Significant Increase In Mortality Research Articles

DNA methylase 1 influences temperature responses and development in the invasive pest Tuta absoluta.

DNA methylase 1 (Dnmt1) is an important regulatory factor associated with biochemical signals required for insect development. It responds to changes in the environment and triggers phenotypic plasticity. Meanwhile, Tuta absolutaMeyrick (Lepidoptera: Gelechiidae)-a destructive invasive pest-can rapidly invade and adapt to different habitats; however, the role of Dnmt1 in this organism has not been elucidated. Accordingly, this study investigates the mechanism(s) underlying the rapid adaptation of Tuta absoluta to temperature stress. Potential regulatory genes were screened via RNAi (RNA interference), and the DNA methylase in Tuta absoluta was cloned by RACE (Rapid amplification of cDNA ends). TaDnmt1 was identified as a potential regulatory gene via bioinformatics; its expression was evaluated in response to temperature stress and during different development stages using real-time polymerase chain reaction. Results revealed that TaDnmt1 participates in hot/cold tolerance, temperature preference and larval development. The full-length cDNA sequence of TaDnmt1 is 3765 bp and encodes a 1254 kDa protein with typical Dnmt1 node-conserved structural features and six conserved DNA-binding active motifs. Moreover, TaDnmt1 expression is significantly altered by temperature stress treatments and within different development stages. Hence, TaDnmt1 likely contributes to temperature responses and organismal development. Furthermore, after treating with double-stranded RNA and exposing Tuta absoluta to 35°C heat shock or -12°C cold shock for 1 h, the survival rate significantly decreases; the preferred temperature is 2°C lower than that of the control group. In addition, the epidermal segments become enlarged and irregularly folded while the surface dries up. This results in a significant increase in larval mortality (57%) and a decrease in pupation (49.3%) and eclosion (50.9%) rates. Hence, TaDnmt1 contributes to temperature stress responses and temperature perception, as well as organismal growth and development, via DNA methylation regulation. These findings suggest that the rapid geographic expansion of T absoluta has been closely associated with TaDnmt1-mediated temperature tolerance. This study advances the research on 'thermos Dnmt' and provides a potential target for RNAi-driven regulation of Tuta absoluta.

Epidemiological characteristics of asthma-COPD overlap, its association with all-cause mortality, and the mediating role of depressive symptoms: evidence from NHANES 2005–2018

BackgroundAsthma-COPD overlap (ACO) is a distinct and intricate respiratory condition that requires specific attention and management. The objective of this cohort study was to examine the epidemiological characteristics of ACO, explore the association between ACO and all-cause mortality, and investigate the potential mediating role of depressive symptoms in this association.MethodsThis retrospective cohort study used data from the National Health and Nutrition Examination Survey (NHANES) 2005–2018 and National Death Index (NDI) 2019. A total of 22,745 participants were included: 705 with ACO, 2352 with asthma-only, 853 with COPD-only, and 18,835 without asthma or COPD. The non-ACO group (N = 22,040) referred to the individuals without ACO. Statistical tests were employed to assess differences in some characteristics between the ACO group and the other groups. Cox proportional hazards models were applied to evaluate the relationship between ACO and all-cause mortality, estimating hazard ratios (HR) with 95% confidence intervals. Mediation analysis was conducted to investigate the potential mediating effects of depressive symptoms on the association of ACO with all-cause mortality.ResultsThe prevalence of ACO was 3.10% in our study population. Compared to the non-ACO participants, the ACO participants exhibited significantly different characteristics, including higher age, a lower family income-to-poverty ratio, a higher body mass index, higher rates of comorbidities i.e., hypertension, diabetes, hyperlipidemia, cardiovascular disease, and cancer, poorer dietary habits, and a higher rate of depressive disorders. Compared to the participants without ACO, the participants with ACO exhibited a significant increase in all-cause mortality (HR = 1.908, 95%CI 1.578–1.307, p < 0.001). The proportions mediated by depressive symptoms for ACO -associated all-cause mortality were 8.13% (CI: 4.22%-14.00%, p < 0.001).ConclusionsThis study revealed a strong relationship between ACO and all-cause mortality and uncovered a potential psychological mechanism underlying this relationship. Our study indicates the possible necessity of offering comprehensive care to ACO patients, encompassing early detection, lifestyle guidance, and mental health support. Nevertheless, due to the limitations in the study design and the dataset, the results should be interpreted with caution.

Role of CYP9E2 and a long non-coding RNA gene in resistance to a spinosad insecticide in the Colorado potato beetle, Leptinotarsa decemlineata.

