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1.
Eur Heart J Imaging Methods Pract ; 2(1): qyae035, 2024 Jan.
Article in English | MEDLINE | ID: mdl-39045181

ABSTRACT

Aims: A comparison of diagnostic performance comparing AI-QCTISCHEMIA, coronary computed tomography angiography using fractional flow reserve (CT-FFR), and physician visual interpretation on the prediction of invasive adenosine FFR have not been evaluated. Furthermore, the coronary plaque characteristics impacting these tests have not been assessed. Methods and results: In a single centre, 43-month retrospective review of 442 patients referred for coronary computed tomography angiography and CT-FFR, 44 patients with CT-FFR had 54 vessels assessed using intracoronary adenosine FFR within 60 days. A comparison of the diagnostic performance among these three techniques for the prediction of FFR ≤ 0.80 was reported. The mean age of the study population was 65 years, 76.9% were male, and the median coronary artery calcium was 654. When analysing the per-vessel ischaemia prediction, AI-QCTISCHEMIA had greater specificity, positive predictive value (PPV), diagnostic accuracy, and area under the curve (AUC) vs. CT-FFR and physician visual interpretation CAD-RADS. The AUC for AI-QCTISCHEMIA was 0.91 vs. 0.76 for CT-FFR and 0.62 for CAD-RADS ≥ 3. Plaque characteristics that were different in false positive vs. true positive cases for AI-QCTISCHEMIA were max stenosis diameter % (54% vs. 67%, P < 0.01); for CT-FFR were maximum stenosis diameter % (40% vs. 65%, P < 0.001), total non-calcified plaque (9% vs. 13%, P < 0.01); and for physician visual interpretation CAD-RADS ≥ 3 were total non-calcified plaque (8% vs. 12%, P < 0.01), lumen volume (681 vs. 510 mm3, P = 0.02), maximum stenosis diameter % (40% vs. 62%, P < 0.001), total plaque (19% vs. 33%, P = 0.002), and total calcified plaque (11% vs. 22%, P = 0.003). Conclusion: Regarding per-vessel prediction of FFR ≤ 0.8, AI-QCTISCHEMIA revealed greater specificity, PPV, accuracy, and AUC vs. CT-FFR and physician visual interpretation CAD-RADS ≥ 3.

2.
JHLT Open ; 32024 Feb.
Article in English | MEDLINE | ID: mdl-39015662

ABSTRACT

Background: Myocarditis is a common cause of pediatric heart failure which may require mechanical circulatory support (MCS). The purpose of this study is to describe MCS strategies used in a nationwide cohort of pediatric patients with myocarditis, identify trends over time, and compare outcomes between MCS strategies. Methods: This study utilized the Kids' Inpatient Database (KID), a national sample of administrative discharge data. KID admissions from 2003-2016 were queried using ICD-9/10 codes to identify those with a diagnosis of myocarditis. MCS outcomes were compared using logistic regression. Results: Of 5,661 admissions for myocarditis, MCS was used in 424 (7.5%), comprised of extracorporeal membrane oxygenation (ECMO) in 312 (73.6%), including 32 (10.2%) instances of extracorporeal cardiopulmonary resuscitation (ECPR), temporary ventricular assist devices (tVAD) in 28 (6.6%), durable VAD (dVAD) in 42 (9.9%) and combination MCS in 42 (9.9%). MCS use increased over time (p=0.031), but MCS strategies did not significantly change. Mortality was high in the MCS group (28.3%). There was no difference in odds of death in the VAD only or combination MCS group compared to the non-ECPR ECMO group (p=0.07 and p=0.65, respectively). Conclusion: MCS is used in 1 in 13 pediatric myocarditis cases, and MCS use is increasing over time with ECMO remaining the most frequently used modality. Mortality remains high in patients that receive MCS but does not differ between those receiving VAD or combination MCS as compared to non-ECPR ECMO on unadjusted analysis. Further prospective analysis is required to evaluate the relative effectiveness of MCS modalities in this disease.

