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1.
Alzheimers Dement ; 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39031528

ABSTRACT

INTRODUCTION: The apolipoprotein E gene (APOE) is an established central player in the pathogenesis of Alzheimer's disease (AD), with distinct apoE isoforms exerting diverse effects. apoE influences not only amyloid-beta and tau pathologies but also lipid and energy metabolism, neuroinflammation, cerebral vascular health, and sex-dependent disease manifestations. Furthermore, ancestral background may significantly impact the link between APOE and AD, underscoring the need for more inclusive research. METHODS: In 2023, the Alzheimer's Association convened multidisciplinary researchers at the "AAIC Advancements: APOE" conference to discuss various topics, including apoE isoforms and their roles in AD pathogenesis, progress in apoE-targeted therapeutic strategies, updates on disease models and interventions that modulate apoE expression and function. RESULTS: This manuscript presents highlights from the conference and provides an overview of opportunities for further research in the field. DISCUSSION: Understanding apoE's multifaceted roles in AD pathogenesis will help develop targeted interventions for AD and advance the field of AD precision medicine. HIGHLIGHTS: APOE is a central player in the pathogenesis of Alzheimer's disease. APOE exerts a numerous effects throughout the brain on amyloid-beta, tau, and other pathways. The AAIC Advancements: APOE conference encouraged discussions and collaborations on understanding the role of APOE.

2.
HLA ; 103(6): e15543, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38837862

ABSTRACT

The MHC class I region contains crucial genes for the innate and adaptive immune response, playing a key role in susceptibility to many autoimmune and infectious diseases. Genome-wide association studies have identified numerous disease-associated SNPs within this region. However, these associations do not fully capture the immune-biological relevance of specific HLA alleles. HLA imputation techniques may leverage available SNP arrays by predicting allele genotypes based on the linkage disequilibrium between SNPs and specific HLA alleles. Successful imputation requires diverse and large reference panels, especially for admixed populations. This study employed a bioinformatics approach to call SNPs and HLA alleles in multi-ethnic samples from the 1000 genomes (1KG) dataset and admixed individuals from Brazil (SABE), utilising 30X whole-genome sequencing data. Using HIBAG, we created three reference panels: 1KG (n = 2504), SABE (n = 1171), and the full model (n = 3675) encompassing all samples. In extensive cross-validation of these reference panels, the multi-ethnic 1KG reference exhibited overall superior performance than the reference with only Brazilian samples. However, the best results were achieved with the full model. Additionally, we expanded the scope of imputation by developing reference panels for non-classical, MICA, MICB and HLA-H genes, previously unavailable for multi-ethnic populations. Validation in an independent Brazilian dataset showcased the superiority of our reference panels over the Michigan Imputation Server, particularly in predicting HLA-B alleles among Brazilians. Our investigations underscored the need to enhance or adapt reference panels to encompass the target population's genetic diversity, emphasising the significance of multiethnic references for accurate imputation across different populations.


Subject(s)
Alleles , Ethnicity , Gene Frequency , Polymorphism, Single Nucleotide , Humans , Brazil , Ethnicity/genetics , HLA Antigens/genetics , Linkage Disequilibrium , Genome-Wide Association Study/methods , Genotype , Genetics, Population/methods , Histocompatibility Antigens Class I/genetics , Computational Biology/methods
3.
Int Rev Sport Exerc Psychol ; 17(1): 564-586, 2024.
Article in English | MEDLINE | ID: mdl-38835409

ABSTRACT

Athletes are exposed to various psychological and physiological stressors, such as losing matches and high training loads. Understanding and improving the resilience of athletes is therefore crucial to prevent performance decrements and psychological or physical problems. In this review, resilience is conceptualized as a dynamic process of bouncing back to normal functioning following stressors. This process has been of wide interest in psychology, but also in the physiology and sports science literature (e.g. load and recovery). To improve our understanding of the process of resilience, we argue for a collaborative synthesis of knowledge from the domains of psychology, physiology, sports science, and data science. Accordingly, we propose a multidisciplinary, dynamic, and personalized research agenda on resilience. We explain how new technologies and data science applications are important future trends (1) to detect warning signals for resilience losses in (combinations of) psychological and physiological changes, and (2) to provide athletes and their coaches with personalized feedback about athletes' resilience.

