 non-US databases between 2016 and 2021 mapped to a common data model [A], we measured yearly initiation of GLP1-RAs, SGLT2is, DPP4is, and SUs as first-line AHTs in patients with T2DM with and without CVD [B]. We also compared the initiation of the drug classes as second-line after metformin. We calculated the annual rate of change in proportional initiation of each drug class as first-line AHT and assessed differences in trends as group x time interactions in linear mixed models. Results: Across all data sources, 3.3 million patients with T2DM used GLP1-RAs, SGLT2is, DPP4is, or SUs as first-line AHTs, and 3.9m initiated these drug classes as second-line AHT after metformin. Within the first-line cohort, 1.4m (41%) had established CVD compared with 1.2m (31%) in the second-line cohort. For GLP1-RAs and SGLT2is, the annual rate of their relative use as first-line agents increased among patients with T2DM with CVD (GLP1RAs: ranging 1.3-5.4% in US [C] and 0.3-0.8% in non-US [D], SGLT2is: 2.1-12.9% in US [E] and 8.1-10.6% in non-US databases [F]). There was a larger relative increase in the use of SGLT2i and a smaller increase in GLP1RA use in CVD vs non-CVD cohorts (P interaction <.001). While there was a larger increase in GLP1RAs uptake in the US cohorts, SGLT2i use increased more in non-US cohorts ([C-F], P interaction <.001 for all, except .01 for SGLT2i). Of note, across cohorts, the uptake of GLP1RA and SGLT2i as first-line was higher than second-line use among those with CVD (P interaction <.001). In contrast, DPP4i and SU use as first-line was lower than GLP1RA and SGLT2is and decreased over time (P<.001). Conclusions: In a large-scale multinational, federated cohort of patients with T2DM, the use of cardioprotective agents increased as first-line AHT, with variation in SGLT2i and GLP1RAs uptake across study cohorts.

More extremely hot days, more heat exposure and fewer cooling options for people of color in Connecticut, U.S.

It is well-documented that people of color in the U.S. are disproportionately exposed to extreme urban heat. However, most studies have focused on large cities for one point in time, and less is known about how heat exposure changes over time in smaller cities. Here, we present a study of the changing nature of urban heat exposure and cooling strategies for ten cities in Connecticut in the U.S. Our results show that people of color experience more heat exposure and fewer adaptation strategies. They experienced higher overall temperatures, more extremely hot days, and larger increases in heat exposure. Also, they have lower air conditioning ownership rates and lower tree cover. Taken together, the results indicate that people of color are not only exposed to higher temperatures but also disproportionately exposed to increasing temperatures over time. With lower heat adaptation capacity, people of color are more vulnerable to increasing urban heat.

Improved clinical and radiographic outcomes with expandable cages in transforaminal lumbar interbody fusion: a propensity-matched cohort analysis.

The restoration of sufficient overall lumbar lordosis (LL) and segmental LL (SL) is associated with achieving optimal sagittal balance, decreasing back pain, and enhancing functional outcomes for patients. Expandable cages were developed in hopes of improving radiographic parameters and clinical outcomes, although current clinical evidence is inconclusive. Here, the authors aimed to evaluate the clinical and radiographic outcomes in patients undergoing one- or two-level open transforaminal lumbar interbody fusion (TLIF) with expandable versus static cage placement, using propensity-matched cohorts. An institutional retrospective cohort of patients who underwent one- or two-level open TLIF with either expandable cage or static cage placement was identified. Using relevant preoperative covariates, including age, primary versus revision operation, number of cages implanted, and surgical level implanted, the authors built propensity-matched cohorts. They identified clinical outcomes in both cohorts, including operative characteristics and complication rates, along with pain, weakness, and sensory deficits over follow-up. Furthermore, they extracted and examined preoperative, postoperative, and last follow-up radiographic parameters. A total of 148 patients were included, and they were followed for a mean of 1.7 years (range 0.5-4.3 years). Propensity matching was used to create cohorts of patients who were similar with respect to age, surgical indication, revision status, number of cages implanted, surgical level implanted, and length of follow-up. Patients in both groups had similar preoperative radiographic parameters. Patients with expandable cages saw larger increases in SL, both postoperatively (5.3° ± 7.5° vs 1.6° ± 5.6°, p = 0.006) and at last follow-up (5.7° ± 7.4° vs 1.0° ± 6.1°, p = 0.003). They also saw significant improvements in pelvic incidence minus LL mismatch at last follow-up (-4.4° ± 13.2° vs 5.8° ± 13.8°, p = 0.009). No differences in intraoperative or perioperative complications were found, but patients with expandable cages were less likely to require readmission, develop adjacent-segment disease, or require revision surgery. They were also more likely to be symptom free at 1 month after surgery and at last follow-up. Expandable cages lead to better restoration of radiographic features, including SL and improvements in clinical outcomes, compared with static cages in propensity-matched cohorts in patients undergoing one- or two-level open TLIFs.

