Association of Various Optical Coherence Tomographic Patterns of Diabetic Macular Edema With Central Subfield Thickness and Visual Acuity: A Cross-Sectional Observational Study.

Introduction Diabetic macular edema (DME) is the most common and vision-threatening complication in diabetic patients with diabetic retinopathy (DR), especially in those with Type 2 diabetes mellitus. Optical coherence tomography (OCT) is a reliable tool most commonly used for assessing macular morphology and provides quantitative information on the macula. OCT also examines the outer retinal layers, which can predict visual outcomes. Thus, our study aims to identify the association of various OCT-detected DME morphological patterns with central subfield thickness (CST) and visual acuity. Materials and methods This is a cross-sectional observational study of 50 patients with DME detected on OCT who visited the Ophthalmology Department of Saveetha Medical College and Hospitals for a period of six months, from November 2023 to April 2024. A complete ocular examination, including best corrected visual acuity, scored with the logMAR scale, anterior segment examination, and fundus biomicroscopy using 90D and 78D lenses, was performed. Early Treatment of Diabetic Retinopathy Study (ETDRS) grading of DR into mild to very severe non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) was noted. Spectral-domain OCT was used to diagnose DME. The CST was measured, and DME was classified into four patterns: sponge-like retinal swelling (SLRS), cystoid macular edema (CME), subretinal fluid (SRF), and posterior hyaloid traction (PHT). Results In the present study, males represented 60%, and females represented 40%. The mean age of the patients was 58.07 ± 6.80 years, with a mean duration of diabetes of 11.91 ± 5.14 years. Of the 50 patients with 100 eyes, only 60 eyes showed DME on OCT. CME was the most common morphological pattern (37%), while the least common pattern was PHT (10%). No significant association was found between a specific morphological pattern and control of diabetes. The most common pattern observed was SLRS in moderate NPDR, CME in severe NPDR, SRF in very severe NPDR, and PHT in PDR. Very severe NPDR patients showed all patterns of DME, and the PHT pattern was observed only in very severe NPDR and PDR. The highest mean CST was observed in the very severe NPDR stage, and the least was in the moderate NPDR stage. The mean CST was highest in SRF patterns and lowest in SLRS patterns. The best mean visual acuity was observed in the SLRS pattern, while the worst mean visual acuity was observed in the SRF pattern, followed by the PHT pattern. Conclusion Our study highlights the importance of OCT in patients with diabetes, as OCT patterns of DME are critical for predicting visual outcomes in DR. Severe grades of DR are usually associated with SRF and PHT patterns. Since patients with SRF and PHT patterns have the worst visual outcomes, these patients, upon identification, need to be counseled about their poor visual prognosis. Those with less severe DR should be closely monitored and advised on effective diabetes control to prevent progression and protect their vision.

Capsaicin Promotes Apoptosis and Inhibits Cell Migration via the Tumor Necrosis Factor-Alpha (TNFα) and Nuclear Factor Kappa B (NFκB) Signaling Pathway in Oral Cancer Cells.

Background Oral squamous cell carcinoma (OSCC) is a highly prevalent cancer worldwide. Microbial infections, poor oral hygiene, and chronic viral infections such as human papillomavirus (HPV) contribute to its incidence. Capsaicin, known for its presence in chili peppers, has demonstrated potential antiproliferative effects in cancer cells. It operates by inducing programmed cell death, regulating the expression of transcription factors, halting cell cycle progression, and influencing growth signal transduction pathways. These findings suggest capsaicin's promising role as a candidate for further exploration in combating oral cancer. Aim This study intends to identify and evaluate the anticancer properties of capsaicin on oral cancer cells through in vitro investigations. Methodology Using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) technique, the cell viability of oral cancer cells treated with capsaicin was evaluated. Capsaicin was applied to the KB1 cells in a range of concentrations (25-150 µg/mL) over 24 hours. The morphological alterations of the cells were assessed using a phase contrast microscope. Nuclear factor kappa B (NFκB) and tumor necrosis factor-alpha (TNFα) were subjected to quantitative real-time polymerase chain reaction (PCR) gene expression analysis. To investigate nuclear morphological changes, oral cancer cells were stained with acridine orange/ethidium bromide (AO/EtBr). The apoptotic nuclei were visualized using a fluorescent microscope. A scratch wound healing test was performed to check for capsaicin's anti-migratory potential. Result In our investigation of oral cancer cells treated with capsaicin, there was a significant drop in cell viability between the control and treatment groups (p < 0.05). The inhibitory concentration (IC50) was found to be 74.4 µM/mL in oral cancer cells. Following treatment, fewer cells were present, and those that were present shriveled and exhibited cytoplasmic membrane blebbing. Under AO/EtBr staining, treated cells exhibited chromatin condensation and nuclear disintegration. Furthermore, the migration of capsaicin-treated cells was significantly lower than that of control cells. The results of gene expression analysis demonstrated a considerable downregulation of TNFα and NFκB following capsaicin administration. Conclusion The study's findings suggest that capsaicin may have anti-tumor properties in oral cancer cells. More research is desperately needed to fully understand the mechanism underlying capsaicin's anticancer potential and therapeutic applicability.