3.
Physiol Rep ; 12(14): e16149, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39016164

ABSTRACT

The purpose of this study was to investigate whether endothelin-A receptor (ETAR) inhibition in non-Hispanic Black (NHB) and White (NHW) young adults depends on biological sex. We recruited females during low hormone (n = 22) and high hormone (n = 22) phases, and males (n = 22). Participants self-identified as NHB (n = 33) or NHW (n = 33). Participants were instrumented with two microdialysis fibers: (1) lactated Ringer's (control) and (2) 500 nM BQ-123 (ETAR antagonist). Local heating was used to elicit cutaneous vasodilation, and an infusion of 20 mM L-NAME to quantify NO-dependent vasodilation. At control sites, NO-dependent vasodilation was lowest in NHB males (46 ± 13 %NO) and NHB females during low hormone phases (47 ± 12 %NO) compared to all NHW groups. Inhibition of ETAR increased NO-dependent vasodilation in NHB males (66 ± 13 %NO), in both groups of females during low hormone phases (NHW, control: 64 ± 12 %NO, BQ-123: 85 ± 11 %NO; NHB, BQ-123: 68 ± 13 %NO), and in NHB females during high hormone phases (control: 61 ± 11 %NO, BQ-123: 83 ± 9 %NO). There was no effect for ETAR inhibition in NHW males or females during high hormone phases. These data suggest the effect of ETAR inhibition on NO-dependent vasodilation is influenced by biological sex and racial identity.


Subject(s)
Endothelin A Receptor Antagonists , Peptides, Cyclic , Receptor, Endothelin A , Skin , Vasodilation , Adult , Female , Humans , Male , Young Adult , Endothelin A Receptor Antagonists/pharmacology , Microvessels/physiology , Microvessels/drug effects , Microvessels/metabolism , Nitric Oxide/metabolism , Peptides, Cyclic/pharmacology , Receptor, Endothelin A/metabolism , Sex Characteristics , Skin/blood supply , Skin/metabolism , Vasodilation/drug effects , Black or African American , White
4.
iScience ; 27(7): 109978, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39021796

ABSTRACT

High-grade serous ovarian cancers (HGSOCs) with homologous recombination deficiency (HRD) are initially responsive to poly (ADP-ribose) polymerase inhibitors (PARPi), but resistance ultimately emerges. HGSOC with CCNE1 amplification (CCNE1 amp) are associated with resistance to PARPi and platinum treatments. High replication stress in HRD and CCNE1 amp HGSOC leads to increased reliance on checkpoint kinase 1 (CHK1), a key regulator of cell cycle progression and the replication stress response. Here, we investigated the anti-tumor activity of the potent, highly selective, orally bioavailable CHK1 inhibitor (CHK1i), SRA737, in both acquired PARPi-resistant BRCA1/2 mutant and CCNE1 amp HGSOC models. We demonstrated that SRA737 increased replication stress and induced subsequent cell death in vitro. SRA737 monotherapy in vivo prolonged survival in CCNE1 amp models, suggesting a potential biomarker for CHK1i therapy. Combination SRA737 and PARPi therapy increased tumor regression in both PARPi-resistant and CCNE1 amp patient-derived xenograft models, warranting further study in these HGSOC subgroups.

5.
Mol Genet Metab Rep ; 40: 101110, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39022300

ABSTRACT

Treatment of phenylketonuria (PKU) has evolved since the initial introduction of a phenylalanine (Phe) restricted diet. The most recent option for adults affected with PKU is treatment with an alternate enzyme, phenylalanine ammonia lyase (PAL), that metabolizes excess Phe. Proper management of all patients with PKU relies on accurate measurement of Phe levels in blood, to comply with guidance intended to minimize the neurological symptoms. Recently, our laboratory was notified of discrepant results for a patient with PKU who is treated with pegvaliase. Two specimens were collected at the same time but yielded unexpectedly different Phe concentrations. After exclusion of specimen mix-ups or analytical errors, we suspected that there was residual pegvaliase activity in the specimens continuing to degrade Phe after collection. To investigate this possibility, we performed spiking studies that showed the degradation of Phe over time at ambient temperatures. Sample preparation by protein crash appears to deactivate pegvaliase and prevents further Phe degradation. However, because pegvaliase deactivation would be required immediately following blood collection, appropriate mitigation measures must be implemented, including stringent pre-analytical requirements, alternate sample matrices such as dried blood spots, or point of care testing. Until then, health care professionals need to be cautious in their interpretation of Phe levels in their patients with PKU that are treated with pegvaliase.