The dynamic range of immunoassays for heparin-induced thrombocytopenia

BackgroundFollowing the current guidelines, immunoassays for the diagnosis of heparin-induced thrombocytopenia (HIT) are interpreted dichotomously, with test results categorized as either positive or negative. However, the extent to which test results hold diagnostic significance across the entire dynamic range remains unclear. ObjectivesWe utilized data from the prospective TORADI-HIT study, comprising 1,393 consecutive patients with suspected HIT, to assess the diagnostic significance of two H/PF4 immunoassay test results across their respective dynamic ranges: HemoSil Acustar HIT IgG [CLIA] and Lifecodes PF4 IgG [ELISA]. MethodsHIT diagnosis was determined by a washed-platelet heparin-induced platelet activation assay (HIPA). For each measurement point in the dataset, we computed likelihood ratios (LR), sensitivities, and specificities. To provide post-test probabilities for individual test results, we calculated interval-specific likelihood ratios and integrated it into a web-based calculator. ResultsThe prevalence of HIT was 8.5% (n = 119). A likelihood ratio of ≥ 10 was first achieved at 0.3% of the dynamic range (0.4 U/ml; CLIA) and 16% (0.64 OD; ELISA), respectively. A likelihood ratio of ≥ 100 was present at 9.4% (12 U/ml; CLIA) and 75.0% (3.0 OD; ELISA). The slope of the linear regression line (LR ∼ dynamic range) was 9.5 (CLIA) and 0.9 (ELISA). ConclusionDespite both immunoassays showing an association between results and diagnostic significance, the strength of that association varies by assay. CLIA has a larger increase per measurement unit. Post-test probabilities for individual patients can be estimated using a web-based calculator: https://pcd-research.shinyapps.io/BayesianCalculator/.

Use, perceptions, and effectiveness of e-cigarettes for smoking cessation among older adults in England: a population study, 2014–2024

BackgroundThis study aimed to characterise patterns of tobacco smoking and vaping among older adults (≥ 65 years) in England, to explore harm perceptions of e-cigarettes among those who smoke, and to estimate the real-world effectiveness of e-cigarettes for helping older adults to stop smoking.MethodsData were collected as part of a representative monthly cross-sectional household survey in England between April 2014 and April 2024 (n = 197,219). We analysed differences between older (≥ 65 years) and younger/middle-aged adults (18–64 years) in (a) time trends in tobacco smoking and vaping, (b) harm perceptions of e-cigarettes vs. cigarettes (adjusting for gender, socioeconomic position, and vaping status), and (c) the real-world effectiveness of e-cigarettes for smoking cessation (adjusting for gender, socioeconomic position, characteristics of the quit attempt, and use of other evidence-based cessation aids).ResultsTobacco smoking prevalence remained relatively unchanged over time among older adults (at ~ 9%; 9.5% [8.5–10.6%] in April 2014 and 8.7% [7.7–9.8%] in April 2024) but vaping prevalence increased (from 2.1% [1.6–2.7%] to 3.7% [3.0–4.6%], respectively). These trends differed from those observed among younger/middle-aged adults, among whom there was a clear decline in smoking (from 21.8% [21.0–22.7%] to 18.2% [17.3–19.0%]) and a larger increase in vaping (from 5.6% [5.2–6.1%] to 16.2% [15.3–17.0%]). Older adults were consistently less likely than younger/middle-aged adults to use e-cigarettes to support attempts to quit smoking (26.8% [17.2–39.3%] vs. 43.7% [39.6–48.0%] in April 2024). Older smokers reported greater uncertainty about the harms of e-cigarettes compared with cigarettes (ORadj = 2.48 [2.28–2.69]). E-cigarettes appeared to be effective for helping older adults to stop smoking (ORadj = 1.50 [0.96–2.34]); whether effectiveness was lower than for younger/middle-aged adults was inconclusive.ConclusionsOver the past decade, smoking prevalence has remained stable among older adults while decreasing among the rest of the adult population in England. Older adults are more unsure about the relative harms of e-cigarettes and less likely to use them to support attempts to quit smoking, despite evidence that they are effective for smoking cessation in this population.