4.
J Vasc Surg ; 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38904579

ABSTRACT

BACKGROUND: This study reports the 30-day outcomes of the primary arm of the GORE EXCLUDER Thoracoabdominal Branch Endoprosthesis (TAMBE) pivotal trial for complex abdominal aortic aneurysm repair. METHODS: This multicenter, nonrandomized, prospective study of the TAMBE device included patients enrolled in the primary study arm of extent IV thoracoabdominal aortic aneurysms and pararenal aneurysms. Technical success and major adverse events were analyzed per the Society for Vascular Surgery guidelines. RESULTS: The 102 patients of the primary arm who underwent endovascular repair using the TAMBE device were a mean age of 73 ± 6.4 years (range, 58-82 years) and 84 (84.2%) were male. The mean body mass index was 28.3 ± 5.0 kg/m2. Fifty-nine patients (57.8%) were treated for extent IV and 43 (42.2%) pararenal aneurysms; the mean maximum diameter of the aneurysms was 59.4 ± 7.8 mm. A prophylactic cerebral spinal fluid drain was used in 10 patients (9.8%). Technical success was achieved in 99% of patients, with the single failure owing to unsuccessful cannulation of the left renal artery. Mean procedure time was 315 ± 103 minutes (range, 163-944 minutes), estimated blood loss was 300 ± 296 mL (range, 10-2000 mL), and contrast administration was 153.6 ± 73.5 mL (range, 16-420 mL). The intensive care unit length of stay was 58.7 ± 52.7 hours (range, 1-288 mL). In 28 patients (27.5%), a total of 32 additional endovascular components were deployed to manage procedural complications including aortic and target vessel dissections and injuries not related to access. Bridging stent grafts were deployed to incorporate 407 target vessels (mean 1.6/per vessel; range, 1-4). Postoperative transfusion was required in 14 patients (13.7%). Major adverse events occurred in seven patients (6.9%) through 30 days. Events included respiratory failure (n = 2), disabling stroke (n = 1), new-onset renal failure requiring dialysis (n = 2), and paraplegia (n = 2). At 30 days, there was one patient with intraoperative rupture; no severe bowel ischemia or lesion-related/all-cause mortality were reported. The Core lab-reported patency was 100% in the aortic component, superior mesenteric artery, and celiac artery, and 95.9% in the left renal and 99.0% in the right renal branch components through 30 days of follow-up. Reinterventions through 30 days were performed in 9 of 96 patients (9.4%) and were all minor. CONCLUSIONS: Early TAMBE device outcomes demonstrate a high technical success rate, no 30-day lesion-related mortality, and a low rate of safety events within 30 days of the index procedure.

5.
J Sports Sci ; 42(2): 189-199, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38451830

ABSTRACT

The Acute Recovery and Stress Scale (ARSS) and the Short Recovery and Stress Scale (SRSS) are recently-introduced instruments to monitor recovery and stress processes in athletes. In this study, our aims were to replicate and extend previous psychometric assessments of the instruments, by incorporating recovery and stress dimensions into one model. Therefore, we conducted five confirmatory factor analyses (CFA) and determined structural validity, internal consistency, and construct validity. Dutch and Flemish athletes (N = 385, 213 females, 170 males, 2 others, 21.03 ± 5.44 years) completed the translated ARSS and SRSS, the Recovery Stress Questionnaire for Athletes (RESTQ-Sport-76), the Rating of Perceived Exertion (RPE) and the Total Quality of Recovery (TQR). There was a good model fit for the replicated CFA, sub-optimal model fit for the models that incorporated recovery and stress into one model, and satisfactory internal consistency (α=.75 - .87). The correlations within and between the ARSS and SRSS, as well as between the ARSS/SRSS and the RESTQ-Sport-76 (r = .31 - -.77 for the ARSS, r = .28 - -.63 for the SRSS), the RPE (r = .19 - -.23), and the TQR (r = .63 - -.63) also supported construct validity. The combined findings support the use of the ARSS and SRSS to assess stress and recovery in sports-related research and practice.