6.
Article in English | MEDLINE | ID: mdl-39024049

ABSTRACT

OBJECTIVES: To examine the clinicopathologic features of patients with polymyalgia rheumatica (PMR) who had thoracic aorta repair surgery. Findings were compared with those of a cohort of patients with giant cell arteritis (GCA) requiring thoracic aorta repair. METHODS: All patients evaluated at Mayo Clinic in Rochester, MN, with Current Procedural Terminology (CPT) codes for thoracic aorta repair surgery between 2000- 2021 were identified. All patients were screened for prior PMR diagnosis. Patients with PMR and no signs of GCA were categorized as clinically isolated PMR. The medical records of all patients were manually reviewed, and pathologists re-examined all the aortic tissues. RESULTS: Of the 4621 patients with at least one CPT code for thoracic aorta repair surgery, 43 patients were diagnosed with clinically isolated PMR before the surgery. Detailed histopathological examination of the aortic tissues revealed active inflammation in 30/43 (70%) patients after a median (IQR) of 10.0 (4.7- 13.3) years from the PMR diagnosis. When compared with aortic tissue from patients with a prior diagnosis of GCA, the aorta of patients with PMR had more severe inflammation (Grade 3: 15/30 [50%] vs 5/34 [15%], p= 0.002). Patients with PMR and thoracic aorta repair may experience a 40% increased risk of mortality compared with the general population, but this did not reach statistical significance (standardized mortality ratio: 1.40; 95% CI: 0.91- 2.07). CONCLUSIONS: Some patients with PMR have subclinical aortic inflammation that is detectable many years after initial diagnosis and may contribute to the development of aortic aneurysm.

7.
J Am Chem Soc ; 146(28): 19146-19159, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38953583

ABSTRACT

Van der Waals (vdW) magnets both allow exploration of fundamental 2D physics and offer a route toward exploiting magnetism in next generation information technology, but vdW magnets with complex, noncollinear spin textures are currently rare. We report here the syntheses, crystal structures, magnetic properties and magnetic ground states of four bulk vdW metal-organic magnets (MOMs): FeCl2(pym), FeCl2(btd), NiCl2(pym), and NiCl2(btd), pym = pyrimidine and btd = 2,1,3-benzothiadiazole. Using a combination of neutron diffraction and bulk magnetometry we show that these materials are noncollinear magnets. Although only NiCl2(btd) has a ferromagnetic ground state, we demonstrate that low-field hysteretic metamagnetic transitions produce states with net magnetization in zero-field and high coercivities for FeCl2(pym) and NiCl2(pym). By combining our bulk magnetic data with diffuse scattering analysis and broken-symmetry density-functional calculations, we probe the magnetic superexchange interactions, which when combined with symmetry analysis allow us to suggest design principles for future noncollinear vdW MOMs. These materials, if delaminated, would prove an interesting new family of 2D magnets.

8.
Surgery ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39025691

ABSTRACT

BACKGROUND: Management of esophageal perforation includes open surgery, minimally invasive surgery, and endoscopic stent placement. This study analyzed initial treatment and the associated short-term outcomes. METHODS: A retrospective study using the National Inpatient Sample between October 2015 and December 2019 identified adults >18 years with esophageal perforation undergoing an initial nonelective esophageal procedure categorized into either open surgery, minimally invasive surgery, or endoscopic stent placement. Patients with esophageal cancer were excluded. Baseline characteristics and the van Walraven-weighted Elixhauser Comorbidity Index were identified. Outcomes included in-hospital mortality and postintervention complications. Univariable and multivariable Cox regression was used to compare in-hospital survival. RESULTS: In total, 3,345 patients met inclusion criteria: the median age was 62 years (interquartile range 50-72 years), and 1,310 (39%) were female. Open procedure was pursued in 2,650 (79%), minimally invasive surgery in 310 (9%), and endoscopic stent placement in 385 (12%) with no differences in van Walraven-weighted Elixhauser Comorbidity Index or mortality. Patients who underwent minimally invasive surgery had a greater proportion of gastrointestinal complications (P = .006); otherwise, there were no differences in postintervention complications. In total, 380 (11%) patients died and were significantly older, with greater van Walraven-weighted Elixhauser Comorbidity Index, and had more postintervention complications. Univariable Cox regression identified age (hazard ratio 1.95, P < .001), van Walraven-weighted Elixhauser Comorbidity Index (hazard ratio 1.06, P < .001), stent placement (hazard ratio 1.93, P = .045), and transfer from a health facility (HR 2.40, P = .049) as associated with decreased in-hospital survival. Multivariable Cox regression revealed age (hazard ratio 1.041, P < .001) and van Walraven-weighted Elixhauser comorbidity index (hazard ratio 1.055, P < .001) were associated with decreased in-hospital survival. CONCLUSION: Patients with esophageal perforation had an 11% in-hospital mortality rate and significant associated complications regardless of intervention. Increasing age and comorbidities are associated with poorer in-hospital survival.