Spinosads are insecticides used to control insect pests, especially in organic farming where limited tools for pest management exist. However, resistance has developed to spinosads in economically important pests, including Colorado potato beetle (CPB), Leptinotarsa decemlineata. In this study, we used bioassays to determine spinosad sensitivity of two field populations of CPB, one from an organic farm exposed exclusively to spinosad and one from a conventional farm exposed to a variety of insecticides, and a reference insecticide naïve population. We found the field populations exhibited significant levels of resistance compared with the sensitive population. Then, we compared transcriptome profiles between the two field populations to identify genes associated primarily with spinosad resistance and found a cytochrome P450, CYP9E2, and a long non-coding RNA gene, lncRNA-2, were upregulated in the exclusively spinosad-exposed population. Knock-down of these two genes simultaneously in beetles of the spinosad-exposed population using RNA interference (RNAi) resulted in a significant increase in mortality when gene knock-down was followed by spinosad exposure, whereas single knock-downs of each gene produced smaller effects. In addition, knock-down of the lncRNA-2 gene individually resulted in significant reduction in CYP9E2 transcripts. Finally, in silico analysis using an RNA-RNA interaction tool revealed that CYP9E2 mRNA contains multiple binding sites for the lncRNA-2 transcript. Our results imply that CYP9E2 and lncRNA-2 jointly contribute to spinosad resistance in CPB, and lncRNA-2 is involved in regulation of CYP9E2 expression. These results provide evidence that metabolic resistance, driven by overexpression of CYP and lncRNA genes, contributes to spinosad resistance in CPB.

#2980 The natural history of urinary tract infections in kidney transplant recipients

Abstract Background and Aims Urinary tract infections (UTIs) can occur following kidney transplantation, but research on infection rates and outcomes is inconclusive. We therefore aimed to provide a comprehensive understanding of the natural history of UTIs and the impact on long-term outcomes. Method We performed a single-centre cohort study of kidney-only transplant recipients at the Glasgow Transplant Unit, UK. A standardised protocol for UTI screening and treatment was in use and only treated UTIs were included. We studied the first two years post-transplant as this is the time when UTIs are most likely to occur. Patients were categorised into 3 groups based on number of UTIs: no UTIs, 1-2 UTIs and ≥3 UTIs. Furthermore, patients with highly recurrent UTIs defined as ≥10 UTIs in the first 2 years were compiled and analysed. Proportional odds logistic regression was performed to identify risk factors for having ≥3 UTIs, with adjustment for age, sex, primary renal diagnosis, donor type (live donor, deceased heart beating, deceased non-heart beating) and induction immunosuppression. Results Amongst 1412 transplant recipients studied over a nine-year period, the mean age was 48 years and 563 (39.9%) were female. 1169 (82.8%) of recipients experienced no UTIs, 180 (12.7%) had 1-2 UTIs, and 63 (4.5%) had ≥3 UTIs (Fig. 1). The key risk factors for developing ≥3 UTIs were female sex: adjusted odds ratio (aOR) 1.50 (95% confidence interval 1.13-1.99), induction with anti-thymocyte globulin (ATG): aOR 6.60 (3.05-14.05), and age: aOR for each one-year increase 1.01 (1.00-1.02). There were no primary renal diagnoses (PRD) that demonstrated a significant association with ≥3 UTIs. However, individuals with tubulointerstitial disease, a group which includes structural abnormalities of the urinary tract and reflux nephropathy as a considerable proportion, showed a trend towards heightened risk: aOR 1.47 (0.97-2.22, reference group glomerulonephritis). Recipients with ≥3 UTIs had lower estimated glomerular filtration rates (eGFRs) at two years compared to the no UTI group (49.7 vs. 59.2mL/min/1.73 m2, respectively). However, there was no significant increase in mortality or graft loss between the three groups. In the group of patients with highly recurrent UTIs, consisting of 14 patients (0.01%), we observed that 3 (21%) had a PRD of reflux nephropathy, while 5 (35%) had underlying structural abnormalities of the native renal tract as a PRD. Further to this 5 (35%) of the patients received ATG induction and 5 (35%) patients had a previous transplant. Conclusion We describe a low rate of UTIs requiring treatment in the first two years after kidney transplantation. Females, older recipients and those given ATG induction were at increased risk of recurrent UTIs. There was no impact of UTIs on graft loss or patient mortality. However, eGFR at two years post-transplant was lower amongst those with recurrent UTIs. We also observed that for the patients with highly recurrent UTIs, ATG induction, previous transplants, reflux nephropathy and structural abnormalities of native renal tract may be a risk factor. Recipients at highest risk of UTIs should therefore be screened for UTIs and interventions to reduce this risk should be considered

Evaluating social protection mitigation effects on HIV/AIDS and Tuberculosis through a mathematical modelling study