Presence of Atrial Fibrillation (AF) is a poor prognostic marker in patients with Heart Failure with reduced Ejection Fraction (HFrEF) and Left Bundle Branch Block (LBBB)

Abstract Background Observational data indicate that between 20-30% of patients with HFrEF have LBBB. While numerous independent variables are implicated in the overall prognosis of these patients, this group of patients respond poorly to medical therapy. Presence of AF further impairs the functioning of the left ventricle by several mechanisms e.g., left atrial dilatation, decreased left ventricular filling, irregular cycle length, functional mitral regurgitation etc. Literature is sparse on the cumulative effect of AF in this group of patients. Purpose To assess the effect of AF on left ventricular ejection fraction (LVEF) and mortality in patients presenting with HFrEF and LBBB Methods Single centre, retrospective, observational study over 33 months (Jan 2021 – Sept 2023). Patients with HFrEF and LBBB (as defined by the European Society of Cardiology, 2021) identified from the heart failure database. Results (Table) N=80 Whole cohort: age 74.8 +/- 13.6 years (median:79, range 39-96); 57/80 (67.5%) males. Hypertension [41/80 (51.3%)] was most common comorbidity. Majority were on 3 drugs (23/80, 28.8%) of guideline directed medical therapy (GDMT) with ~1 in 4 patients [19/80 (23.8%)] on all 4 drugs. 32/80 (40.0%) were in AF, remainder in sinus rhythm (SR). Mean baseline LVEF: 21.8 +/- 8.4. Mean LVEF continued to be ≤35% (paired echocardiograms available in 50.0% patients) inspite of GDMT. The QRS duration continued to prolong on follow-up. Patients in AF were statistically significantly older, were less often on all 4 GDMT drugs (particularly sodium glucose transporter 2 inhibitors - SGLT2i’s), and were less likely to survive than those in SR. No difference in comorbid conditions or QRS prolongation on follow-up were seen between patients with AF versus SR. There was trend towards a larger increase in mean LVEF in patients with SR than AF. Conclusions In our experience, patients with HFrEF and LBBB continue to have a high mortality (45.0% at ~ 3 years) inspite of GDMT. AF is seen in a high percentage of patients (40.0%) in this cohort, worsening the prognosis further, with mortality nearly 3 times higher than those in SR. Aggressive management of patients with HFrEF and LBBB with, where indicated, early cardiac resynchronisation therapy (CRT) and more so, of those with AF (with +/- atrioventricular node ablation or left atrial ablation) should be considered at an early stage after diagnosis.Table

Exploring Functional Gene XsPDAT1’s Involvement in Xanthoceras sorbifolium Oil Synthesis and Its Acclimation to Cold Stress

Phospholipid: diacylglycerol acyltransferase (PDAT) is crucial in triacylglycerol (TAG) synthesis as it represents the final rate-limiting step of the acyl-CoA-independent acylation reaction. PDAT not only regulates lipid synthesis in plants, but also plays an important function in improving stress tolerance. In this study, the full-length coding sequence (CDS) of XsPDAT1, totaling 2022 base pairs and encoding 673 amino acids, was cloned from Xanthoceras sorbifolium. The relative expression of XsPDAT1 was significantly and positively correlated with oil accumulation during seed kernel development; there were some differences in the expression patterns under different abiotic stresses. Transgenic Arabidopsis thaliana plants overexpressing XsPDAT1 were obtained using the Agrobacterium-mediated method. Under low-temperature stress, the transgenic plants exhibited a smaller decrease in chlorophyll content, a smaller increase in relative conductivity, and a larger increase in POD enzyme activity and proline content in the leaves compared with the wild type. Additionally, lipid composition analysis revealed a significant increase in unsaturated fatty acids, such as oleic (C18:1) and linoleic (C18:2), in the seeds of transgenic plants compared to the wild type. These results suggest that XsPDAT1 plays a dual role in regulating the ratio of fatty acid composition and low-temperature stress in plants.

A higher peak heart rate during head-up tilt test predicts the therapeutic efficacy of metoprolol in vasovagal syncope

