Anatomical Factors Affecting the Complexity of Maxillary Sinus Augmentation in Saudi Patients: A Cone Beam Computed Tomography (CBCT) Study.

AIM: This study aims to evaluate the anatomical variations of the maxillary sinus and determine the difficulty score of maxillary sinus augmentation (MSA) in Saudi patients seeking dental implant rehabilitation of the posterior maxilla using cone beam computed tomography (CBCT). METHODOLOGY: CBCT records of dental patients seeking treatment at a University Dental Teaching Hospital between 2019 and 2023 were retrospectively analyzed. Measurements were obtained from CBCT images, including membrane thickness, sinus width, buccal bone thickness, presence of maxillary sinus septa, residual alveolar ridge height, angle of the buccolingual sinus wall, and the presence of the alveolar antral artery (AAA). The difficulty score for MSA was determined based on these anatomical factors. RESULTS: A total of 107 maxillary sinuses in 86 subjects were evaluated. The average membrane thickness was 2.23 mm, with males showing significantly higher thickness than females. Sinus septa were found in 54 (50.5%) sinuses, with 18 (17%) of sinuses having interfering septa. Twenty-three (21.5%) sinuses had a residual alveolar ridge height of less than 4 mm. The average angle of the buccolingual sinus wall was 79.39°, indicating a high prevalence of wide-shaped sinuses. The average sinus width was 14.09 mm, with 55 sinuses (51.4%) less than 15 mm. The average buccal bone thickness was 1.07 mm, in 29 (27%) sinuses, the thickness was more than 2 mm. AAA was visualized in 60 (56%) of sinuses, with 45 (42%) of sinuses having AAA interfering with the MSA window. CONCLUSIONS: In this study, most sinuses were classified as simple or moderate difficulty, with higher membrane thickness, presence of septa, and AAA being the significant risk factors for complications. These findings provide valuable insights for implant surgeons in Saudi patients seeking dental implant rehabilitation of the posterior maxilla, enabling them to anticipate and minimize potential complications during MSA procedures.

Structure of TnsABCD transpososome reveals mechanisms of targeted DNA transposition.

Tn7-like transposons are characterized by their ability to insert specifically into host chromosomes. Recognition of the attachment (att) site by TnsD recruits the TnsABC proteins to form the transpososome and facilitate transposition. Although this pathway is well established, atomic-level structural insights of this process remain largely elusive. Here, we present the cryo-electron microscopy (cryo-EM) structures of the TnsC-TnsD-att DNA complex and the TnsABCD transpososome from the Tn7-like transposon in Peltigera membranacea cyanobiont 210A, a type I-B CRISPR-associated transposon. Our structures reveal a striking bending of the att DNA, featured by the intercalation of an arginine side chain of TnsD into a CC/GG dinucleotide step. The TnsABCD transpososome structure reveals TnsA-TnsB interactions and demonstrates that TnsC not only recruits TnsAB but also directly participates in the transpososome assembly. These findings provide mechanistic insights into targeted DNA insertion by Tn7-like transposons, with implications for improving the precision and efficiency of their genome-editing applications.

Embolization of a type 2 endoleak using a micropuncture introducer set and a triple-coaxial system through the deep iliac circumflex artery via the ipsilateral femoral artery.

An 83-year-old man underwent embolization for a type 2 endoleak following endovascular aortic repair for an abdominal aortic aneurysm. The type 2 endoleak originated from the left iliac circumflex artery, which was located very close to the puncture site in the left femoral artery. This proximity made the embolization procedure challenging; however, by employing a combination of a micropuncture introducer set and a triple-coaxial system, embolization with N-butyl-2-cyanoacrylate was successfully achieved.

How the double-ring ClpAP protease motor grips the substrate to unfold and degrade stable proteins.