Subject(s)
Athletes , Sports , Male , Female , Humans , Psychometrics , Surveys and Questionnaires , Factor Analysis, Statistical , Reproducibility of Results
6.
Ann Vasc Surg ; 104: 147-155, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38492730

ABSTRACT

BACKGROUND: Endovascular repair of blunt thoracic aortic injury (BTAI) has dramatically reduced the morbidity and mortality of intervention. Injuries requiring zone 2 coverage of the aorta traditionally require left subclavian artery (LSA) sacrifice or open revascularization. Furthermore, these injuries are associated with an increased risk of in-hospital mortality and long-term morbidity. Here we report 1-year outcomes of total endovascular repair of BTAI with the GORE® TAG® Thoracic Branch Endoprosthesis for LSA preservation. METHODS: Across 34 investigative sites, 9 patients with BTAI requiring LSA coverage were enrolled in a nonrandomized, prospective study of a single-branched aortic endograft. The thoracic branch endoprosthesis device allows for graft placement proximal to the LSA and incorporates a single side branch for LSA perfusion. RESULTS: This initial cohort included 8 male and 1 female patient with a median age of 43 (22, 76) and 12 months of follow-up. Five total years of follow-up are planned. All participants had grade 3 BTAI. All procedures took place between 2018 and 2019. The median injury severity score was 2 (0, 66). The median procedure time was 109 min (78, 162). All aortic injuries were repaired under general anesthesia and with heparinization. A spinal drain was used in one patient. Post-deployment balloon angioplasty was conducted in one case at the distal landing zone. There was one asymptomatic LSA branch occlusion 6 months after repair. It was attributed to the purposeful proximal deployment of the branch stent to accommodate an early vertebral takeoff. The occlusion did not require revascularization. There were no strokes, mortalities, or aortic adverse events (migration, endoleak, native aortic expansion, dissection, or thrombosis) through 12 months of follow-up. CONCLUSIONS: Initial cohort outcomes suggest that endovascular repair of zone 2 BTAI is feasible and has favorable outcomes using the thoracic branch device with LSA preservation. Additional cases and longer-term follow-up are required for a definitive assessment of the device's safety and durability in traumatic aortic injuries.


Subject(s)
Aorta, Thoracic , Blood Vessel Prosthesis Implantation , Blood Vessel Prosthesis , Endovascular Procedures , Prosthesis Design , Vascular System Injuries , Wounds, Nonpenetrating , Humans , Male , Wounds, Nonpenetrating/surgery , Wounds, Nonpenetrating/diagnostic imaging , Female , Vascular System Injuries/surgery , Vascular System Injuries/diagnostic imaging , Vascular System Injuries/mortality , Vascular System Injuries/etiology , Blood Vessel Prosthesis Implantation/instrumentation , Blood Vessel Prosthesis Implantation/adverse effects , Blood Vessel Prosthesis Implantation/mortality , Aorta, Thoracic/surgery , Aorta, Thoracic/diagnostic imaging , Aorta, Thoracic/injuries , Endovascular Procedures/instrumentation , Endovascular Procedures/adverse effects , Endovascular Procedures/mortality , Adult , Treatment Outcome , Middle Aged , Time Factors , Prospective Studies , Young Adult , Aged , Thoracic Injuries/surgery , Thoracic Injuries/diagnostic imaging , Thoracic Injuries/mortality , United States , Stents , Risk Factors
8.
Chirurgie (Heidelb) ; 95(2): 108-114, 2024 Feb.
Article in German | MEDLINE | ID: mdl-38191810

ABSTRACT

Lung transplantation is currently the gold standard treatment for end-stage lung diseases. Advances in the preservation of donor lungs, the surgical technique and immunosuppressive therapy have led to lung transplantation now being a routine procedure. Nevertheless, the shortage of donor organs, the acute and particularly chronic lung allograft dysfunction (CLAD) still represent major challenges even in experienced centers. Research in this area is still necessary to improve the long-term survival of lung recipients.