The global economic downturn due to the COVID-19 pandemic, war in Ukraine, and worldwide inflation surge may have a profound impact on poverty-related infectious diseases, especially in low-and middle-income countries (LMICs). In this work, we developed mathematical models for HIV/AIDS and Tuberculosis (TB) in Brazil, one of the largest and most unequal LMICs, incorporating poverty rates and temporal dynamics to evaluate and forecast the impact of the increase in poverty due to the economic crisis, and estimate the mitigation effects of alternative poverty-reduction policies on the incidence and mortality from AIDS and TB up to 2030. Three main intervention scenarios were simulated—an economic crisis followed by the implementation of social protection policies with none, moderate, or strong coverage—evaluating the incidence and mortality from AIDS and TB. Without social protection policies to mitigate the impact of the economic crisis, the burden of HIV/AIDS and TB would be significantly larger over the next decade, being responsible in 2030 for an incidence 13% (95% CI 4–31%) and mortality 21% (95% CI 12–34%) higher for HIV/AIDS, and an incidence 16% (95% CI 10–25%) and mortality 22% (95% CI 15–31%) higher for TB, if compared with a scenario of moderate social protection. These differences would be significantly larger if compared with a scenario of strong social protection, resulting in more than 230,000 cases and 34,000 deaths from AIDS and TB averted over the next decade in Brazil. Using a comprehensive approach, that integrated economic forecasting with mathematical and epidemiological models, we were able to show the importance of implementing robust social protection policies to avert a significant increase in incidence and mortality from AIDS and TB during the current global economic downturn.

Overactivated MX1 Positive Natural Killer Cells Promote the Progression of Sepsis-Induced Acute Respiratory Distress Syndrome.

Natural killer (NK) cells are key regulators of immune defense in sepsis-induced acute respiratory distress syndrome (ARDS), yet the characteristics of NK cell clusters in ARDS remain poorly understood. A prospective and observational study enrolled septic patients with ARDS or not was conducted to determine the percentage of NK cells via flow cytometry. The transcriptomes of peripheral blood mononuclear cells (PBMCs) from healthy controls, patients with sepsis only, and patients with sepsis-induced ARDS were profiled. Vitro experiments were performed to confirm the mechanism mediating MX1+NK cell infiltration. A total of 115 septic patients were analyzed, among whom 63 patients developed ARDS and 52 patients did not. Decreased NK percentages were found in sepsis with ARDS patients (%, 7.46±4.40 vs 11.65±6.88, P=0.0001) compared with sepsis-only patients. A lower percentage of NK cells showed a significant increase in 28-day mortality. Single-cell sequencing analysis revealed distinct characteristics of NK cells in sepsis-induced ARDS, notably the identification of a unique cluster defined as MX1+NK cells. Flow cytometry analysis showed an elevated percentage of MX1+NK cells specifically in individuals with sepsis-induced ARDS, compared with patients with sepsis only. Pseudo-time analysis showed that MX1+NK cells were characterized by upregulation of type I interferon-induced genes and other pro-inflammatory genes. MX1+NK cells can respond to type I interferons and secrete type I interferons themselves. Ligand-receptor interaction analysis also revealed extensive interaction between MX1+NK cells and T/B cells, leading to an uncontrolled inflammatory response in ARDS. MX1+NK cells can respond to type I interferons and secrete type I interferons themselves, promoting the development of sepsis-induced ARDS. Interfering with the infiltration of MX1+NK cells could be a therapeutic approach for this disease. Due to the limited sample size, a larger sample size was needed for further exploration.

Toxic effects of acaricide fenazaquin on development, hemolymph metabolome, and gut microbiome of honeybee (Apis mellifera) larvae

Fenazaquin, a potent insecticide widely used to control phytophagous mites, has recently emerged as a potential solution for managing Varroa destructor mites in honeybees. However, the comprehensive impact of fenazaquin on honeybee health remains insufficiently understood. Our current study investigated the acute and chronic toxicity of fenazaquin to honeybee larvae, along with its influence on larval hemolymph metabolism and gut microbiota. Results showed that the acute median lethal dose (LD50) of fenazaquin for honeybee larvae was 1.786 μg/larva, and the chronic LD50 was 1.213 μg/larva. Although chronic exposure to low doses of fenazaquin exhibited no significant effect on larval development, increasing doses of fenazaquin resulted in significant increases in larval mortality, developmental time, and deformity rates. At the metabolic level, high doses of fenazaquin inhibited nucleotide, purine, and lipid metabolism pathways in the larval hemolymph, leading to energy metabolism disorders and physiological dysfunction. Furthermore, high doses of fenazaquin reduced gut microbial diversity and abundance, characterized by decreased relative abundance of functional gut bacterium Lactobacillus kunkeei and increased pathogenic bacterium Melissococcus plutonius. The disrupted gut microbiota, combined with the observed gut tissue damage, could potentially impair food digestion and nutrient absorption in the larvae. Our results provide valuable insights into the complex and diverse effects of fenazaquin on honeybee larvae, establishing an important theoretical basis for applying fenazaquin in beekeeping.