Loops in the axial channels of ClpAP and other AAA+ proteases bind a short peptide degron connected by a linker to the N- or C-terminal residue of a native protein to initiate degradation. ATP hydrolysis then powers pore-loop movements that translocate these segments through the channel until a native domain is pulled against the narrow channel entrance, creating an unfolding force. Substrate unfolding is thought to depend on strong contacts between pore loops and a subset of amino acids in the unstructured sequence directly preceding the folded domain. Here, we identify such contact sequences that promote grip for ClpAP and use ClpA structures to place these sequences within ClpA's two AAA+ rings. The positions and chemical nature of certain residues within an unstructured segment that are positioned to interact with the D2 ring have major positive effects on substrate unfolding, whereas segments located within the D1 ring have little consequence. Within the D2-bound segment, two short elements are critical for accelerating degradation; one is at the 'top' of D2 and consists of at least two properly positioned non-slippery residues. In contrast, the second D2 element, which can be as short as one residue, is positioned to contact pore loops near the 'bottom' of this ring. Comparison with similar studies for ClpXP reveals that positioning a well-gripped substrate sequence within the major unfoldase motor is more important than its proximity to the folded domain and that charged, polar, and hydrophobic residues all contribute favorable contacts to substrate grip.

Examining the relationship between parents' self-reported mindfulness and observed language use in attachment-relevant communication.

Parents' language use is an important context for early socialization. We examined the relationship between parents' self-reported mindfulness and observed language use in two forms of attachment-relevant communication. Sixty-three parents of 6-18-month-old infants from Australia (n = 32) and New Zealand (n = 31) completed the five facets of mindfulness-short form (FFMQ-SF) questionnaire, the adult attachment interview (AAI), and a 10-min play session with their infant. We examined parents' frequency of word usage within the categories of the linguistic inquiry word count (LIWC) text analysis program to explore the relationship between mindfulness and language use. Mindfulness was associated with cognitive, affective, perceptual, and time orientation language use in the AAI. However, fewer associations were identified between mindfulness and language use in the parent-infant play session. Results are discussed in terms of their relevance to mindfulness and attachment.

El uso del lenguaje por parte de los padres es un contexto importante para la temprana socialización. Examinamos la relación entre la auto reportada atención consciente de los padres y el observado uso del lenguaje en dos formas de comunicación relevantes a la unión afectiva. Sesenta y tres progenitores de infantes entre 6 y 18 meses de edad de Australia (n = 32) y Nueva Zelanda (n = 31) completaron el cuestionario de Cinco Facetas de la Atención Consciente en su formato corto (FFMQ­SF), la Entrevista de la Afectividad Adulta (AAI), así como una sesión de juego de diez minutos con sus infantes. Examinamos la frecuencia del uso de palabras por parte de los padres dentro de las categorías del programa de análisis de texto Investigación Lingüística del Conteo de Palabras (LIWC) para explorar la relación entre la atención consciente y el uso del lenguaje. Se asoció la atención consciente con el uso del lenguaje cognitivo, afectivo, perceptivo y con orientación del tiempo de la AAI. Sin embargo, menos asociaciones se identificaron entre la atención consciente y el uso del lenguaje en la sesión de juego entre progenitor e infante. Los resultados se discuten en términos de su relevancia para la atención consciente y la afectividad.

Sec18 side-loading is essential for universal SNARE recycling across cellular contexts.

SNARE proteins drive membrane fusion as their core domains zipper into a parallel four-helix bundle1,2. After fusion, these bundles are disassembled by the AAA+ protein Sec18/NSF and its adaptor Sec17/ α-SNAP3,4 to make them available for subsequent rounds of membrane fusion. SNARE domains are often flanked by C-terminal transmembrane or N-terminal domains5. Previous structures of the NSF-α-SNAP-SNARE complex revealed SNARE domain threaded through the D1 ATPase ring6, posing a topological constraint as SNARE transmembrane domains would prevent complete substrate threading as suggested for other AAA+ systems7. Here, in vivo mass-spectrometry reveals N-terminal SNARE domain interactions with Sec18, exacerbating this topological issue. Cryo-EM structures of a yeast SNARE complex, Sec18, and Sec17 in a non-hydrolyzing condition shows SNARE Sso1 threaded through the D1 and D2 ATPase rings of Sec18, with its folded, N-terminal Habc domain interacting with the D2 ring. This domain does not unfold during Sec18/NSF activity. Cryo-EM structures under hydrolyzing conditions revealed substrate-released and substrate-free states of Sec18 with a coordinated opening in the side of the ATPase rings. Thus, Sec18/NSF operates by substrate side-loading and unloading topologically constrained SNARE substrates.