Subject(s)
Lung Transplantation , Humans , Immunosuppression Therapy , Lung/pathology , Lung/surgery , Lung Transplantation/methods , Lung Transplantation/trends , Thorax , Tissue Donors
9.
Ann Vasc Surg ; 101: 209-218, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38163582

ABSTRACT

BACKGROUND: Primary infected abdominal aortic aneurysms (PIAAAs) are associated with high morbidity and mortality. Three repair approaches include open in-situ repair (OIR), extra-anatomic repair (EAR), and endovascular abdominal aortic aneurysm repair (EVAR). This study is one of the largest single-center case series comparing the outcomes of the different surgical approaches for PIAAA. METHODS: This is a retrospective cohort study of all patients treated surgically for PIAAA between 2000 and 2021. PIAAA diagnosis was defined as the presence of an abdominal aortic aneurysm with evidence of infection on clinical presentation, laboratory markers, radiology, or surgically. Patients with prior aortic surgery were excluded from this study. Basic demographics were compared across the 3 surgical groups using standard statistical methods. Our primary outcomes included mortality at 1 and 5 years. Kaplan-Meier curves were generated and compared using log-rank testing. Multivariate Cox proportional hazards models were created to assess determinants of mortality. RESULTS: A total of 43 patients were included in the full cohort. Patients undergoing EVAR more often had diabetes, end-stage renal disease, and coronary artery disease. EVAR was also more often done in patients with a saccular aneurysm rather than fusiform. (93% vs. 70% in EAR and 42% in OIR; P = 0.015). All-cause mortality rates at 1 year were not significantly different between the 3 groups. Survival at 5 years did show a significant benefit of OIR over EVAR and EAR: OIR had an 8% mortality rate with EAR having a 53% rate and EVAR having the highest (72%) mortality rate at 5 years (P = 0.03). Multivariable Cox regression analysis showed that EVAR (aHR 12.1, (95% CI 1.42 to 103.9), P = 0.02) and EAR (aHR 15.1, (95% CI 1.59 to 143.3), P = 0.0.02) had an increased 5-year mortality risk when compared to OIR. CONCLUSIONS: Repair of primary infected aortic aneurysm is associated with high complication and mortality rates regardless of the approach. In our studied sample, OIR offered an improved long-term survival without added benefits in terms of complication rates. In infected AAA, EVAR should be considered bridging stage between the urgent situation and eventual open repair.


Subject(s)
Aortic Aneurysm, Abdominal , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Humans , Retrospective Studies , Treatment Outcome , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , Aortic Aneurysm, Abdominal/etiology , Aorta/surgery , Risk Factors , Blood Vessel Prosthesis Implantation/adverse effects , Postoperative Complications/etiology
10.
J Vasc Surg ; 79(4): 755-762, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38040202