9.
Exp Mol Med ; 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-39026032

ABSTRACT

Patients with chronic liver disease (CLD) often present with significant frailty, sarcopenia, and impaired immune function. However, the mechanisms driving the development of these age-related phenotypes are not fully understood. To determine whether accelerated biological aging may play a role in CLD, epigenetic, transcriptomic, and phenotypic assessments were performed on the skeletal muscle tissue and immune cells of CLD patients and age-matched healthy controls. Accelerated biological aging of the skeletal muscle tissue of CLD patients was detected, as evidenced by an increase in epigenetic age compared with chronological age (mean +2.2 ± 4.8 years compared with healthy controls at -3.0 ± 3.2 years, p = 0.0001). Considering disease etiology, age acceleration was significantly greater in both the alcohol-related (ArLD) (p = 0.01) and nonalcoholic fatty liver disease (NAFLD) (p = 0.0026) subgroups than in the healthy control subgroup, with no age acceleration observed in the immune-mediated subgroup or healthy control subgroup (p = 0.3). The skeletal muscle transcriptome was also enriched for genes associated with cellular senescence. Similarly, blood cell epigenetic age was significantly greater than that in control individuals, as calculated using the PhenoAge (p < 0.0001), DunedinPACE (p < 0.0001), or Hannum (p = 0.01) epigenetic clocks, with no difference using the Horvath clock. Analysis of the IMM-Age score indicated a prematurely aged immune phenotype in CLD patients that was 2-fold greater than that observed in age-matched healthy controls (p < 0.0001). These findings suggested that accelerated cellular aging may contribute to a phenotype associated with advanced age in CLD patients. Therefore, therapeutic interventions to reduce biological aging in CLD patients may improve health outcomes.

10.
bioRxiv ; 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-39026821

ABSTRACT

Homozygous DNAJC12 c.79-2A>G (p. V27Wfs*14) loss-of-function mutations were first reported as a cause of young-onset Parkinson's disease. However, bi-allelic autosomal recessive pathogenic variants in DNAJC12 may lead to an alternative constellation of neurological features including infantile dystonia, developmental delay, intellectual disability and neuropsychiatric disorders. DNAJC12 is understood to co-chaperone aromatic amino acid hydroxylases to enhance the synthesis of biogenic amines. In vitro , we confirm overexpressed DNAJC12 forms a complex with tyrosine hydroxylase, the rate-limiting enzyme in dopamine (DA) synthesis. Now we describe a conditional knockout mouse (cDKO) in which loxP sites flanking Dnajc12 exon 2 enable its excision by cre-recombinase to create a constitutive Dnajc12 knock out (DKO). At three months of age, DKO animals exhibit reduced locomotion and exploratory behavior in automated open-field testing. DKO mice also manifest increased plasma phenylalanine levels, a cardinal feature of patients with DNAJC12 pathogenic variants. In striatal tissue, total DA and serotonin, and their metabolites, are reduced. Biochemical alterations in synaptic proteins and tyrosine hydroxylase are also apparent, with enhanced phosphorylation of pSer31 and pSer40 sites that may reflect biological compensation. Electrically-evoked striatal DA is reduced. Most immediately, cDKO and DKO mice present models to develop and refined therapeutic approaches for the treatment of DNAJC12 dystonia and parkinsonism. These models may also enable the pleiotropic functions of biogenic amines (including DA) to be individually investigated in the brain and periphery.