Impact of Povidone Application to Nares in Addition to Chlorhexidine Bath in Critically Ill Patients on Nosocomial Bacteremia and Central Line Blood Stream Infection.

Nosocomial Methicillin-resistant Staphylococcus aureus (MRSA) bacteremia results in a significant increase in morbidity and mortality in hospitalized patients. We aimed to analyze the impact of applying 10% povidone iodine (PI) twice daily to both nares in addition to chlorhexidine (CHG) bathing on nosocomial (MRSA) bacteremia in critically ill patients. A quality improvement study was completed with pre and post-design. The study period was from January 2018 until February 2020 and February 2021 and June 2021. The control period (from January 2018 to May 2019) consisted of CHG bathing alone, and in the intervention period, we added 10% PI to the nares of critically ill patients. Our primary outcome is rates of nosocomial MRSA bacteremia, and our secondary outcome is central line associated blood stream infection (CLABSI) and potential cost savings. There were no significant differences in rates of MRSA bacteremia in critically ill patients. Nosocomial MRSA bacteremia was significantly lower during the intervention period on medical/surgical areas (MSA). CLABSIs were significantly lower during the intervention period in critically ill patients. There were no Staphylococcus aureus CLABSIs in critical care area (CCA)during the intervention period. The intervention showed potential significant cost savings. The application of 10% povidone iodine twice a day in addition to CHG bathing resulted in a significant decrease in CLABSIs in critically ill patients and a reduction in nosocomial MRSA in the non-intervention areas. Further trials are needed to tease out individual patients who will benefit from the intervention.

Association between inflammation-based prognostic markers and mortality after hip replacement

We aimed to evaluate the association between inflammation-based prognostic markers and mortality after hip replacement. From March 2010 to June 2020, we identified 5,369 consecutive adult patients undergoing hip replacement with C-reactive protein (CRP), albumin, and complete blood count measured within six months before surgery. Receiver operating characteristic (ROC) curves were generated to evaluate predictabilities and estimate thresholds of CRP-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR). Patients were divided according to threshold, and mortality risk was compared. The primary outcome was one-year mortality, and overall mortality was also analyzed. One-year mortality was 2.9%. Receiver operating characteristics analysis revealed areas under the curve of 0.838, 0.832, 0.701, and 0.732 for CAR, NLR, PLR, and modified Glasgow Prognostic Score, respectively. The estimated thresholds were 2.10, 3.16, and 11.77 for CAR, NLR, and PLR, respectively. According to the estimated threshold, high CAR and NLR were associated with higher one-year mortality after adjustment (1.0% vs. 11.7%; HR = 2.16; 95% CI 1.32–3.52; p = 0.002 for CAR and 0.8% vs. 9.6%; HR = 2.05; 95% CI 1.24–3.39; p = 0.01 for NLR), but PLR did not show a significant mortality increase (1.4% vs. 7.4%; HR = 1.12; 95% CI 0.77–1.63; p = 0.57). Our study demonstrated associations of preoperative levels of CAR and NLR with postoperative mortality in patients undergoing hip replacement. Our findings may be helpful in predicting mortality in patients undergoing hip replacement.

Flupyradifurone negatively affects survival, physical condition and mobility in the two-spotted lady beetle (Adalia bipunctata)

Lady beetles play a crucial role in natural ecosystems and agricultural settings. Unfortunately, these insects and more specifically the two-spotted lady beetle (Adalia bipunctata) are currently facing a severe decline in populations due to various stressors, with pesticide exposure being a significant threat. Flupyradifurone is a relatively newly introduced insecticide and as existing research is mainly elucidating its effects on bees there remains a limited understanding of its effects on non-hymenopteran insects, including lady beetles.In this study we investigated the impact of acute orally applied flupyradifurone doses on survival and sublethal parameters such as physical condition and mobility on A. bipunctata. Our findings revealed a significant increase in mortality among individuals subjected to flupyradifurone doses of 19 ng/individual (corresponding to >1.5–2.0 ng active substance (a.s.)/mg body weight (bw). The calculated LD50 of flupyradifurone at 48 h was 2.11 ng a.s./mg bw corresponding to an amount of 26.38 ng/individual. Sublethal consequences were observable immediately after pesticide application. Even at doses as low as 2 ng/individual (corresponding to >0.0–0.5 ng a.s./mg bw), flupyradifurone induced trembling and temporary immobility in treated animals. Furthermore, pesticide intoxication led to hypoactivity, with less distance covered and a decline in straightness of locomotion.In conclusion, our study underscores the harmful effects of flupyradifurone on the two-spotted lady beetle at doses notably lower than those affecting bees. These findings stress the importance of additional research to attain a more holistic understanding of pesticide impacts not only on a broader range of non-target arthropods species, but also on various exposure routes as well as lethal and sublethal effects.