ABSTRACT

OBJECTIVE: Limited data exist for optimal blood pressure (BP) management during transfer of patients with ruptured abdominal aortic aneurysm (rAAA). This study evaluates the effects of hypertension and severe hypotension during interhospital transfers in a cohort of patients with rAAA in hemorrhagic shock. METHODS: We performed a retrospective, single-institution review of patients with rAAA transferred via air ambulance to a quaternary referral center for repair (2003-2019). Vitals were recorded every 5 minutes in transit. Hypertension was defined as a systolic BP of ≥140 mm Hg. The primary cohort included patients with rAAA with hemorrhagic shock (≥1 episode of a systolic BP of <90 mm Hg) during transfer. The primary analysis compared those who experienced any hypertensive episode to those who did not. A secondary analysis evaluated those with either hypertension or severe hypotension <70 mm Hg. The primary outcome was 30-day mortality. RESULTS: Detailed BP data were available for 271 patients, of which 125 (46.1%) had evidence of hemorrhagic shock. The mean age was 74.2 ± 9.1 years, 93 (74.4%) were male, and the median total transport time from helicopter dispatch to arrival at the treatment facility was 65 minutes (interquartile range, 46-79 minutes). Among the cohort with shock, 26.4% (n = 33) had at least one episode of hypertension. There were no significant differences in age, sex, comorbidities, AAA repair type, AAA anatomic location, fluid resuscitation volume, blood transfusion volume, or vasopressor administration between the hypertensive and nonhypertensive groups. Patients with hypertension more frequently received prehospital antihypertensives (15% vs 2%; P = .01) and pain medication (64% vs 24%; P < .001), and had longer transit times (36.3 minutes vs 26.0 minutes; P = .006). Episodes of hypertension were associated with significantly increased 30-day mortality on multivariable logistic regression (adjusted odds ratio [aOR], 4.71; 95% confidence interval [CI], 1.54-14.39; P = .007; 59.4% [n = 19] vs 40.2% [n = 37]; P = .01). Severe hypotension (46%; n = 57) was also associated with higher 30-day mortality (aOR, 2.82; 95% CI, 1.27-6.28; P = .01; 60% [n = 34] vs 32% [n = 22]; P = .01). Those with either hypertension or severe hypotension (54%; n = 66) also had an increased odds of mortality (aOR, 2.95; 95% CI, 1.08-8.11; P = .04; 58% [n = 38] vs 31% [n = 18]; P < .01). Level of hypertension, BP fluctuation, and timing of hypertension were not significantly associated with mortality. CONCLUSIONS: Hypertensive and severely hypotensive episodes during interhospital transfer were independently associated with increased 30-day mortality in patients with rAAA with shock. Hypertension should be avoided in these patients, but permissive hypotension approaches should also maintain systolic BPs above 70 mm Hg whenever possible.


Subject(s)
Aortic Aneurysm, Abdominal , Aortic Rupture , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Hypertension , Hypotension , Shock, Hemorrhagic , Humans , Male , Aged , Aged, 80 and over , Female , Shock, Hemorrhagic/therapy , Retrospective Studies , Hypotension/etiology , Hypertension/complications , Aortic Rupture/diagnostic imaging , Aortic Rupture/surgery , Aortic Rupture/complications , Aortic Aneurysm, Abdominal/complications , Aortic Aneurysm, Abdominal/diagnostic imaging , Aortic Aneurysm, Abdominal/surgery , Treatment Outcome , Risk Factors
11.
HLA ; 103(1): e15282, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37950640

ABSTRACT

Human genomics has quickly evolved, powering genome-wide association studies (GWASs). SNP-based GWASs cannot capture the intense polymorphism of HLA genes, highly associated with disease susceptibility. There are methods to statistically impute HLA genotypes from SNP-genotypes data, but lack of diversity in reference panels hinders their performance. We evaluated the accuracy of the 1000 Genomes data as a reference panel for imputing HLA from admixed individuals of African and European ancestries, focusing on (a) the full dataset, (b) 10 replications from 6 populations, and (c) 19 conditions for the custom reference panels. The full dataset outperformed smaller models, with a good F1-score of 0.66 for HLA-B. However, custom models outperformed the multiethnic or population models of similar size (F1-scores up to 0.53, against up to 0.42). We demonstrated the importance of using genetically specific models for imputing populations, which are currently underrepresented in public datasets, opening the door to HLA imputation for every genetic population.


Subject(s)
Genetics, Population , Genome-Wide Association Study , Humans , Alleles , Genotype , HLA-B Antigens , Polymorphism, Single Nucleotide
12.
Emerg Infect Dis ; 30(1): 155-158, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38147057

ABSTRACT

After reports in 2017 of Brucella neotomae infections among humans in Costa Rica, we sequenced 12 strains isolated from rodents during 1955-1964 from Utah, USA. We observed an exact strain match between the human isolates and 1 Utah isolate. Independent confirmation is required to clarify B. neotomae zoonotic potential.