A Case Report on Acute Visual Loss With Ophthalmoplegia Following Spine Surgery.

Postoperative vision loss is an unusual but serious side effect that can occur after nonocular surgeries, particularly those involving the heart or spine. Various causes, including ischemic optic neuropathy, central retinal artery occlusion, central retinal vein occlusion, and ischemic orbital compartment syndrome, can cause this condition. Here, we present a case of a 28-year-old male patient who underwent spine surgery for cervicodorsal spine injury and experienced sudden, painless vision loss in his left eye following the surgery. On examination, his right eye had a bedside vision of >3/60, while his left eye could only perceive light. The patient's left eye showed mild axial proptosis, supraorbital edema, conjunctival congestion, chemosis, relative afferent papillary defect, and restricted eye movements in all gazes. Fundus examination of the left eye showed pale retina, optic disc pallor, severely attenuated retinal vessels, and an absent cherry red spot suggesting ophthalmic artery occlusion. The right eye anterior segment and fundus findings were normal. Magnetic resonance imaging of the brain and orbit showed mild preseptal thickening in the left orbit, and magnetic resonance venography was normal. This case report is noteworthy in that an ophthalmic artery occlusion has been identified as the cause of sudden, unilateral, painless vision loss associated with ophthalmoplegia subsequent to a spinal surgical procedure.

Correlation of needle biopsy-acquired histopathologic grade of hepatocellular carcinoma with outcomes after thermal ablation.

PURPOSE: To correlate pre-ablation needle biopsy-acquired histopathologic grade of LI-RADS 5 HCC to post-ablation local tumor control rate, intrahepatic distant tumor progression-free survival, and overall survival. MATERIALS AND METHODS: This single-center, retrospective cohort study included adult patients with LI-RADS 5 HCC who received a pre-ablation core needle biopsy within 3 months prior to thermal ablation from January 2015 to December 2022. Histopathologic grade from the needle biopsy was evaluated as predictor of local tumor control rate, intrahepatic distant tumor progression-free survival and overall survival. Kaplan-Meier survival curves were compared using the Gehan-Generalized Wilcoxon test. RESULTS: The study group comprised of 133 patients (mean age, 67 +/- 10 years [SD]; 107 men) with LI-RADS 5 confirmed HCC, stratified into n=18 poorly-differentiated tumors (median follow-up 27.7 months [IQR, 15.5-55.4]) and n=115 well/moderately-differentiated tumors (median follow-up 29.2 months [IQR, 15.4-59.9]). No difference in local tumor control rate was noted between the two cohorts (HR: 1.16 [95% CI: 0.32-4.23]; p=0.898). There was significantly lower intrahepatic distant tumor progression-free survival after thermal ablation in the poorly-differentiated cohort (HR: 2.54 [0.92-7.05]; p<0.001). The overall survival in the poorly-differentiated cohort was also lower, although this did not reach statistical significance (HR: 1.77 [95% CI: 0.60-5.26]; p=0.202). CONCLUSION: Patients with needle-biopsy proven poorly-differentiated LI-RADS 5 HCC have significantly lower intrahepatic distant tumor progression-free survival after thermal ablation compared to well/moderately-differentiated HCC.

Evaluation of Cytotoxic and Anti-cancer Potential of Capsaicin on Lung Cancer Cell Line: An In Vitro Investigation.