BackgroundAlthough beta blockers, such as metoprolol, have been widely used in the management of vasovagal syncope (VVS), their efficacy remains debated, with larger studies showing limited benefit. Identifying patient-specific characteristics that predict a positive response to metoprolol could optimize its use. This study aims to investigate the key factors that may determine which VVS patients are suitable candidates for metoprolol treatment.MethodsThis retrospective study was conducted at a single center. Patients diagnosed with VVS and treated with metoprolol for a minimum of three months were included. A 50% reduction in syncope symptom score (SS) after three months of metoprolol treatment was used to define metoprolol responders, while those who did not achieve this reduction were classified as non-responders. After a three-month follow-up, patients were divided into two groups: responders and non-responders. Baseline data—including age, gender, comorbidities, laboratory tests, and the type of VVS—were analyzed for each patient. Changes in heart rate (HR) and blood pressure during the head-up tilt test (HUTT) were also evaluated between the two groups. Logistic regression analysis was performed to identify potential predictors of metoprolol response, and receiver operating characteristic (ROC) curve analysis was used to assess the value of these predictors in selecting potential responders.ResultsA total of 168 VVS patients were enrolled between January 2016 and December 2020. Of these, 100 patients responded positively to metoprolol, while 68 did not. No significant differences in baseline characteristics or HUTT results were observed between the two groups (p > 0.05). However, responders exhibited a significantly higher peak HR compared to non-responders during the HUTT (120.13 ± 19.33 vs. 106.60 ± 22.32, p < 0.001). The increase in HR was also more pronounced in responders (0.60 ± 0.23 vs. 0.41 ± 0.25, p < 0.001). Additionally, HR variability was significantly greater in responders than in non-responders (16.18 ± 5.51 vs. 12.61 ± 5.50, p < 0.001).ConclusionHigher peak HR, larger increases in HR, and greater HR variability during the HUTT may serve as reliable predictors of a positive response to metoprolol in patients with VVS.

Gastrointestinal permeability and kidney injury risk during hyperthermia in young and older adults.

We tested whether older adults, compared with young adults, exhibit greater gastrointestinal permeability and kidney injury during heat stress. Nine young (32±3 years) and nine older (72±3 years) participants were heated using a model of controlled hyperthermia (increasing core temperature by 2°C via a water-perfused suit). Gastrointestinal permeability was assessed using a multi-sugar drink test containing lactulose, sucrose and rhamnose. Blood and urine samples were assayed for markers of intestinal barrier injury [plasma intestinal fatty acid binding protein (I-FABP), plasma lipopolysaccharide binding protein (LBP) and plasma soluble cluster of differentiation 14 (sCD14)], inflammation (serum cytokines), kidney function (plasma creatinine and cystatin C) and kidney injury [urine arithmetic product of IGFBP7 and TIMP-2 (TIMP-2 × IGFBP7), neutrophil gelatinase-associated lipocalin and kidney injury molecule-1]. The lactulose-to-rhamnose ratio was increased in both young and older adults (group-wide: Δ0.11±0.11), but the excretion of sucrose was increased only in older adults (Δ1.7±1.5). Young and older adults showed similar increases in plasma LBP (group-wide: Δ0.65±0.89µg/mL), but no changes were observed for I-FABP or sCD14. Heat stress caused similar increases in plasma creatinine (group-wide: Δ0.08±0.07mg/dL), cystatin C (group-wide: Δ0.16±0.18mg/L) and urinary IGFBP7×TIMP-2 [group-wide: Δ0.64±0.95 (pg/min)2] in young and older adults. Thus, the level of heat stress used herein caused modest increases in gastrointestinal permeability, resulting in a mild inflammatory response in young and older adults. Furthermore, our data indicate that older adults might be more at risk for increases in gastroduodenal permeability, as evidenced by the larger increases in sucrose excretion in response to heat stress. Finally, our findings show that heat stress impairs kidney function and elevates markers of kidney injury; however, these responses are not modulated by age.

Ethnoracial variation in school victimization and adolescent substance use

Adolescent substance abuse is a pressing public health concern. While a large literature has investigated factors linked to adolescent substance use and its outcomes, less research considers the intersection of race-ethnicity, school victimization, and substance use. The present study uses nationally representative data from the 2009–2019 Youth Risk Behavior Surveillance System (n = 66,906) and insights from stress process and critical race perspectives to examine ethnoracial variation in associations between school victimization (i.e., bullied, threatened with a weapon, and feeling unsafe on the way to school) and use of substances (i.e., hard drugs, tobacco, alcohol, and marijuana). Results showed that all victimization measures were associated with significant increases in using all four substances. Compared with whites, Native Americans experienced higher odds of using most substances while Asians and Blacks were generally less likely to use substances. Race-ethnicity moderated victimization-substance use associations, but patterns diverged based on victimization form and substance under consideration. Threats involving a weapon were linked to greater hard drug use for white and Hispanic adolescents than Blacks. School safety concerns were associated with larger increases in Asian adolescents’ hard drug use than whites, Blacks, and Hispanics, and greater marijuana use for Hispanic and white adolescents relative to Blacks. This study complicates the significance of school victimization for substance use such that race-ethnicity factors to a great extent into the presence of associations.