Endoplasmic reticulum stress in abdominal aortic aneurysm.

Abdominal aortic aneurysms (AAAs) are characterized by permanent dilatation of the abdominal aorta, which is accompanied by inflammation, degradation of the extracellular matrix (ECM) and disruption of vascular smooth muscle cell (VSMC) homeostasis. Endoplasmic reticulum (ER) stress is involved in the regulation of inflammation, oxidative stress and VSMC apoptosis, all of which are critical factors in AAA development. Although several studies have revealed the occurrence of ER stress in AAA development, the specific biological functions of ER stress in AAA development remain largely unknown. Given that targeting ER stress is a promising strategy for treating AAAs, further investigation of the physiological and pathological roles of ER stress in AAA development is warranted.

Feasibility of contrast-enhanced ultrasound in the detection and classification of endoleaks after endovascular aneurysm repair.

Background: Endoleaks are common complications after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). Computed tomographic angiography (CTA)/digital subtraction angiography (DSA) is considered the gold standard for evaluating contrast-enhanced ultrasound (CEUS) accuracy in the detection and classification of endoleaks. In recent years, CEUS has been widely used in this field. This study aimed to analyze the accuracy of CEUS in the detection and classification of endoleaks after EVAR. Methods: The data of 98 patients who underwent abdominal aorta CEUS from November 2017 to September 2023 in the ultrasound (US) department of Beijing Hospital were retrospectively analyzed. All the patients underwent EVAR of AAA before CEUS and CTA/DSA, and had complete clinical data. The CEUS and CTA/DSA results were compared to detect endoleaks and categorize the specific types of endoleaks. Results: Among the 98 patients, 74 were male and 24 were female. The patients had an average age of 74.8±9.8 years (range, 43-90 years). Among the 98 patients, 37 (37.8%) endoleaks were detected by CEUS, of which 8 were type Ia, 2 were type Ib, 15 were type II, 7 were type III, 2 were type IV, 2 were type Ia combined with type III, and 1 was type II combined with type III. In addition, among these 98 patients, 39 (39.8%) endoleaks were detected by CTA/DSA, of which 8 were type Ia, 3 were type Ib, 18 were type II, 6 were type III, 2 were type Ia combined with type III, 1 was type II combined with type III, and 1 was type Ib combined with type II. The sensitivity and specificity of CEUS in the detection of endoleaks were 92.3% and 98.3%, respectively. CEUS and CTA/DSA had similar diagnostic efficacy and good consistency in the detection and classification of endoleaks (Kappa value: 0.914, P<0.01). Conclusions: CEUS has high sensitivity and specificity in the detection and classification of endoleaks following EVAR, and its diagnostic efficacy is similar to that of CTA/DSA. In addition, US is safe, non-invasive and repeatable, and thus is worthy of extensive clinical application.

Unravelling the anti-apoptotic role of Plasmodium falciparum Prohibitin-2 (PfPhb2) in maintaining mitochondrial homeostasis.

The functional mitochondrion is vital for the propagation of the malaria parasite in the human host. Members of the SPFH protein family, Prohibitins (PHBs), are known to play crucial roles in maintaining mitochondrial homeostasis and cellular functions. Here, we have functionally characterized the homologue of the Plasmodium falciparumProhibitin-2 (PfPhb2) protein. A transgenic parasite line, generated using the selection-linked integration (SLI) strategy for C-terminal tagging, was utilized for cellular localization as well as for inducible knock-down of PfPhb2. We show that PfPhb2 localizes in the parasite mitochondrion during the asexual life cycle. Inducible knock-down of PfPhb2 by GlmS ribozyme caused no significant effect on the growth and multiplication of parasites. However, depletion of PfPhb2 under mitochondrial-specific stress conditions, induced by inhibiting the essential mitochondrial AAA-protease, ClpQ protease, results in enhanced inhibition of parasite growth, mitochondrial ROS production, mitochondrial membrane potential loss and led to mitochondrial fission/fragmentation, ultimately culminating in apoptosis-like cell-death. Further, PfPhb2 depletion renders the parasites more susceptible to mitochondrial targeting drug proguanil. These data suggest the functional involvement of PfPhb2 along with ClpQ protease in stabilization of various mitochondrial proteins to maintain mitochondrial homeostasis and functioning. Overall, we show that PfPhb2 has an anti-apoptotic role in maintaining mitochondrial homeostasis in the parasite.