11.
Nanoscale ; 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-39028306

ABSTRACT

Macromolecule branching upon polyhedral oligomeric silsesquioxanes (POSS) via "click" chemistry has previously been reported for promoting natural biological responses in vitro, particularly when regarding their demonstrated biocompatibility and structural robustness as potential macromolecule anchoring points. However, "clicking" of large molecules around POSS structures uncovers two main challenges: (1) a synthetic challenge encompassing multi-covalent attachment of macromolecules to a single nanoscale-central position, and (2) purification and separation of fully adorned nanocages from those that are incomplete due to their similar physical characteristics. Here we present peptide decoration to a T8POSS nanocage through the attachment of azido-modified trimers. Triglycine- and trialanine-methyl esters "clicked" to 97% and 92% completion, respectively, resulting in 84% and 68% yields of the fully-adorned octamers. The "clicks" halt within 27-h of the reaction time, and efforts to further increase the octamer yield were of negligible benefit. Exploration of reaction conditions reveals multiple factors preventing full octa-arm modification to all available POSS nanocages, and offers insights into macromolecule attachment between both peptides and small inorganic-organic structures, all of which require consideration for future work of this nature.

12.
Int J Palliat Nurs ; 30(7): 370-378, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-39028315

ABSTRACT

BACKGROUND: Caring for patients with advanced cancer is complex and challenging, requiring varied expertise, including symptom management, communication skills, care coordination and emotional resilience. Within existing literature, the lived experiences of oncology nurses are poorly articulated in countries with a lower income where formal palliative care (PC) is absent. AIM: To explore the lived experiences of Gazan oncology nurses who provide care to patients with advanced cancer in healthcare systems, without formal palliative care infrastructure. METHODS: A phenomenological approach was adopted. Semi-structured interviews were conducted between January and April 2022, in the Turkish Palestinian Friendship Hospital. Thematic analysis used the themes (corporeality, relationality, spatiality and temporality) to facilitate reflection on the meaning of participants' lived experiences. RESULTS: Interviews were undertaken with 16 oncology nurses. The experience of the 'erosion of nurses' work when coping with anxious attachments to patients and families' was the overarching theme in nurses' views, characterised by five sub-themes: (1) inadequacy of PC training and resources, (2) serving humanity, (3) pride in their profession, (4) existential distress and the coping strategies used by nurses, and (5) reported stress and anxiety when caring for seriously ill patients and their families. CONCLUSIONS: The study sheds light on the challenges and powerful emotions experienced by oncology nurses who care for patients with advanced cancer, yet lack the necessary PC training and institutional resources. The findings indicate an urgent need for PC training for nurses within the Gazan healthcare system and other lower-income settings. Assessing nurses' emotions and relationships with patients and family caregivers is imperative to enable optimum care for patients with cancer and to foster resilience among their nurses.


Subject(s)
Neoplasms , Oncology Nursing , Humans , Neoplasms/nursing , Adult , Female , Male , Middle Aged , Palliative Care , Qualitative Research , Adaptation, Psychological , Turkey , Interviews as Topic
14.
Circ Res ; 2024 Jul 03.
Article in English | MEDLINE | ID: mdl-38957990

ABSTRACT

BACKGROUND: PANX1 (pannexin 1), a ubiquitously expressed ATP release membrane channel, has been shown to play a role in inflammation, blood pressure regulation, and myocardial infarction. However, the possible role of PANX1 in cardiomyocytes in the progression of heart failure has not yet been investigated. METHOD: We generated a novel mouse line with constitutive deletion of PANX1 in cardiomyocytes (Panx1MyHC6). RESULTS: PANX1 deletion in cardiomyocytes had no effect on unstressed heart function but increased the glycolytic metabolism and resulting glycolytic ATP production, with a concurrent decrease in oxidative phosphorylation, both in vivo and in vitro. In vitro, treatment of H9c2 cardiomyocytes with isoproterenol led to PANX1-dependent release of ATP and Yo-Pro-1 uptake, as assessed by pharmacological blockade with spironolactone and siRNA-mediated knockdown of PANX1. To investigate nonischemic heart failure and the preceding cardiac hypertrophy, we administered isoproterenol, and we demonstrated that Panx1MyHC6 mice were protected from systolic and diastolic left ventricle volume increases as a result of cardiomyocyte hypertrophy. Moreover, we found that Panx1MyHC6 mice showed decreased isoproterenol-induced recruitment of immune cells (CD45+), particularly neutrophils (CD11b+, Ly6g+), to the myocardium. CONCLUSIONS: Together, these data demonstrate that PANX1 deficiency in cardiomyocytes increases glycolytic metabolism and protects against cardiac hypertrophy in nonischemic heart failure at least in part by reducing immune cell recruitment. Our study implies PANX1 channel inhibition as a therapeutic approach to ameliorate cardiac dysfunction in patients with heart failure.