Background The leading cause of cancer-related deaths worldwide is lung cancer. Approximately 1.8 million new cases were diagnosed, and 1.6 million individuals died. Available treatment options are inefficient leading to tumour recurrence. Hence there is a need for novel therapeutic advancements in lung cancer treatment. Capsaicin, a naturally occurring protoalkaloid, was found to possess several potential benefits. Aim The aim of the study was to examine capsaicin's cytotoxic and anti-cancer effects in the lung cancer cell line (A549). Materials and methods The cell viability of lung cancer cells treated with capsaicin was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. A549 cells were treated with capsaicin at concentrations ranging from 25 to 150 µM/mL for 24 hours. Changes in cell morphology were observed using a phase-contrast microscope. Nuclear morphological alterations in the lung cancer cells were examined through acridine orange/ethidium bromide (AO/EtBr) staining and viewed under a fluorescent microscope to identify apoptotic nuclei. Gene expression analysis was performed using quantitative real-time PCR (Polymerase Chain Reaction) to evaluate the expression of apoptotic genes, transforming growth factor-beta (TGF-ß), and suppressor of mothers against decapentaplegic 2 (SMAD2). Capsaicin's anti-migratory properties were assessed using a scratch wound healing assay. Result Our study demonstrated that treating lung cancer cells with capsaicin dramatically decreased their vitality, with a statistically significant difference (p<0.05) between the treatment and control groups. In lung cancer cells, we measured the inhibitory concentration (IC-50) at 101.2µM/ml. Following treatment, the number of cells decreased, and those that remained exhibited cytoplasmic membrane blebbing and shrunk. With AO/EtBr staining, treated cells showed an increased number of apoptotic cells. The study's findings showed that after receiving capsaicin, there was a significant downregulation of TGF-ß and SMAD2. Moreover, when compared to control cells, capsaicin-treated cells' migration was markedly reduced. Through modification of the TGF-ß/SMAD2 signaling system, capsaicin therapy dramatically promotes apoptosis and inhibits migration. Conclusion In conclusion, the study's results indicate that capsaicin may have anti-tumor effects on lung cancer cells. To fully comprehend the mechanism underlying capsaicin's anticancer potential and its therapeutic application, further studies are much needed.

Characterization of Microwave Generator Energy and Ablation Volumes following Transarterial Embolization in an In Vivo Porcine Liver Model.

PURPOSE: To characterize the relationship between ablation zone volume (AZV) and microwave ablation (MWA) energy in an in vivo porcine liver model following arterial embolization. MATERIALS AND METHODS: With Institutional Animal Care and Use Committee (IACUC) approval, 11 female swine underwent either right (n = 5) or left (n = 6) hepatic artery embolization under fluoroscopic guidance. Subsequently, ultrasound (US)-guided MWA was performed in each liver segment (left lateral, left medial, right medial, and right lateral) at either 30 W (n = 4 lobes), 60 W (n = 4), 65 W (n = 20), 90 W (n = 8), 120 W (n = 4), or 140 W (n = 4) continuously for 5 minutes. Postprocedural volumetric segmentation was performed on standardized multiphase T1 magnetic resonance (MR) imaging sequences. RESULTS: Mean AZVs in embolized lobes (15.8 mL ± SD 10.6) were significantly larger than those in nonembolized lobes (11.2 mL ± SD 6.5, P < .01). MWA energy demonstrated significant positive linear correlation with both embolized (R2 = 0.66, P < .01) and nonembolized (R2 = 0.64, P < .01) lobes. The slope of the linear models corresponded to a 0.95 mL/kJ (SD ± 0.16) and 0.54 mL/kJ (SD ± 0.09) increase in ablation volume per applied kilojoule of energy (E) in embolized and nonembolized lobes, respectively. In the multivariate model, embolization status significantly modified the relationship between E and AZV as described by the following interaction term: 0.42∗E∗(embolization status) (P = .031). CONCLUSIONS: Linear models demonstrated a near 1.8-fold increase in ratio of AZV per unit E, R(AZV:E), when applied to embolized lobes relative to nonembolized lobes. Absolute AZV differences between embolized and nonembolized lobes were greater at higher-power MWA.