Association of serum vitamin D with diagnosis and growth of abdominal aortic aneurysm.

Objective: We examined the associations between 25-hydroxy vitamin D (25(OH)D3) concentration and the diagnosis and growth of abdominal aortic aneurysm (AAA). Methods: AAA cases and healthy controls were recruited from vascular centers or the community. A subset of participants with AAA were monitored by repeat ultrasound examination to assess AAA growth. Serum 25(OH)D3 concentration was measured using a validated mass spectrometry method and categorized into guideline-recommended cut-points after deseasonalization. The associations between deseasonalized 25(OH)D3 concentration and AAA diagnosis and growth were examined using logistic regression and linear mixed effects modeling. Results: A total of 4673 participants consisting of 873 (455 controls and 418 cases) from Queensland and 3800 (3588 controls and 212 cases) from Western Australia were recruited. For every 1 standard deviation increase in 25(OH)D3 concentration, odds of AAA diagnosis was significantly reduced in both Queensland (adjusted odds ratio: 0.81; 95% confidence interval [CI]: 0.69-0.95; P = .009) and Western Australia (adjusted odds ratio: 0.80; 95% CI: 0.68-0.94; P = .005) cohorts. A subset of 310 eligible participants with small AAA from both regions were followed for a median of 4.2 (interquartile range: 2.0-5.8) years. Compared with vitamin D sufficient participants (50 to ˂75 nmol/L), annual mean AAA growth was significantly greater in those with higher vitamin D (≥75 nmol/L) (adjusted mean difference: 0.1 mm/y, 95% CI: 0.1-0.2; P < .001). Conclusions: High 25(OH)D3 concentration was paradoxically associated with a lower likelihood of AAA diagnosis and faster AAA growth. Further research is needed to resolve these conflicting findings.

Enhancing clinical outcomes: Point of care ultrasound in the precision diagnosis and Management of Abdominal Aortic Aneurysms in emergency medicine: A systematic review and meta-analysis.

This meta-analysis evaluates the efficacy of point-of-care ultrasound (POCUS) in diagnosing abdominal aortic aneurysm (AAA) in the emergency department (ED). A systematic search of PubMed, Cochrane Library, Scopus, and Google Scholar identified studies published until July 2024. Nine studies were included, revealing that POCUS is highly accurate in diagnosing AAA, with a pooled sensitivity of 98.33% and specificity of 99.84%. Additionally, data from three studies indicated that 24.5% of patients with positive AAA scans were diagnosed with ruptured AAAs. The results suggest that emergency physicians can accurately detect and manage AAA using POCUS, even with limited training.

Simultaneous Percutaneous Coronary Intervention (PCI) and Endovascular Aneurysm Repair (EVAR): A Preliminary Report.

Background: Performing percutaneous coronary intervention (PCI) and endovascular aneurysm repair (EVAR) at the same time represents a groundbreaking development in the multidisciplinary treatment of cardiovascular disease. This combined PCI-EVAR approach bridges a critical gap by offering treatment for patients who have both coronary artery disease and aortic aneurysms. This innovative strategy exemplifies the evolving landscape of cardiovascular care, providing a new solution for complex clinical situations that previously required separate procedures. Methods: Six patients with critical coronary artery lesions and asymptomatic infrarenal aortic aneurysms (AAAs) ≥ 6 cm diameter, as well as one patient with critical coronary artery lesions and endoleak type 1A with aneurysms ≥ 6 cm, underwent simultaneous coronary artery revascularization through percutaneous intervention (PCI) and endovascular aneurysm repair (EVAR). The occurrence of any intraoperative or postoperative complication was considered to be the primary endpoint of the study, including the abortion or failure of either PCI or EVAR, bleeding requiring a conversion to open surgical procedures, the failure of local anesthesia, postoperative myocardial or lower limb ischemia, and a postoperative serum creatinine level of >125 mmol/L or of >180 mmol/L in patients affected by chronic renal failure. The overall length of the procedure, X-ray exposure, the quantity of iodine contrast medium administered, and the length of recovery were considered to be secondary endpoints. Results: Postoperative complications included two episodes of acute renal failure in the two patients already affected by chronic renal failure, which were easily resolved with adequate daily hydration and the elimination of nephrotoxic drugs. In no cases did cardiac ischemia or lower limb ischemia occur. The average procedure duration was 198 min (range: 180-240 min), the average fluoroscopy duration was 41.7 min (range: 35-50 min), the average amount of iodinated contrast medium was 34.8 mL (range: 30-40 mL), and the mean length of hospitalization was 2.7 days (range: 2-5 days). Conclusions: In selected patients, this surgical approach has demonstrated safety, reduced hospitalization times, minimized risks associated with complications from the untreated condition if procedures were performed at different times, and facilitated the effective management of intraoperative complications due to the presence of a multidisciplinary team. However, the limited number of patients necessitates further research.