Subject(s)
Brucella , Brucellosis , Humans , Genomics , Brucella/genetics , Brucellosis/epidemiology , Brucellosis/veterinary , Costa Rica/epidemiology
13.
Sci Med Footb ; : 1-9, 2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38059842

ABSTRACT

This study assessed the discriminative validity of summarized hip and knee angular accelerations during a standardized training drill. Twenty-eight soccer players performed a standardized training drill that mimics game demands. Discriminative validity was examined by assessment of between-group differences of summarized preferred kicking leg hip and knee angular accelerations, and Playerload between national and regional soccer players for the full training drill, and parts based on locomotor intensity, or additional pass and jumping header activities. Furthermore, relationships were assessed between the summarized hip and knee angular accelerations and conventional load indicators derived from a local positioning measurement system, such as high-intensity running distance and Playerload. National players had higher summarized hip (Mean difference: 62.7 A.U. ES = 0.77, p = 0.049) and knee (Mean difference: 137.1 A.U. ES = 1.06, p = 0.008) angular accelerations. Significant interaction effects were observed during high-intensity running (Hip: 0.2 A.U./m, ES = 0.98, p = 0.005; Knee: 0.61 A.U./m, ES = 1.52, p < 0.001), and sprinting (Hip: 0.3 A.U./m, ES = 1.01, p < 0.02; Knee: 0.56 A.U./m, ES = 1.57, p < 0.001). Between-group differences were not present for additional passing or jumping header activities. Compared to summarized hip and knee angular accelerations, Playerload had less ability to discriminate between players and activities. Moreover, the lower extremity training load indicators were unrelated to conventional load indicators. Together these results confirm discriminative validity of summarized hip and knee angular acceleration training load indicators during a standardised training drill.


The results in this study substantiate the use and validity of summarized hip and knee angular accelerations as external training load indicators for the lower extremities in soccer. Based on the known-group difference technique, expected differences in summarized hip and knee angular accelerations between national and regional soccer players were observed during a standardized soccer training drill. These differences were present during high intensity running and sprint activities, but not for passing or jumping header activities. The limited ability of Playerload to discriminate between players and tasks, and insignificant relationships between measurement systems in this study demonstrate that summarized hip and knee angular accelerations can be used complementary to whole-body training load indicators for evaluating soccer training and match play. The presented methodology provides insights in the training load of individual limbs, which potentially can be used to assess the effectiveness of specific training drills to under- or overload specific limbs. Trainers, coaches, and sport practitioners can use this information to balance training load and recovery in soccer, aiming to improve performance and prevent overload.

15.
Article in English | MEDLINE | ID: mdl-37875336

ABSTRACT

BACKGROUND: Hereditary transthyretin amyloidosis is a life-threatening autosomal dominant systemic disease due to pathogenic TTR variants (ATTRv), mostly affecting the peripheral nerves and heart. The disease is characterised by a combination of symptoms, organ involvement and histological amyloid deposition. The available disease-modifying ATTRv treatments (DMTs) are more effective if initiated early. Pathological nerve conduction studies (NCS) results are the cornerstone of large-fibre polyneuropathy diagnosis, but this anomaly occurs late in the disease. We investigated the utility of a multimodal neurological and cardiac evaluation for detecting early disease onset in ATTRv carriers. METHODS: We retrospectively analysed a cohort of ATTRv carriers with normal NCS results regardless of symptoms. Multimodal denervation and infiltration evaluations included a clinical questionnaire (Lauria and New York Heart Association (NYHA)) and examination, intra-epidermal nerve fibre density assessment, autonomic assessment based on heart rate variability, Sudoscan, meta-iodo-benzyl-guanidine scintigraphy, cardiac biomarkers, echocardiography, MRI and searches for amyloidosis on skin biopsy and bone scintigraphy. RESULTS: We included 130 ATTRv carriers (40.8% men, age: 43.6±13.5 years), with 18 amyloidogenic TTR gene mutations, the majority of which was the late-onset Val30Met variant (42.3%). Amyloidosis was detected in 16.9% of mutation carriers, including 9 (6.9%) with overt disease (Lauria>2 or NYHA>1) and 13 asymptomatic carriers (10%) with organ involvement (small-fibre neuropathy or cardiomyopathy). Most of these patients received DMT. Abnormal test results of unknown significance were obtained for 105 carriers (80.8%). Investigations were normal in only three carriers (2.3%). CONCLUSIONS: Multimodal neurological and cardiac investigation of TTRv carriers is crucial for the early detection of ATTRv amyloidosis and initiation of DMT.