Equity Implications of the Affordable Care Act Among People With Past-Year Criminal Legal Interactions.

OBJECTIVE: This study examined whether expansions of Affordable Care Act (ACA) coverage led to changes in insurance coverage and behavioral health treatment use among adults with past-year criminal legal interactions. METHODS: National Survey on Drug Use and Health data and a difference-in-differences design were used to compare changes in insurance coverage and behavioral health treatment use among respondents with a mental or substance use disorder, by past-year criminal legal involvement (N=103,818). RESULTS: Prior to ACA expansions, respondents with past-year criminal legal involvement (vs. without) were less likely to have insurance (61.5% vs. 79.3%) or to receive mental health treatment (34.7% vs. 36.3%). The ACA coverage expansions reduced insurance disparities for people with criminal legal involvement by almost 5 percentage points. No changes in behavioral health treatment use were found. CONCLUSIONS: Future policies that help people with criminal legal involvement get connected to coverage and treatment are warranted to address persistent disparities in coverage and treatment receipt.

Sexual Orientation, Mental Illness, and Substance Use Disorders Among Criminal Legal System-Involved Individuals.

OBJECTIVE: The purpose of this study was to examine the prevalence of mental illness, substance use disorders, and access to treatment among individuals from sexual minority groups who have been involved with the criminal legal system. METHODS: This study used data from 195,239 heterosexual adults and 14,995 sexual minority adults ages ≥18 years surveyed in the 2015-2019 National Survey on Drug Use and Health. The authors compared mental illness, substance use disorders, and access to treatment between sexual minority and heterosexual adults by using multivariable logistic regression models and controlling for sociodemographic characteristics. RESULTS: Approximately 9% of legal system-involved adults identified as belonging to a sexual minority group. Among legally involved individuals, sexual minority individuals were more likely than heterosexual individuals to have a serious mental illness, suicidal ideation, or depressive thoughts and to use inhalants, hallucinogens, alcohol, marijuana, or cocaine. Legally involved sexual minority individuals were also more likely than their heterosexual counterparts to receive treatment for mental illness or substance use disorders. The increased probability of receiving treatment for mental illness and substance use among sexual minority individuals was also observed when comparing sexual minority and heterosexual adults not involved with the criminal legal system. CONCLUSIONS: This study adds new population-based research to a limited body of evidence on the health disparities and mental health needs of legally involved sexual minority populations. More research and programmatic and policy interventions are needed to better support legally involved sexual minority groups in order to achieve mental health equity for this vulnerable population.

Silencing Transglutaminase Genes TGase2 and TGase3 Has Infection-Dependent Effects on the Heart Rate of the Mosquito Anopheles gambiae.

Transglutaminases are pleiotropic enzymes that in mosquitoes participate in the formation of the mating plug and the wound-induced antimalarial response. Moreover, one transglutaminase, TGase3, negatively regulates the infection-induced aggregation of hemocytes on the heart. Given that TGase3 is an inhibitor of periostial hemocyte aggregation, we used RNAi-based gene silencing followed by intravital video imaging to scrutinize whether any of the three transglutaminases encoded in the genome of the mosquito, Anopheles gambiae, play a role in modulating the heart rate of uninfected and infected mosquitoes. Initially, we confirmed that an infection decreases the heart rate. Then, we uncovered that silencing TGase1 does not impact heart physiology, but silencing TGase2 results in a constant heart rate regardless of infection status, eliminating the infection-induced decrease in the heart rate. Finally, silencing TGase3 decreases the heart rate in uninfected mosquitoes but increases the heart rate in infected mosquitoes. We conclude that TGase2 and TGase3 modulate heart physiology and demonstrate that factors not classically associated with insect circulatory physiology are involved in the functional integration of the immune and circulatory systems of mosquitoes.

Transglutaminase 3 negatively regulates immune responses on the heart of the mosquito, Anopheles gambiae.