Prognostic Impact of Sinus Rhythm in Atrial Fibrillation Patients: Separating Rhythm Outcomes From Randomized Strategy Findings From the CABANA Trial.

Clinically detected atrial fibrillation (AF) is associated with a significant increase in mortality and other adverse cardiovascular events. Since the advent of effective methods for AF rhythm control, investigators have attempted to determine how much these adverse prognostic AF effects could be mitigated by the restoration of sinus rhythm (SR) and whether the method used mattered. The CABANA trial (Catheter Ablation versus Antiarrhythmic Drug Therapy for Atrial Fibrillation) randomized 2204 AF patients to ablation versus drug therapy, of which 1240 patients were monitored in follow-up using the CABANA ECG rhythm monitoring system. To assess the prognostic benefits of SR, we performed a prespecified analysis using Cox survival modeling with heart rhythm as a time-dependent variable and randomized treatment group as a stratification factor. In the 1240 patient study cohort, 883 (71.2%) had documented AF at some point during their postblanking follow-up. Among the 883 patients, 671 (76.0%) experienced AF within the first year of postblanking follow-up, and 212 (24.0%) experienced their first AF after ≥1 year of postblanking follow-up. The primary CABANA end point (death, disabling stroke, serious bleeding, or cardiac arrest) occurred in 95 (10.8%) of the 883 patients with documented AF and in 29 (8.1%) of the 357 patients with no AF recorded during follow-up. In multivariable time-dependent analysis, the presence of SR (compared with non-SR) was associated with a significantly reduced risk of the primary end point (adjusted hazard ratio, 0.57 [95% CI, 0.38-0.85]; P=0.006; independent of treatment strategy [ablation versus drugs]). Corresponding results for all-cause mortality were adjusted hazard ratio of 0.59 [95% CI, 0.35-1.01]; P=0.053). In patients in the CABANA trial with detailed long-term rhythm follow-up, increased time in SR was associated with a clinically consequential decrease in mortality and other adverse prognostic events. The predictive value of SR was independent of the therapeutic approach responsible for reducing the burden of detectable AF. URL: https://clinicaltrials.gov; Unique Identifier: NCT00911508.

Association of device detected atrial and ventricular tachyarrhythmia with adverse events in patients with an implantable cardioverter-defibrillator.

Heart failure patients with a history of atrial fibrillation (AF) and ventricular tachycardia/ventricular fibrillation (VT/VF) are known to have worse outcomes. However, there are limited data on the temporal relationship between development of these arrhythmias and the risk of subsequent congestive heart failure (CHF) exacerbation and death. The study cohort comprised 5511 patients implanted with an implantable cardioverter-defibrillator (ICD) in landmark clinical trials (MADIT-II, MADIT-RISK, MADIT-CRT, MADIT-RIT, and RAID) who were in sinus rhythm at enrollment. Multivariate cox analysis was performed to evaluate the time-dependent association between development of in-trial device detected AF and VT/VF with subsequent CHF exacerbation and death. Multivariate analysis showed that AF occurrence and VT/VF occurrence were both associated with a similar magnitude of risk for subsequent CHF exacerbation (HR = 1.73 and 1.87 respectively, p < .001 for both). In contrast, only in-trial VT/VF was associated with a significant > two-fold increase in the risk of subsequent mortality (HR = 2.13, p < .001) whereas AF occurrence was not associated with a significant mortality increase after adjustment for in-trial VT/VF (HR = 1.36, p = .096). Our findings from a large cohort of ICD recipients enrolled in landmark clinical trials show that device detected AF and VT/VF can be used to identify patients with increased risk for CHF exacerbation and mortality. These findings suggest a need for early intervention in CHF patients who develop device-detected atrial and ventricular tachyarrhythmias.