High proportion of undiagnosed diabetes in patients surgically treated for infrarenal abdominal aortic aneurysm: findings from the multicentre Norwegian Aortic Aneurysm and Diabetes (ABANDIA) Study.

BACKGROUND: The aim was to investigate the total prevalence of known and undiagnosed diabetes mellitus (DM), and the association of DM with perioperative complications following elective, infrarenal, open surgical (OSR) or endovascular (EVAR), Abdominal Aortic Aneurysm (AAA) repair. METHODS: In this Norwegian prospective multicentre study, 877 patients underwent preoperative screening for DM by HbA1c measurements from November 2017 to December 2020. Diabetes was defined as screening detected HbA1c ≥ 48 mmol/mol (6.5%) or previously diagnosed diabetes. The association of DM with in-hospital complications, length of stay, and 30-day mortality rate were evaluated using adjusted and unadjusted logistic regression models. RESULTS: The total prevalence of DM was 15% (95% CI 13%,17%), of which 25% of the DM cases (95% CI 18%,33%) were undiagnosed upon admission for AAA surgery. The OSR to EVAR ratio was 52% versus 48%, with similar distribution among DM patients, and no differences in the prevalence of known and undiagnosed DM in the EVAR versus the OSR group. Total 30-day mortality rate was 0.6% (5/877). Sixty-six organ-related complications occurred in 58 (7%) of the patients. DM was not statistically significantly associated with a higher risk of in-hospital organ-related complications (OR 1.23, 95% CI 0.57,2.39, p = 0.57), procedure-related complications (OR 1.48, 95% CI 0.79,2.63, p = 0.20), 30-day mortality (p = 0.09) or length of stay (HR 1.06, 95% CI 0.88,1.28, p = 0.54). According to post-hoc-analyses, organ-related complications were more frequent in patients with newly diagnosed DM (n = 32) than in non-DM patients (OR 4.92; 95% CI 1.53,14.3, p = 0.005). CONCLUSION: Twenty-five percent of all DM cases were undiagnosed at the time of AAA surgery. Based on post-hoc analyses, undiagnosed DM seems to be associated with an increased risk of organ related complications following AAA surgery. This study suggests universal DM screening in AAA patients to reduce the number of DM patients being undiagnosed and to improve proactive diabetes care in this population. The results from post-hoc analyses should be confirmed in future studies.

THE ASSOCIATION BETWEEN PLASMA PROINFLAMMATORY CYTOKINE CONCENTRATIONS AND ENDOLEAK AFTER ENDOVASCULAR AORTIC ANEURYSM REPAIR.