15.
Orthop Rev (Pavia) ; 16: 120308, 2024.
Article in English | MEDLINE | ID: mdl-38957745

ABSTRACT

The diagnosis of periprosthetic joint infections (PJI) presents a formidable challenge to orthopaedic surgeons due to its complex and diverse manifestations. Accurate diagnosis is of utmost importance, as even mild pain following joint replacement surgery may indicate PJI in the absence of a definitive gold standard diagnostic test. Numerous diagnostic modalities have been suggested in the literature, and international societies have continually updated diagnostic criteria for this debilitating complication. This review article aims to comprehensively examine the latest evidence-based approaches for diagnosing PJI. Through a thorough analysis of current literature, we explore promising diagnostic strategies that have demonstrated effectiveness in identifying PJI. These strategies encompass the utilization of laboratory markers, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), alongside imaging techniques such as magnetic resonance imaging (MRI) and leukocyte scintigraphy. Additionally, we highlight the importance of synovial fluid analysis, including the potential role of alpha-defensin as a biomarker, and examine evolving international diagnostic criteria to standardize and improve diagnostic accuracy.

16.
PLoS Negl Trop Dis ; 18(7): e0012305, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38976758

ABSTRACT

As Wolbachia pipientis is more widely being released into field populations of Aedes aegypti for disease control, the ability to select the appropriate strain for differing environments is increasingly important. A previous study revealed that longer-term quiescence in the egg phase reduced the fertility of mosquitoes, especially those harboring the wAlbB Wolbachia strain. This infertility was also associated with a greater biting rate. Here, we attempt to quantify the effect of this heightened biting behavior on the transmission potential of the dengue virus using a combination of assays for fitness, probing behavior, and vector competence, allowing repeat feeding, and incorporate these effects in a model of R0. We show that Wolbachia-infected infertile mosquitoes are more interested in feeding almost immediately after an initial blood meal relative to wild type and Wolbachia-infected fertile mosquitoes and that these differences continue for up to 8 days over the period we measured. As a result, the infertile Wolbachia mosquitoes have higher virus prevalence and loads than Wolbachia-fertile mosquitoes. We saw limited evidence of Wolbachia-mediated blocking in the disseminated tissue (legs) in terms of prevalence but did see reduced viral loads. Using a previously published estimate of the extrinsic incubation period, we demonstrate that the effect of repeat feeding/infertility is insufficient to overcome the effects of Wolbachia-mediated blocking on R0. These estimates are very conservative, however, and we posit that future studies should empirically measure EIP under a repeat feeding model. Our findings echo previous work where periods of extensive egg quiescence affected the reproductive success of Wolbachia-infected Ae. aegypti. Additionally, we show that increased biting behavior in association with this infertility in Wolbachia-infected mosquitoes may drive greater vector competence. These relationships require further exploration, given their ability to affect the success of field releases of Wolbachia for human disease reduction in drier climates where longer egg quiescence periods are expected.


Subject(s)
Aedes , Dengue Virus , Dengue , Feeding Behavior , Mosquito Vectors , Wolbachia , Aedes/microbiology , Aedes/virology , Aedes/physiology , Animals , Wolbachia/physiology , Dengue Virus/physiology , Mosquito Vectors/microbiology , Mosquito Vectors/virology , Mosquito Vectors/physiology , Dengue/transmission , Female , Viral Load , Ovum/virology , Ovum/microbiology
17.
Heart Rhythm ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39053751