The association between restricted activity and patient outcomes in older adults: systematic literature review and meta-analysis

BackgroundRestricted activity is a potential early marker of declining health in older adults. Previous studies of this association with patient outcomes have been inconclusive. This review aimed to evaluate the extent to which restricted activity is associated with decline in health.MethodsA search was conducted for studies including people over 65 years old which investigated the association between measures of restricted activity and hospitalisation, cognitive decline, and mortality. Following data extraction by two reviewers, eligible studies were summarised using Inverse Variance Heterogeneity meta-analysis.ResultsThe search identified 8,434 unique publications, with 11 eligible studies. Three measures of restricted activity were identified: bed rest, restricted movement, and dependency for activities of daily living (ADL). Three studies looked at hospitalisations, with two finding a significant association with bed rest or restricted movement and one showing no evidence of an association. Restricted activity was associated with a significant increase in mortality across all three measures (bed rest odds ratio [OR] 6.34, 95%CI 2.51–16.02, I2 = 76%; restricted movement OR 5.38 95%CI 2.60–11.13, I2 = 69%; general ADL dependency OR 4.65 95%CI 2.25–9.26, I2 = 84%). The significant heterogeneity observed could not be explained by restricting the analysis by length of follow-up, or measure of restricted activity. No meta-analysis was conducted on the limited evidence for cognitive decline outcomes.ConclusionsLimited studies have considered the prognostic value of restricted activity in terms of predicting future declining health. Current evidence suggests restricted activity is associated with hospitalisation and mortality, and therefore could identify a group for whom early intervention might be possible.

Effects of developmental exposure to individual and combined PFAS on development and behavioral stress responses in larval zebrafish

Per- and polyfluoroalkyl substances (PFAS) are a class of synthetic chemicals known for their widespread use and persistence in the environment. Laboratory and epidemiological studies investigating these compounds have signaled their neurotoxic and endocrine-disrupting propensities, prompting further research into their effects on behavioral stress responses and their potential role as risk factors for stress-related disorders such as anxiety and depression. This study elucidates the ramifications of early developmental exposures to individual and combined PFAS on the development and behavioral stress responses of larval zebrafish (Danio rerio), an established model in toxicological research. Wild-type zebrafish embryos were enzymatically dechorionated and exposed to PFOS, PFOA, PFHxS, and PFHxA between 6 and 120 h post-fertilization (hpf). We targeted environmentally relevant concentrations stemming from the USEPA 2016 Hazard Advisory Limit (HAL, 0.07 μg/L) and folds higher (0.35, 0.7, 1.75, and 3.5 μg/L). Evaluations at 120 hpf encompassed mortality, overall development, developmental defects, and larval activity both at baseline stress levels and following exposure to acute stressors (acoustic and visual). Larval exposure to PFOA, PFOS, or PFHxS (0.07 μg/L or higher) elicited significant increases in mortality rates, which capped at 23.1%. Exposure to individual chemicals resulted in limited effects on overall development but increased the prevalence of developmental defects in the body axis, swim bladder, pigmentation, and eyes, as well as the prevalence of yolk sac and pericardial edemas. Larval activity at baseline stress levels and following exposure to acute stimuli was significantly altered. Combined exposure to all four chemicals intensified the breadth of developmental and behavioral alterations, suggesting possible additive or synergistic effects. Our findings shed light on the developmental and neurobehavioral disturbances associated with developmental exposure to PFAS at environmentally relevant concentrations, the added risks of combined exposures to these chemicals, and their possible role as environmental risk factors for stress-related disorders.

Outcomes and predictors of left ventricle recovery in patients with severe left ventricular dysfunction undergoing transcatheter aortic valve implantation.

Data on the likelihood of left ventricle (LV) recovery in patients with severe LV dysfunction and severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI) and its prognostic value are limited. We aimed to assess the likelihood of LV recovery following TAVI, examine its association with midterm mortality, and identify independent predictors of LV function. In our multicentre registry of 17 TAVI centres in Western Europe and Israel, patients were stratified by baseline LV function (ejection fraction [EF] >/≤30%) and LV response: no LV recovery, LV recovery (EF increase ≥10%), and LV normalisation (EF ≥50% post-TAVI). Our analysis included 10,872 patients; baseline EF was ≤30% in 914 (8.4%) patients and >30% in 9,958 (91.6%) patients. The LV recovered in 544 (59.5%) patients, including 244 (26.7%) patients whose LV function normalised completely (EF >50%). Three-year mortality for patients without severe LV dysfunction at baseline was 29.4%. Compared to this, no LV recovery was associated with a significant increase in mortality (adjusted hazard ratio 1.32; p<0.001). Patients with similar LV function post-TAVI had similar rates of 3-year mortality, regardless of their baseline LV function. Three variables were associated with a higher likelihood of LV recovery following TAVI: no previous myocardial infarction (MI), estimated glomerular filtration rate >60 mL/min, and mean aortic valve gradient (mAVG) (expressed either as a continuous variable or as a binary variable using the standard low-flow, low-gradient aortic stenosis [AS] definition). LV recovery following TAVI and the extent of this recovery are major determinants of midterm mortality in patients with severe AS and severe LV dysfunction undergoing TAVI. Patients with no previous MI and those with an mAVG >40 mmHg show the best results following TAVI, which are at least equivalent to those for patients without severe LV dysfunction. (ClinicalTrials.gov: NCT04031274).