BACKGROUND: The most common complication after endovascular aneurysm repair (EVAR) is continuous sac perfusion, known as endoleak. Evaluating markers released from the aneurysm wall into circulation has been suggested as a possible alternative for detecting endoleaks. The aim of this study was to examine whether circulating concentrations of different proinflammatory interleukins (IL-1ß, IL-2, IL-6, IL-8), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-α) were elevated in patients with endoleak after EVAR. METHODS: A prospective observational study with 100 patients undergoing elective EVAR was conducted. Blood samples were taken before surgery, at 7 days, 6 months, and 12 months after EVAR to quantify the mentioned cytokines using a Bio-Plex assay. Patients were followed up for 12 months to detect endoleak occurrence. RESULTS: In patients with endoleak, mean concentrations of certain cytokines in plasma differed significantly from those without endoleak: preoperative IL-8 (9.83; p<0.001), preoperative MCP-1 (75.94; p=0.003), preoperative TNF-α (5.46; p=0.05), among others. A binary logistic regression analysis revealed that preoperative IL-8 (p=0.003), MCP-1 at 7 days postoperative (p = 0.002), and IL-1 at 12 months postoperative were significantly associated with endoleak, with IL-1 being the most influential biomarker (OR=2.2). A ROC curve showed an area under the curve of 0.7, with cutoff points of 33.4 for preoperative IL-8, 145 for MCP-1 at 7 days postoperative, and 2.3 for IL-1 at 12 months postoperative. CONCLUSIONS: This study suggests that inflammatory biomarkers such as IL-1, IL-8, MCP-1, and TNF-α have the potential to serve as important adjuncts to conventional imaging techniques in monitoring patients post-EVAR. These biomarkers may help identify individuals at higher risk of developing endoleaks, guiding more focused and timely imaging follow-up. However, their practical applicability requires further investigation.

The role of dysbiotic gut mycobiota in modulating risk for abdominal aortic aneurysm.

Abdominal aortic aneurysm (AAA) is a large-vessel disease with high mortality, characterized by complex pathogenic mechanisms. Current therapeutic approaches remain insufficient to halt its progression. Fungi are important members of the gut microbiota. However, their characteristic alterations and roles in AAA remain unclear. This study investigated the role of gut fungal communities in the development of AAA through metagenomic sequencing of fecal samples from 31 healthy individuals and 33 AAA patients. We observed significant dysbiosis in the gut mycobiomes of AAA patients compared to healthy individuals, characterized by an increase in pathogenic fungi like Candida species and a decrease in beneficial yeasts such as Saccharomyces cerevisiae. The changes in fungal populations correlated strongly with clinical indicators of AAA, highlighting their potential for diagnosing and predicting AAA progression. Furthermore, our animal experiments demonstrated that Saccharomyces cerevisiae significantly ameliorated pathological alterations in AAA mice, suggesting a protective role for specific yeast strains against AAA development. These findings underscore the significant impact of gut mycobiomes on AAA and suggest that modulating these fungal communities could offer a novel therapeutic approach. Our research advances the understanding of the influence of gut microbiome on vascular diseases and suggests potential non-surgical approaches for managing AAA. By elucidating the diagnostic and therapeutic potential of gut fungi in AAA, this study provided important clues for future clinical strategies and therapeutic developments in the field of vascular medicine. IMPORTANCE: Our research highlights the crucial role of gut fungi in abdominal aortic aneurysm (AAA) development. By analyzing fecal samples from AAA patients and healthy controls, we discovered significant dysbiosis in gut fungal communities, characterized by an increase in harmful Candida species and a decrease in beneficial yeasts like Saccharomyces cerevisiae. This dysbiosis was correlated with the severity of AAA. Importantly, in animal experiments, supplementing with Saccharomyces cerevisiae significantly slowed AAA progression. These findings suggest that modulating gut fungi may offer a novel, non-surgical approach to the diagnosis and treatment of AAA, potentially reducing the need for invasive procedures.

Metformin Improves the Function of Abdominal Aortic Aneurysm Patient Derived Aortic Smooth Muscle Cells.