Effects of Exercise Training on Mitochondrial and Capillary Growth in Human Skeletal Muscle: A Systematic Review and Meta-Regression.

Skeletal muscle mitochondria and capillaries are crucial for aerobic fitness, and suppressed levels are associated with chronic and age-related diseases. Currently, evidence-based exercise training recommendations to enhance these characteristics are limited. It is essential to explore how factors, such as fitness level, age, sex, and disease affect mitochondrial and capillary adaptations to different exercise stimuli. The main aim of this study was to compare the effects of low- or moderate intensity continuous endurance training (ET), high-intensity interval or continuous training (HIT), and sprint interval training (SIT) on changes in skeletal muscle mitochondrial content and capillarization. Secondarily, the effects on maximal oxygen consumption (VO2max), muscle fiber cross-sectional area, and fiber type proportion were investigated. A systematic literature search was conducted in PubMed, Web of Science, and SPORTDiscus databases, with no data restrictions, up to 2 February 2022. Exercise training intervention studies of ET, HIT, and SIT were included if they had baseline and follow-up measures of at least one marker of mitochondrial content or capillarization. In total, data from 5973 participants in 353 and 131 research articles were included for the mitochondrial and capillary quantitative synthesis of this review, respectively. Additionally, measures of VO2max, muscle fiber cross-sectional area, and fiber type proportion were extracted from these studies. After adjusting for relevant covariates, such as training frequency, number of intervention weeks, and initial fitness level, percentage increases in mitochondrial content in response to exercise training increased to a similar extent with ET (23 ± 5%), HIT (27 ± 5%), and SIT (27 ± 7%) (P > 0.138), and were not influenced by age, sex, menopause, disease, or the amount of muscle mass engaged. Higher training frequencies (6 > 4 > 2 sessions/week) were associated with larger increases in mitochondrial content. Per total hour of exercise, SIT was ~ 2.3 times more efficient in increasing mitochondrial content than HIT and ~ 3.9 times more efficient than ET, while HIT was ~ 1.7 times more efficient than ET. Capillaries per fiber increased similarly with ET (15 ± 3%), HIT (13 ± 4%) and SIT (10 ± 11%) (P = 0.556) after adjustments for number of intervention weeks and initial fitness level. Capillaries per mm2 only increased after ET (13 ± 3%) and HIT (7 ± 4%), with increases being larger after ET compared with HIT and SIT (P < 0.05). This difference coincided with increases in fiber cross-sectional area after ET (6.5 ± 3.5%), HIT (8.9 ± 4.9%), and SIT (11.9 ± 15.1%). Gains in capillarization occurred primarily in the early stages of training (< 4weeks) and were only observed in untrained to moderately trained participants. The proportion of type I muscle fibers remained unaltered by exercise training (P > 0.116), but ET and SIT exhibited opposing effects (P = 0.041). VO2max increased similarly with ET, HIT, and SIT, although HIT showed a tendency for greater improvement compared with both ET and SIT (P = 0.082), while SIT displayed the largest increase per hour of exercise. Higher training frequencies (6 > 4 > 2 sessions/week) were associated with larger increases in VO2max. Women displayed greater percentage gains in VO2max compared with men (P = 0.008). Generally, lower initial fitness levels were associated with greater percentage improvements in mitochondrial content, capillarization, and VO2max. SIT was particularly effective in improving mitochondrial content and VO2max in the early stages of training, while ET and HIT showed slower but steady improvements over a greater number of training weeks. The magnitude of change in mitochondrial content, capillarization, and VO2max to exercise training is largely determined by the initial fitness level, with greater changes observed in individuals with lower initial fitness. The ability to adapt to exercise training is maintained throughout life, irrespective of sex and presence of disease. While training load (volume × intensity) is a suitable predictor of changes in mitochondrial content and VO2max, this relationship is less clear for capillary adaptations.

Mathematical modeling suggests heterogeneous replication of Mycobacterium tuberculosis in rabbits.

How quickly Mycobacterium tuberculosis ( Mtb ) replicates and dies in lungs of infected individuals is likely to determine the outcome of the infection - either control/clearance of the bacteria by the host immune response or progression to active disease, tuberculosis ( TB ). And yet, only a few studies, primarily in mice, rigorously estimated the rates of Mtb replication and death during an in vivo infection. We infected rabbits with a novel clinical isolate of Mtb carrying an unstable, "replication clock" plasmid and followed the dynamics of bacteria over time. Interestingly, previous methods developed to estimate Mtb replication and death rates using similar data for Mtb infection of mice failed to describe our novel data on Mtb dynamics in rabbits; we showed that heterogeneous dynamics of Mtb in semi-independent subpopulations in lungs of Mtb-infected rabbits may be one explanation of this failure of the method. Our results highlight potential differences in Mtb dynamics in different mammalian hosts and suggest ways to evaluate heterogeneity of Mtb replication and death rates in vivo.