16.
Sci Rep ; 13(1): 14571, 2023 Sep 04.
Article in English | MEDLINE | ID: mdl-37666909

ABSTRACT

The emerging CdTe-BeTe semiconductor alloy that exhibits a dramatic mismatch in bond covalency and bond stiffness clarifying its vibrational-mechanical properties is used as a benchmark to test the limits of the percolation model (PM) worked out to explain the complex Raman spectra of the related but less contrasted Zn1-xBex-chalcogenides. The test is done by way of experiment ([Formula: see text]), combining Raman scattering with X-ray diffraction at high pressure, and ab initio calculations ([Formula: see text] ~ 0-0.5; [Formula: see text]~1). The (macroscopic) bulk modulus [Formula: see text] drops below the CdTe value on minor Be incorporation, at variance with a linear [Formula: see text] versus [Formula: see text] increase predicted ab initio, thus hinting at large anharmonic effects in the real crystal. Yet, no anomaly occurs at the (microscopic) bond scale as the regular bimodal PM-type Raman signal predicted ab initio for Be-Te in minority ([Formula: see text]~0, 0.5) is barely detected experimentally. At large Be content ([Formula: see text]~1), the same bimodal signal relaxes all the way down to inversion, an unprecedented case. However, specific pressure dependencies of the regular ([Formula: see text]~0, 0.5) and inverted ([Formula: see text]~1) Be-Te Raman doublets are in line with the predictions of the PM. Hence, the PM applies as such to Cd1-xBexTe without further refinement, albeit in a "relaxed" form. This enhances the model's validity as a generic descriptor of phonons in alloys.

17.
Cell Rep ; 42(8): 112830, 2023 08 29.
Article in English | MEDLINE | ID: mdl-37481724

ABSTRACT

MYC proto-oncogene dysregulation alters metabolism, translation, and other functions in ways that support tumor induction and maintenance. Although Myc+/- mice are healthier and longer-lived than control mice, the long-term ramifications of more complete Myc loss remain unknown. We now describe the chronic consequences of body-wide Myc inactivation initiated postnatally. "MycKO" mice acquire numerous features of premature aging, including altered body composition and habitus, metabolic dysfunction, hepatic steatosis, and dysregulation of gene sets involved in functions that normally deteriorate with aging. Yet, MycKO mice have extended lifespans that correlate with a 3- to 4-fold lower lifetime cancer incidence. Aging tissues from normal mice and humans also downregulate Myc and gradually alter many of the same Myc target gene sets seen in MycKO mice. Normal aging and its associated cancer predisposition are thus highly linked via Myc.


Subject(s)
Aging, Premature , Neoplasms , Humans , Mice , Animals , Aging, Premature/genetics , Proto-Oncogene Proteins c-myc/genetics , Proto-Oncogene Proteins c-myc/metabolism , Incidence , Neoplasms/pathology , Aging
19.
J Plast Reconstr Aesthet Surg ; 85: 202-209, 2023 10.
Article in English | MEDLINE | ID: mdl-37524032

ABSTRACT

BACKGROUND: Enhanced recovery after surgery (ERAS) programs are associated with improved management, reduced hospital stays, and lower complication rates. OBJECTIVE: To evaluate the impact of ERAS on mean length of stay (LOS) and postoperative morbidity in breast reconstruction with latissimus dorsi flap (LDF) compared with conventional recovery program. PATIENTS AND METHOD: All patients operated by LDF between December 2014 and October 2020: those managed before April 2018, when the ERAS protocol was introduced, were included in the "no ERAS" group, and beyond in the "ERAS" group. RESULTS: Out of 193 patients, 129 were included in the "ERAS" group and 64 in the "no ERAS" group. There was a significant difference between the two groups in LOS (4.2 ± 1.5 days in the "ERAS" group vs. 5.4 ± 1.9 days in the "no ERAS" group; p < 0.001), high-grade complications at 30 days (9.3% in the "ERAS" group vs. 25% in the "no ERAS" group; p = 0.01), reintervention rate (13.9% vs. 26.6%, respectively; p = 0.02), and 30-day rehospitalization rate (6.2% in the "ERAS" group vs. 15.6% in the "no ERAS" group; p = 0.03). CONCLUSION: The ERAS protocol has a positive impact on breast reconstruction with LDF without generating additional adverse effects. These results support the democratization of these programs for breast reconstruction surgery.