OBJECTIVE: Type 2 diabetes mellitus (T2DM) is a cardiovascular risk factor. Paradoxically, a decreased risk of abdominal aortic aneurysm (AAA) presence and growth rate is described among patients with T2DM, associated with metformin use. This study aimed to investigate the effect of metformin on AAA patient derived aortic smooth muscle cell (SMC) function. METHODS: Aortic biopsies were obtained from patients with AAA (n = 21) and controls (n = 17) during surgery. The SMCs of non-pathological aortic controls, non-diabetic patients with AAA, and diabetic patients with AAA were cultured from explants and treated with or without metformin. The SMC contractility was measured upon ionomycin stimulation, as well as metabolic activity, proliferation, and migration. Then, mRNA and protein expression of markers for contraction, metabolic activity, proliferation, and inflammation were measured. RESULTS: The mRNA expression of KLF4 and GYS1, genes involved in metabolic activity, differed between the SMCs from non-diabetic and diabetic patients with AAA before metformin stimulation (p < .041). However, the effect of metformin on the various SMC functions was similar between non-diabetic and diabetic patients with AAA. Upon stimulation, metformin increased the contractility of AAA patient SMCs (p = .001). The mRNA expression of smoothelin, a marker for the contractile phenotype, increased in the SMCs of patients with AAA after treatment with metformin (p = .006). An increase in metabolic activity (p < .001) and a decrease in proliferation (p < .001) and migration were found in the SMCs of controls and patients with AAA with metformin. Increased mRNA expression of PPARγ, a nuclear receptor involved in mitochondrial biogenesis (p < .009), and a decrease in gene expression of Ki-67, a marker for proliferation (p < .005), were observed. Gene expression of inflammation markers MCP-1 and IL-6, and protein expression of NF-κB p65 decreased after treatment with metformin in patients with AAA. CONCLUSION: This study found that metformin increases contractility and metabolic activity, and reduces proliferation, migration, and inflammation in aortic SMCs in vitro.

Optimization of a commercial portal dose image prediction algorithm for pre-treatment verifications of plans using unflattened photon beams.

Background: The aim was to improve the portal dosimetry-based quality assurance results of conventional treatment plans by adjusting the multileaf collimator (MLC) dosimetric leaf gap (DLG) and transmission (T) values of the anisotropic analytic algorithm (AAA) used for portal dose image prediction (PDIP). Materials and methods: The AAA-based PDIP v. 16.1 algorithm (PDIP-AAA) of the Eclipse TPS was configured for 6 MV FFF energy. Optimal DLG and T values were achieved for this algorithm by comparing predicted versus measured portal images of the Chair pattern. Twenty clinical plans using 6 MV FFF beams were verified using the optimal PDIP-AAA algorithm and the standard PDIP v. 16 algorithm (PDIP-vE), configured using the van Esch package. The 3% global/2 mm gamma passing rates (GPRs) and average gamma indexes (AGIs) were computed for each acquired image. For each plan, the mean GPR (GPRmean) and mean GAI (GAImean) were compared for both algorithms. A 2-tailed Student t-test (α = 0.05) was used to evaluate whether there was a statistically significant difference. Results: Optimal values of DLG = 0.1 mm and T = 0.01 were found for the PDIP-AAA algorithm, providing significantly better values of GPRmean and AGImean than PDIP-vE (p < 0.001). All plans verified with PIDP-AAA showed GPRmean ≥ 95%. In contrast, only 45% of the plans reported GPRmean ≥ 95% with the PDIP-vE algorithm. Conclusions: The MLC parameters available in the PDIP-AAA model must be tuned to improve the accuracy of the predicted dose image. This work-around is not possible using the standard PDIP algorithm. The adjusted PDIP-AAA resulted in significantly better results than PDIP-vE.

A single amino acid substitution in the AAA-type ATPase LRD6-6 activates immune responses but decreases grain quality in rice.

Plant spotted leaf (spl) mutants are useful to reveal the regulatory mechanisms of immune responses. Thus, in crop plants, their agronomic traits, especially the grain quality are usually ignored. Here, we characterized a rice spl mutant named spl-A (spotted leaf mutant from A814) that shows autoimmunity, broad-spectrum disease resistance and growth deterioration including decreased rice quality. A single nucleotide mutation of C1144T, which leads to change of the 382nd proline to serine, in the gene encoding the ATPases associated with diverse cellular activities (AAA)-type ATPase LRD6-6 is responsible for the phenotype of the spl-A mutant. Mechanistically, this mutation impairs LRD6-6 ATPase activity and disrupts its interaction with endosomal sorting complex required for transport (ESCRT)-III subunits OsSNF7.1/7.2/7.3. And thus, leading to compromise of multivesicular bodies (MVBs)-mediated vesicle trafficking and accumulation of ubiquitinated proteins in both leaves and seeds of spl-A. Therefore, the immune response of spl-A is activated, and the growth and grain quality are deteriorated. Our study identifies a new amino acid residue that important for LRD6-6 and provides new insight into our understanding of how MVBs-mediated vesicle trafficking regulates plant immunity and growth, including grain quality in rice.