Employing Titanium Dioxide Nanoparticles as Biostimulant against Salinity: Improving Antioxidative Defense and Reactive Oxygen Species Balancing in Eggplant Seedlings.

Salinity is a major abiotic stress that affects the agricultural sector and poses a significant threat to sustainable crop production. Nanoparticles (NPs) act as biostimulants and significantly mitigate abiotic stress. In this context, this experiment was designed to assess the effects of foliar application of titanium dioxide (TiO2) nanoparticles at 200 and 400 ppm on the growth of eggplant (Solanum melongena) seedlings under moderate (75 mM) and high (150 mM) salinity stress. The TiO2-NPs employed were characterized by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), thermal gravimetric analysis (TGA), and scanning electron microscopy (SEM) analysis. The seedlings were assessed physiologically, growth-wise, and biochemically. The seedlings were significantly affected by their physiological attributes (Fv'/Fm', Fv/Fm, NPQ), growth (root length, shoot length, number of leaves, fresh biomass, dry biomass, leaf greenness), antioxidative enzymes (SOD, POD, CAT, APx, GR), stress indicators (H2O2, MDA), and toxic ion (Na+) concentrations. The maximum decrease in physiological and growth attributes in eggplant seedling leaves was observed with no TiO2-NP application at 150 mM NaCl. Applying TiO2-NPs at 200 ppm showed significantly less decrease in Fv'/Fm', root length, shoot length, number of leaves, fresh biomass, dry biomass, and leaf greenness. In contrast, there were larger increases in SOD, POD, CAT, APx, GR, and TSP. This led to less accumulation of H2O2, MDA, and Na+. No significant difference was observed in higher concentrations of TiO2-NPs compared to the control. Therefore, TiO2-NPs at 200 ppm might be used to grow eggplant seedlings at moderate and high salinity.

5071 Impact of Estrogen Replacement Therapy on Bone Health in a Novel Non-human Primate Model of Postmenopausal Women Living with HIV

Abstract Disclosure: K. Sauter: None. D.L. Takahashi: None. G. Webb: None. H. Hofmeister: None. O. Varlamov: None. J. Sacha: None. P. Kievit: None. Current antiretroviral therapy (ART) regimens have rendered HIV a manageable chronic condition rather than a fatal disease, with people who initiate ART soon after infection achieving nearly normal life expectancy. As a consequence of increased survival, more women living with HIV (WLWH) will now undergo menopause and be subject to a disease burden that reflects age along with adverse skeletal consequences of postmenopausal estrogen deficiency. In addition to known bone loss and increased fracture risk in postmenopausal women, ART also causes decreased bone mineral density. Therefore ART-suppressed WLWH may have a compounded detrimental effect on bone due to long-term ART treatment combined with menopause that may be attenuated with estrogen replacement. Eleven rhesus macaques were infected intravenously with SIVmac239M and received ART two weeks post-infection (PI). All animals were ovariectomized (OVX) at 35 weeks PI and received estrogen implants (n=6) or cholesterol implants (n=5). Weekly blood samples were collected and animals were monitored longitudinally for body composition including bone mineral content (BMC) via dual x-ray absorptiometry (DEXA). Infection with SIV caused a significant decrease, -8.2%, in pelvis BMC after 14 days of peak viremia with SIV. These changes were not observed in the BMC of spine or extremities. BMC remained suppressed by ∼7% for an additional 25 weeks PI during ART treatment. Measurement of circulating bone turnover markers (BTMs), osteocalcin and C-terminal telopeptide of type 1 collagen (CTX), decreased post infection without significant improvement after ART suppression. Induction of menopause via OVX and loss of estrogen induced a drastic increase in BTMs with a much larger increase in CTX, indicating potential global bone loss due to OVX. Post-implant, the control animals’ pelvis BMC continued to decrease to -20.9% and pelvis BMD to -9.3% indicating that OVX further exacerbated the effect of SIV and ART. However, animals that received estrogen implants demonstrated marked improvement in both measures to greater than baseline. SIV and subsequent long-term ART negatively impact pelvic BMC and BMD and this effect is compounded by menopause in our model of post-menopausal WLWH. However, estrogen replacement post-menopause may attenuate these detrimental bone effects despite long-term ART treatment. Presentation: 6/1/2024

Graphene Bilayer as a Template for Manufacturing Novel Encapsulated 2D Materials.