The immune and circulatory systems of insects are functionally integrated. Following infection, immune cells called hemocytes aggregate around the ostia (valves) of the heart. An earlier RNA sequencing project in the African malaria mosquito, Anopheles gambiae, revealed that the heart-associated hemocytes, called periostial hemocytes, express transglutaminases more highly than hemocytes elsewhere in the body. Here, we further queried the expression of these transglutaminase genes and examined whether they play a role in heart-associated immune responses. We found that, in the whole body, injury upregulates the expression of TGase2, whereas infection upregulates TGase1, TGase2 and TGase3. RNAi-based knockdown of TGase1 and TGase2 did not alter periostial hemocyte aggregation, but knockdown of TGase3 increased the number of periostial hemocytes during the early stages of infection and the sequestration of melanin by periostial hemocytes during the later stages of infection. In uninfected mosquitoes, knockdown of TGase3 also slightly reduced the number of sessile hemocytes outside of the periostial regions. Taken altogether, these data show that TGase3 negatively regulates periostial hemocyte aggregation, and we hypothesize that this occurs by negatively regulating the immune deficiency pathway and by altering hemocyte adhesion. In conclusion, TGase3 is involved in the functional integration between the immune and circulatory systems of mosquitoes.

Predictive Accuracy of a Polygenic Risk Score for Postoperative Atrial Fibrillation After Cardiac Surgery.

BACKGROUND: Postoperative atrial fibrillation (PoAF) remains a significant risk factor for increased morbidity and mortality after cardiac surgery. The ability to accurately identify patients at risk through clinical risk factors is limited. There is growing evidence that polygenic risk contributes significantly to PoAF and incorporating measures of genetic risk could enhance prediction. METHODS: A retrospective cohort study of 1047 patients of White European ancestry who underwent either coronary artery bypass grafting or valve surgery at a tertiary academic center and were free from a history or persistent preoperative atrial fibrillation. The primary outcome was defined as PoAF based on postoperative ECG reports, medical record documentation, and changes in medication. The exposure was a polygenic risk score (PRS) comprising 2746 single-nucleotide polymorphisms previously associated with atrial fibrillation risk. The prediction of PoAF risk was assessed using measures of model discrimination, calibration, and net reclassification improvement. RESULTS: A total of 259 patients (24.7%) developed PoAF. The PRS was significantly associated with a higher risk for PoAF (odds ratio, 1.63 per SD increase in PRS [95% CI, 1.41-1.90]). Addition of PRS to patient- and procedure-related predictors of PoAF significantly increased the C statistic from 0.742 to 0.782 (change in C statistic, 0.040 [95% CI, 0.021-0.060]) while maintaining good calibration. The addition of the PRS to patient- and procedure-related predictors of PoAF improved model fit (likelihood ratio test, P=2.8×10-15) and significantly improved measures of reclassification (net reclassification improvement, 0.158 [95% CI, 0.066-0.274]). CONCLUSIONS: The PRS for PoAF was associated with improved discrimination, calibration, and risk reclassification compared with conventional clinical predictors suggesting that a PoAF PRS may enhance risk prediction of PoAF in patients undergoing coronary artery bypass grafting or valve surgery.

Digital health developments and drawbacks: a review and analysis of top-returned apps for bipolar disorder.

BACKGROUND: Although a growing body of literature highlights the potential benefit of smartphone-based mobile apps to aid in self-management and treatment of bipolar disorder, it is unclear whether such evidence-based apps are readily available and accessible to a user of the app store. RESULTS: Using our systematic framework for the evaluation of mental health apps, we analyzed the accessibility, privacy, clinical foundation, features, and interoperability of the top-returned 100 apps for bipolar disorder. Only 56% of the apps mentioned bipolar disorder specifically in their title, description, or content. Only one app's efficacy was supported in a peer-reviewed study, and 32 apps lacked privacy policies. The most common features provided were mood tracking, journaling, and psychoeducation. CONCLUSIONS: Our analysis reveals substantial limitations in the current digital environment for individuals seeking an evidence-based, clinically usable app for bipolar disorder. Although there have been academic advances in development of digital interventions for bipolar disorder, this work has yet to be translated to the publicly available app marketplace. This unmet need of digital mood management underscores the need for a comprehensive evaluation system of mental health apps, which we have endeavored to provide through our framework and accompanying database (apps.digitalpsych.org).

Mean platelet volume and cardiac-surgery-associated acute kidney injury: a retrospective study.