IJCM_101A: Prevalence of postoperative delirium in geriatric patients with hip fracture.

Background: Geriatric hip fractures are a major cause of concern globally and often a frequent reason for morbidity and mortality. Postoperative delirium (POD) is frequent but often under-diagnosed complication, especially after a major hip surgery. Some of the factors contributing to delirium are sepsis, dyselectrolytemia, elevated blood sugars, blood pressure fluctuation, constipation, and malnutrition. It very important to prevent delirium and to treat the underlying cause contributing to it. Objective: Prevalence of postoperative delirium in Geriatric patients with hip fracture and to determine various factors associated with it. Methodology: Prospective study Samples are collected from geriatric hip fracture patients admitted in a tertiary health care centre. Data regarding preoperative blood investigations, hypertension, and diabetes status, MNA (mini nutritional assessments) status, serum albumin, and serum electrolytes values were recorded. The Confusion Assessment Method tool (CAM) was used to diagnose delirium in the postoperative period. Results: 140 patients fulfilling the inclusion and exclusion criteria were admitted to the study. Among the one hundred and forty patients, forty-nine patients developed delirium. The incidence of delirium in the postoperative period was 35%. The percentage of patients developing delirium was directly proportional to their advancing age In these patients major risk factor associated with delirium was pain, constipation, urosepsis (fever), dyselectrolytemia, uncontrolled glycemic status and prolonged hospital stay (delayed rehabilitation) Conclusion: Delirium is a common feature in the post-operative period in the elderly patients associated with acute alteration in attention and cognitive impairment, which is responsible for the significant increase in both morbidity and mortality. Multiple factors predispose a patient to different forms of delirium. The reversible causes must be identified and treated promptly. A wider knowledge of pathophysiology and clinical awareness can help to counter the possible deleterious effects of delirium during the post-operative period.

Impact of duration of cardiopulmonary bypass on recovery after open heart surgery

Background: Objective of the study was to examine the impact of cardiopulmonary bypass (CPB) duration on recovery from cardiac surgery. Methods: This is an observational retrospective study. Data from adult cardiac surgical patients presented at Queen Alia Heart Institute (QAHI) in the duration between September 2023 and February 2024 was retrospectively analysed. The impact of CPB duration was examined. Patients were divided into groups according to CPB duration (0 to 60 minutes, 60 to 120 minutes, 120 to 180 minutes, 180 to 240 minutes and 240 to 300 minutes). For each group intra-operative and post-operative variable were examined. The intra-operative variables studied were need for blood transfusion, haemofiltration and intra-aortic balloon pump. The post-operative variables studied were duration of post-operative mechanical ventilation, intensive care unit (ICU) stay, hospitalization time and mortality. Results: Consecutive data of 202 adult cardiac surgical patients (34 females and 168 males) was analysed. Average age of patients was 57.149 years. Average duration of CPB was 109.9 minutes (ranged from 29 to 300 minutes). Half of the patients (50.5%) had CPB duration between 1 and 2 hours. Blood transfusion was needed in 88 patients (43.6%). Haemofiltration was used in 32 patients (15.8%) and intra-aortic balloon pump (IABP) was used in 29 patients (14.4%). The average postoperative time of mechanical ventilation was 34 hours and the average ICU stay was 5.5 days. Chest re-exploration was needed in 30 patients (15%). Hospital stay was on average 12 days and in-hospital mortality was witnessed in 20 patients (9.9%). Patients who had CPB for less than one hour (17.3%) had the lowest incidence of blood transfusion (37.1%), lowest incidence of haemofiltration (8.6%), low incidence of IABP use (11%). They also had lowest incidence of chest re-opening (5.7%), shortest time of postoperative mechanical ventilation (13 hours) and shortest ICU and hospital stay (4.1 and 8.5 days, respectively). There was a significant increase in postoperative sternal re-opening and postoperative mortality when the duration of CPB exceeded 3 hours. Conclusions: Duration of CPB is a key predictor of recovery and outcome of cardiac surgery. Shorter CPB time was associated with earlier extubation, less ICU stay and shorter hospitalisation time. Prolonged CPB was associated with higher rates of complications, delayed recovery, longer ICU stay, protracted hospitalisation and higher mortality rates.