Endovascular Aortic Repair With the E-Tegra Device: Preliminary Outcomes From a Multicenter National Registry.

PURPOSE: Endovascular aortic repair (EVAR) is currently expanding its feasibility thanks to design innovations, but hostile proximal necks and narrow iliac arteries are still a constraint, as expressed by the Instructions for Use (IFU) of most devices. Our aim is to report the preliminary results of the E-Tegra endograft in infrarenal abdominal aortic aneurysms (AAAs) performed in 15 high-volume centers. MATERIALS AND METHODS: The e-Tegra Italian endoGraft REgistry (TIGRE) is a prospectively maintained database of consecutive EVAR with the E-Tegra stent-graft across 15 participating centers between March 2021 and March 2023. The registry records baseline clinical data, anatomic measurements of the abdominal aorta, perioperative and postoperative outcomes, with a scheduled follow-up period of 3 years for all patients. This is a preliminary analysis of the first results updated to January 2024. The primary endpoints are technical and clinical success, perioperative mortality, freedom from endograft rupture, and aortic-related mortality. The secondary endpoints are freedom from reintervention, and any type of endoleak (EL). The results were analyzed in relation with the anatomic characteristics of the AAAs, namely, iliac axes tortuosity and proximal neck hostility. RESULTS: The registry included 147 consecutive EVAR (138 elective and 9 in emergent setting), 7 of which were associated with an iliac branch implantation. Ninety patients had at least 1 criterion of anatomical hostility, and 25 were treated outside the device IFU. Primary technical success was achieved in 146 cases (99.3%) and assisted success in 147 (100%), with no perioperative mortality. After a median follow-up period of 20 months, no aneurysm-related mortality occurred. Reinterventions were 5: 2 for type IB EL and 3 for type II ELs with aneurysm sac increase. Five more type II ELs with aneurysm sac stability are under observation. No differences in terms of reinterventions were noted between aneurysms with standard and hostile anatomy. CONCLUSION: The E-Tegra endograft is safe and effective in treating AAAs with standard and hostile anatomy, with a low rate of complications and reinterventions, although longer-term outcomes and larger numbers are needed to compare its performances related to specific anatomic criteria. CLINICAL IMPACT: This multi-center nationwide Registry reports a real-world experience of EVAR performed with the E-Tegra abdominal endograft across 15 high-volume Centers, providing early- and mid-term device-specific results, which will help vascular surgeons in endograft selection. In particular, this study focuses on clinical results obtained in treating aneurysms with hostile anatomy, analyzing the performances of the E-Tegra endograft in cases of hostile proximal necks and narrow or tortuous iliac axes.

Ruptured AAA: bridging the gap between international guidelines and local clinical realities.

BACKGROUND: Treatment of asymptomatic Abdominal Aortic Aneurysms (AAA) presents a clinical challenge, requiring a delicate balance between rupture risk, patient comorbidities, and intervention-related complications. International guidelines recommend intervention for specific AAA size thresholds, but these are based on historical trials with limited female representation. We aimed to analyse disease characteristics, AAA size at rupture, and intervention outcomes in patients with ruptured AAA from 2009 to 2023 to investigate the gap between guidelines and local realities. METHODS: This single-centre retrospective cohort study analysed electronic health records of patients treated for a ruptured AAA, excluding those who were managed palliatively. The study assessed patients' demographics, risk factors, comorbidities, clinical presentation, radiological characteristics, and outcomes. RESULTS: Of 164 patients (41 females, 123 males, median age 73.5), 93.3% presented with abdominal or back pain. The median AAA size at rupture was 8.0 cm in males and 7.6 cm in females. No significant correlations were found between demographic characteristics, risk factors, AAA size, repair modality, and outcomes. Trends show a decline in AAA prevalence and rupture rates, aligning with global health initiatives. Post-intervention survival rates at 30 days were 70.7% (67.5% in males and 80.0% in females), and at 2 years were 65.85% (61.7% in males and 70.0% in females). CONCLUSION: Evolving AAA trends and improved post-intervention survival rates warrant a critical reassessment of existing intervention recommendations. Adjusting intervention thresholds to larger sizes may be justified to optimise the risk-benefit ratio.