PURPOSE: Increased mean platelet volume (MPV) may indicate platelet activation, platelet aggregation, and a resulting prothrombotic state. Such changes in the postoperative period have been associated with organ injury and adverse outcomes. We hypothesized that changes in MPV after cardiac surgery are associated with both a higher risk of acute kidney injury (AKI) and mortality. METHODS: In this retrospective study, we evaluated consecutive patients undergoing adult cardiac surgery patients between 12 December 2011 and 5 June 2018. The change in MPV was derived by calculating the difference between the baseline MPV before surgery and the average postoperative MPV just prior to the occurrence of AKI. We defined postoperative AKI according to Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for Acute Kidney Injury as either a ≥ 50% increase in serum creatinine in the first ten postoperative days, or an increase of ≥ 0.3 mg·dL-1 during any 48-hr window across the ten-day postoperative period. Multivariable logistic regression analysis was used to examine the association between MPV change and postoperative AKI and mortality. RESULTS: Of the 4,204 patients studied, 1,373 (32.7%) developed postoperative AKI, including 83 (2.0%) and 38 (0.9%) who developed stages II and III AKI, respectively. Compared with patients who had an increase in median postoperative MPV of 0.2 femtolitre (fL), those with an increase of 0.8 fL had an 80% increase in the odds of developing AKI (adjusted odds ratio [aOR], 1.80; 95% confidence interval [CI],1.36 to 2.38; P < 0.001) and were almost twice as likely to progress to a higher severity AKI (aOR, 1.66; 95% CI, 1.28 to 2.16; P < 0.001). Change in MPV was not associated with mortality (aOR,1.32; 95% CI, 0.92 to 1.89; P = 0.14). CONCLUSION: Increased MPV change in the postoperative period was associated with both increased risk and severity of AKI, but not mortality.

RéSUMé: OBJECTIF: Un volume plaquettaire moyen (VPM) augmenté peut être indicatif d'une activation plaquettaire, d'une agrégation plaquettaire, et de l'état prothrombotique qui en résulte. De tels changements en période postopératoire ont été associés à des lésions aux organes et à des devenirs défavorables. Nous avons émis l'hypothèse que des changements du VPM après une chirurgie cardiaque seraient associés à un risque plus élevé d'insuffisance rénale aiguë et de mortalité. MéTHODE: Dans cette étude rétrospective, nous avons évalué des patients adultes consécutifs subissant une chirurgie cardiaque entre le 12 décembre 2011 et le 5 juin 2018. Le changement de VPM a été dérivé en calculant la différence entre le VPM de base avant la chirurgie et le VPM postopératoire moyen juste avant la survenue de l'IRA. Nous avons défini une IRA postopératoire sur la base des Directives Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for Acute Kidney Injury (Les maladies rénales: Guide d'exercice clinique pour améliorer les devenirs globaux pour l'insuffisance rénale aiguë) en tant qu'une augmentation ≥ 50 % de la créatine sérique au cours des dix premiers jours postopératoires, ou une augmentation de ≥ 0,3 mg·dL−1 pendant toute fenêtre de 48 h au cours des dix premiers jours postopératoires. Une analyse multivariée de régression logistique a été utilisée pour examiner l'association entre le changement de VPM et l'IRA postopératoire et la mortalité. RéSULTATS: Parmi les 4204 patients à l'étude, 1373 (32,7 %) ont souffert d'IRA postopératoire, y compris 83 (2,0 %) et 38 (0,9 %) qui ont développé des IRA de stade II et III, respectivement. Par rapport aux patients ayant manifesté une augmentation du VPM postopératoire médian de 0,2 femtolitre (fL), ceux affichant une augmentation de 0,8 fL ont démontré une augmentation de 80 % de la probabilité d'IRA (rapport de cotes ajusté [RCA], 1,80; intervalle de confiance [IC] 95 %, 1,36 à 2,38; P < 0,001) et couraient un risque pratiquement deux fois plus élevé de voir leur IRA progresser à un stade plus grave (RCA, 1,66; IC 95 %, 1,28 à 2,16; P < 0,001). Les changements de VPM n'étaient pas associés à la mortalité (RCA, 1,32; IC 95 %, 0,92 à 1,89; P = 0,14). CONCLUSION: Une augmentation accrue du VPM en période postopératoire a été associée à un risque et une gravité accrus d'IRA, mais pas à la mortalité.