Bilayer graphene (BLG) has recently been used as a tool to stabilize encapsulated single sheets of various layered materials and tune their properties. It was also discovered that the protecting action of graphene sheets makes it possible to synthesize completely new two-dimensional materials (2DMs) inside the BLG by intercalating various atoms and molecules. In comparison to the bulk graphite, BLG allows for easier intercalation and a much larger increase in the interlayer separation of the sheets. Moreover, it enables studying the atomic structure of the intercalated 2DM by using high-resolution transmission electron microscopy. In this review, we summarize the recent progress in this area, with a special focus on new materials created inside BLG. We compare the experimental findings with the theoretical predictions, pay special attention to the discrepancies, and outline the challenges in the field. Finally, we discuss unique opportunities offered by intercalation into 2DMs beyond graphene and their heterostructures.

Heat Stress Metrics, Trends, and Extremes in the Southeastern United States

Abstract Humid heat and associated heat stress have increased in frequency, intensity, and duration across the globe, particularly at lower latitudes. One of the more robust metrics for heat stress impacts on the human body is wet-bulb globe temperature (WBGT), because it incorporates temperature, humidity, wind speed, and solar radiation. WBGT can typically only be measured using nonstandard instrumentation (e.g., black globe thermometers). However, estimation formulas have been developed to calculate WBGT using standard surface meteorological variables. This study evaluates several WBGT estimation formulas for the southeastern United States using North Carolina Environment and Climate Observing Network (ECONet) and U.S. Military measurement campaign data as verification. The estimation algorithm with the smallest mean absolute error was subsequently chosen to evaluate summer WBGT trends and extremes at 39 ASOS stations with long continuous (1950–2023) data records. Trend results showed that summer WBGT has increased throughout much of the southeastern United States, with larger increases at night than during the day. Although there were some surprisingly large WBGT trends at higher elevation locations far from coastlines, the greatest increases were predominantly located in the Florida Peninsula and Louisiana. Increases in the intensity and frequency of extreme (90th percentile) WBGTs were particularly stark in large coastal urban centers (e.g., New Orleans, Tampa, and Miami). Some locations like New Orleans and Tampa have experienced more than two additional extreme heat stress days and nights per decade since 1950, with an exponential escalation in the number of extreme summer nights during the most recent decade. Significance Statement Humid heat and associated heat stress pose threats to health in the moist subtropical climate of the southeastern United States. Wet-bulb globe temperature (WBGT) is a robust metric for heat stress but must be estimated using complex algorithms. We first evaluated the accuracy of three WBGT algorithms in the southeastern United States, using measured verification data. Subsequently, we used the most accurate algorithm to investigate WBGT trends and extremes since 1950 in 39 cities. Results showed that summer heat stress has increased throughout the region, especially at night. Increases in the intensity and frequency of extreme heat stress were most prevalent at urban coastal locations in Florida and Louisiana, emphasizing the impacts of increased urbanization and evaporation on heat stress.

The Role of TandemHeartTM combined with ProtekDuoTM as Right Ventricular Support Device: A Simulation Approach

Background and ObjectiveRight ventricular failure increases short-term mortality in the setting of acute myocardial infarction, cardiogenic shock, advanced left-sided heart failure and pulmonary hypertension. Percutaneous and surgically implanted right ventricular assist devices (RVAD) have been investigated in different clinical settings. The use of the ProtekDuoTM is currently a promising approach due to its features such as groin-free approach leading to early mobilisation, easy percutaneous deployment, compatibility with different pumps and oxygenators, and adaptability to different configurations. The aim of this work was to simulate the behaviour of the TandemHeartTM pump applied “in series” and “in parallel“ mode and the combination of TandemHeartTM and ProtekDuoTM cannula as RVAD using CARDIOSIM© software simulator platform. MethodsTo achieve our aim, two new modules have been implemented in the software. The first module simulated the TandemHeartTM pump in RVAD configuration, both as a right atrial-pulmonary arterial and a right ventricular-pulmonary arterial connection, driven by four different rotational speeds. The second module reproduced the behaviour of the ProtekDuoTM cannula plus TandemHeartTM. ResultsThe effects induced on the main haemodynamic and energetic variables were analysed for both the right atrial-pulmonary arterial and right ventricular-pulmonary arterial configuration with different pump rotational speed and following Milrinone administration. The TandemHeartTM increased right ventricular end systolic volume by 10%, larger increases were evident for higher speeds (6000 and 7500 rpm) and connections with 21-Fr inflow and 17-Fr outflow cannula, respectively. Both TandemHeartTM and ProtekDuoTM support increased left ventricular preload. When different RVAD settings were used, Milrinone therapy increased the left ventricular pressure-volume area and decreased the right pressure-volume area slightly. A reduction in oxygen consumption (demand) was observed with reduced right stroke work and pressure volume area and increased oxygen supply (coronary blood flow). ConclusionsThe outcome of our simulations confirms the effective haemodynamic assistance provided by the ProtekDuoTM as observed in the acute clinical setting. A simulation approach based on pressure-volume analysis combined with modified time-varying elastance and lumped-parameter modelling remains a suitable tool for clinical applications.