The significance of light chronodestruction in the development of the embryotoxic effect in the experiment

Objective. To assess the significance of light chronodestruction in the development of the embryotoxic effect in the experiment. Materials and methods. The experiment was conducted on 60 female rats of the Wistar line. To assess the significance of chronodestruction in the development of embryotoxic effect, the uterus was isolated in the experiment, in which the number of implantation sites, the total number of embryos, the number of live and dead embryos, and the number of resorptions were estimated. The number of corpus luteum in the harvested ovaries was estimated. In addition, the mean embryo weight (g) and mean craniocaudal size (mm) were recorded. Indicators of embryotoxic effects of light deprivation were determined by pre- and post-implantation death, which was calculated in accordance with methodological recommendations. Results. Exposure to light deprivation reduces the number of implantation sites as of 7th, 14th and 21st days by 1,5-1,8 times, the total number of embryos by 1,6-1,8 times, the number of living embryos by 2,2-9 times and increases the number of dead embryos as of 14th and 21st days by 4-5,5 times, the number of resorptions – 1,6-11 times. The average craniocaudal size (mm) of embryos in experimental animals was recorded below control values by 1,5 times, 1,3 and 3,7 times by 7th, 14th, 21st days respectively. In females exposed to light deprivation, there was a significant increase in pre-implantation mortality by 35-41,8 times and post-implantation mortality by 7,2-20,4 times compared to the control. Conclusion. Light deprivation may have a negative effect on pregnancy and fetal development in female rats, which is confirmed by an increase in pre- and post-implantation mortality.

Radiological Parameters for the Detection of Pulmonary Hypertension in Severe Aortic Valve Stenosis and Their Influence on Mortality: Does Sex Matter?

Background: Echocardiography has long been established as the primary noninvasive method for diagnosing pulmonary hypertension (PH) prior to transcatheter aortic valve replacement (TAVR) in patients with severe aortic valve stenosis (AS). In recent years, radiological methods for diagnosing PH have been investigated. Measurements such as the computed tomography angiography (CTA)-derived pulmonary artery (PA) diameter and PA diameter/body surface area (PA/BSA) have shown promising results regarding their diagnostic strength. However, it has yet to be determined if a patient's sex has any impact on the effectiveness of these diagnostic measurements. Methods: In all, 271 patients (51.3% male, mean age 82.6 ± 4.8 years) with severe AS undergoing TAVR were separated into male and female groups. The cut-off values for the diagnosis of PH were calculated for the CTA-derived PA diameter and PA/BSA based on different systolic pulmonal artery pressure values (40-45-50 mmHg). Patients were then subclassified according to measurements above or below these PA diameters and PA/BSA cut-off values. A PA diameter ≥29.5 mm and PA/BSA ≥ 15.7 mm/m2 qualified for PH. The 1-5 year survival rate in these cohorts was further analyzed. Results: Patients with a PA diameter ≥29.5 mm showed a significantly higher 1 year mortality rate (p = 0.014). This observation could only be confirmed for the male sex (p = 0.018) and not for the female sex (p = 0.492). As for the PA/BSA, in patients over the cut-off value, no significant increase in mortality was noted in the overall cohort. However, the male patients showed increased 3 year (p = 0.048) and 5 year mortality rates (p = 0.033). Conclusions: The CTA-obtained PA diameter and PA/BSA are both useful in the diagnosis of PH and mortality risk stratification in patients with severe AS undergoing TAVR, especially in males. Male patients with PA ≥ 29.5 mm or PA/BSA ≥ 15.7 mm/m2 seem to be at a higher risk of death during follow-up after undergoing TAVR. In females, no such correlation was observed.

Impact of therapeutic hypothermia (whole body cooling) on severely asphyxiated term neonates: a prospective non-randomized comparative study in an Indian tertiary care setting

Background: Early application of Therapeutic Hypothermia within 6 hours of birth is neuroprotective. We aimed at examining whether therapeutic hypothermia alongside standard optimal intensive care improves immediate survival outcome and reduces neuro-disability. Methods: This was a prospective non-randomized study involving inborn and out born newborns admitted at NICU, carried out from March 2022 to December 2022. Eligible candidates were enrolled as cases and therapeutic hypothermia was offered while rest were included as a control group and monitored likewise for the overall survival and neurological outcome. These babies were followed up till 1 month and 3 months of age to assess neurological outcome. Results: In this study, a total of 47 patients were enrolled both from extramural and intramural NICU set ups. Of them, 22 patients were offered Therapeutic Hypothermia and 25 patients were given standard post asphyxia care. 7 out of 9 inborn patients and 3 out of 13 out born neonates who were offered therapeutic hypothermia survived whereas 5 out of 11 inborn and 4 out of 14 out born neonates who were offered standard post asphyxia care survived. Conclusions: Therapeutic hypothermia cannot be attributed to significant increase or decrease in mortality when compared with standard care group. No inference could be made about hypothermic neuroprotection in the follow up study. Overall survival outcome was better in inborn patients than that of outborn. Inborn neonates subjected to therapeutic hypothermia, showed a trend towards better survival than those given standard post asphyxia care.