Subject(s)
Enhanced Recovery After Surgery , Mammaplasty , Superficial Back Muscles , Humans , Superficial Back Muscles/transplantation , Postoperative Complications/etiology , Mammaplasty/methods , Surgical Flaps , Length of Stay , Retrospective Studies
20.
J Vasc Surg ; 78(4): 945-953.e3, 2023 10.
Article in English | MEDLINE | ID: mdl-37385354

ABSTRACT

BACKGROUND: Multiple organ failure (MOF) is associated with poor outcomes and increased mortality in sepsis and trauma. There are limited data regarding MOF in patients after ruptured abdominal aortic aneurysm (rAAA) repair. We aimed to identify the contemporary prevalence and characteristics of patients with rAAA with MOF. METHODS: We retrospectively reviewed patients with rAAA who underwent repair (2010-2020) at our multihospital institution. Patients who died within the first 2 days after repair were excluded. MOF was quantified by modified (excluding hepatic system) Denver, Sequential Organ Failure Assessment (SOFA) score, and Multiple Organ Dysfunction Score (MODS) for postoperative days 3 to 5 to determine the prevalence of MOF. MOF was defined as a Denver score of >3, dysfunction in two or more organ systems by SOFA score, or a MODS score of >8. Kaplan-Meier curves and log-rank testing were used to evaluate differences in 30-day mortality between multiple organ failure and patients without MOF. Logistic regression was used to assess predictors of MOF. RESULTS: Of 370 patients with rAAA, 288 survived past two days (mean age, 73±10.1 years; 76.7% male; 44.1% open repair), and 143 had data for MOF calculation recorded. From postoperative days 3 to 5, 41 (14.24%) had MOF by Denver, 26 (9.03%) by SOFA, and 39 (13.54%) by MODS criteria. Among these scoring systems, pulmonary and neurological systems were impacted most commonly. Among patients with MOF, pulmonary derangement occurred in 65.9% (Denver), 57.7% (SOFA), and 56.4% (MODS). Similarly, neurological derangement occurred in 92.3% (SOFA) and 89.7% (MODS), but renal derangement occurred in 26.8% (Denver), 23.1% (SOFA), and 10.3% (MODS). MOF by all three scoring systems was associated with increased 30-day mortality (Denver: 11.3% vs 41.5% [P < .01]; DOFA: 12.6% vs 46.2% [P < .01]; MODS: 12.5% vs 35.9% [P < .01]), as was MOF by any criteria (10.8% vs 35.7 %; P < .01). Patients with MOF were more likely to have a higher body mass index (55.9±26.6 vs 49.0±15.0; P = .011) and to have had a preoperative stroke (17.9% vs 6.0%; P = .016). Patients with MOF were less likely to have undergone endovascular repair (30.4% vs 62.1%; P < .001). Endovascular repair was protective against MOF (any criteria) on multivariate analysis (odds ratio, 0.23; 95% confidence interval, 0.08-0.64; P = .019) after adjusting for age, gender, and presenting systolic blood pressure. CONCLUSIONS: MOF occurred in only 9% to 14% of patients after rAAA repair, but was associated with a three-fold increase in mortality. Endovascular repair was associated with a reduced MOF incidence.


Subject(s)
Aortic Aneurysm, Abdominal , Aortic Rupture , Blood Vessel Prosthesis Implantation , Endovascular Procedures , Humans , Male , Middle Aged , Aged , Aged, 80 and over , Female , Multiple Organ Failure/diagnosis , Multiple Organ Failure/epidemiology , Multiple Organ Failure/etiology , Retrospective Studies , Endovascular Procedures/adverse effects , Blood Pressure , Treatment Outcome , Risk Factors , Blood Vessel Prosthesis Implantation/adverse effects
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