Effects of nonlinearity on the crest shape of extreme irregular sea waves: Nonlinear harmonic separation and analysis

This work highlights the effects of nonlinearity on the crest shape of extreme directional water wave events in infinite and finite water depths. HOS-ocean, a High-Order Spectral code developed for solving the deterministic propagation of nonlinear wavefields in open ocean [Ducrozet et al., “HOS-ocean: Open-source solver for nonlinear waves in open ocean based on High-Order Spectral method,” Comput. Phys. Commun. 203, 245–254 (2016)], is used for comparisons with linear simulations. Nonlinear wave harmonics were extracted combining and extending previous methods [Fitzgerald et al., “Phase manipulation and the harmonic components of ringing forces on a surface-piercing column,” Proc. R. Soc. A 470, 20130847 (2014) and Hann et al., “A new set of focused wave linear combinations to extract non-linear wave harmonics,” in Proceedings of 29th International Workshop on Water Waves and Floating Bodies, 2014], showing the contribution of various orders of nonlinearity. The work shows that “walls of water,” [Adcock et al., “Nonlinear dynamics of wave-groups in random seas: Unexpected walls of water in the open ocean,” Proc. R. Soc. A 471, 20150660 (2015) and Adcock et al., “On the shape of large wave-groups on deep water—The influence of bandwidth and spreading,” Phys. Fluids 28, 106601 (2016)], a significant increase in the crest width, are also formulated in finite water depths. Mainly responsible for this is the first order harmonic, with significant energy transfers away from components propagating at an angle, which are more pronounced in finite water depths. As nonlinearity increases, higher order harmonics (&amp;gt;second) become, as expected, more significant. In deep water, rapid energy transfers lead to a broadening of the spectrum which is reflected in the increase in the first order amplitude sum and hence increased crest elevations at the point of the large event. However, in finite water depths, energy transfers are gradually leading to a narrowing of the spectrum around the spectral peak and to a general broadening of the spectrum at the higher harmonics; reflected in the significant decrease in the first order amplitude sum and hence a decrease in crest elevations at the point of the large event, also aided by the larger increase in the out-of-phase difference terms (zeroth harmonic).

Post-acute COVID-19 syndrome: prevalence of peripheral microvascular endothelial dysfunction and associations with NT-proBNP dynamics

BackgroundPost-acute COVID-19 syndrome (PACS) has been linked to microvascular endothelial dysfunction as a potential underlying pathomechanism and can manifest even following a mild course of the initial infection. Prevalence of microvascular endothelial dysfunction and circulating natriuretic peptides in such PACS patients remains unknown. Methods and resultsThis prospective, cross-sectional cohort study enrolled 92 patients (82% females, median age 48 years) with PACS. Reactive hyperemia index (RHI) was evaluated with peripheral arterial tonometry where <1.67 was defined as microvascular endothelial dysfunction, 1.67-2.0 impaired- and >2 normal endothelial function, on average 31 months after the acute infection. N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were collected at two different time points within over 1-year span. In total, 41% of PACS subjects had microvascular endothelial dysfunction and 20% had impaired RHI. No major differences in clinical characteristics, routine chemistry laboratory testing or symptom burden were observed across the groups. Only subjects with microvascular endothelial dysfunction and impaired endothelial function had a significant increase in NT-proBNP levels over time and those with larger increase in NT-proBNP had significantly lower RHI. There was a significant correlation between relative or absolute increase in NT-proBNP and RHI, which remained significant in a multivariable adjusted linear regression. ConclusionsPeripheral microvascular endothelial dysfunction was prevalent in a symptomatic PACS population long after recovery from a mild acute infection. Increases in NT-proBNP levels were associated with microvascular endothelial dysfunction, suggesting a link between and providing a foundation for future studies on post viral microvascular endothelial dysfunction in PACS.