ABSTRACT

BACKGROUND: The declining number of electrophysiologists pursuing academic research careers could negatively impact innovation for patients with heart rhythm disorders in the coming decades. OBJECTIVE: To explore determinants of research engagement after graduation from EP fellowship programs and evaluate associated barriers and opportunities. METHODS: A mixed methods survey of EP fellows and early career electrophysiologists was conducted, drawing from Heart Rhythm Society members. The survey encompassed 20 questions on demographics, research involvement, perceived research barriers, and perspectives on research time and opportunities. Responses were analyzed with robust Poisson regression. RESULTS: Among 259 respondents, those with dedicated research blocks during their fellowship had a significantly higher interest in future research (RR 1.15, p=0.04). The number of peer-reviewed publications modestly influenced interest in continued research (RR 1.0034 per publication, p < 0.0001), but there was no relationship to gender or race. Educational resources, networking opportunities, mentorship, funding, and protected time to enhance research engagement were important themes in the qualitative analysis, while key barriers to post-fellowship research were lack of mentorship, insufficient resources and time constraints in that order, particular with respect to women in research. Notably, no significant differences in barriers were observed between community training programs and academic centers. CONCLUSIONS: Research experience and mentorship during EP fellowship were key determinants of subsequent research success after training, with similar findings by sex and race. These findings explain how fellowship training influences a physician's research practice post training and highlights opportunities to modify EP fellowships and augment research retention.

18.
Neurosurgery ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39041790

ABSTRACT

BACKGROUND AND OBJECTIVE: Ambulatory surgery centers (ASCs) are increasingly common venues for same-day neurosurgical procedures, allowing for cost-effective, high-quality patient care. We present the first and largest series of patients undergoing diagnostic cerebral angiography at an ASC to demonstrate the effectiveness, safety, and efficiency of outpatient endovascular care. METHODS: We retrospectively reviewed data for consecutive patients who underwent diagnostic cerebral angiography at our ASC between January 1, 2024, and May 29, 2024. Data collected included vascular access approach, procedural duration, turnover time, and periprocedural complications. Using a standardized 2-week postprocedural survey, patients were asked to provide comments and rate their subjective satisfaction from a 1 to 5 scale, with "5" being completely satisfied. All cases were performed with a physician team comprising 1 attending neuroendovascular neurosurgery and 1 neuroendovascular fellow present. Fentanyl and midazolam were administered for conscious sedation in all cases. RESULTS: Among the 67 patients included in this series, the mean procedural duration was 29.4 ± 8.6 minutes. The mean turnover time was 13.7 ± 3.6 minutes. Between transradial (46 of 67 [68.7%]) and transfemoral (21 of 67 [31.3%]) access site approaches, there were no statistically significant differences in mean procedural duration (29.4 ± 8.0 vs 29.2 ± 9.9 minutes, respectively; P = .72) or turnover time (14.0 ± 3.9 vs 12.9 ± 2.8 minutes, respectively; P = .4). No complications occurred periprocedurally or within the 2-week follow-up period. A total of 48 (71.6%) of 67 patients responded to the postprocedural survey, all of whom unanimously reported a score of "5." CONCLUSION: We found that diagnostic cerebral angiography performed at our ASC was safe and effective for patient care. In addition, all survey respondents (71.6% of those provided the survey) reported highest levels of satisfaction. The integration of neuroendovascular procedures into ASCs potentially offers a cost-effective and highly efficient option in an evolving economic landscape.

19.
Dalton Trans ; 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39041824

ABSTRACT

Nominally, meso-hydroxyoxochlorins, like known 5-hydroxy-7-oxo-octaethylchlorin (9), its nickel complex [5-hydroxy-7-oxo-octaethylchlorinato]nickel(II) (9Ni), or the novel 5-hydroxy-7,17-dioxo-octaethylbacteriochlorin (10), incorporate an acetylacetonate (acac)-moiety in the enol form in their chromophore structures. X-Ray diffraction studies of the compounds show the presence of a strong H-bond between the enol and flanking ß-ketone. Like acac, the functionality can be deprotonated. However, unlike regular acac-like moieties, we did not find any indication that this functionality is competent in chelating any of the 3d or 4d transition metal ions tested. Evidently, the conjugation that contributes to the stability of acac as a ligand cannot be expressed in the meso-hydroxyoxochlorins since it would perturb the aromaticity of the porphyrinic chromophores; in other words, the metal binding energies do not offset the loss in aromaticity. The halochromic properties of the molecules provide some more insight into the location of the protonation/deprotonation sites. The interpretation of the findings is supported by computations.

20.
ACS Catal ; 14(13): 9678-9686, 2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38988654

ABSTRACT

Leaching behavior of three different Pd heterogeneous catalysts (PdEnCat 30, FibreCat FC1001, and Pd/Al2O3) during the Heck reaction of iodobenzene and methyl acrylate, in the presence of triethylamine, was compared using a tandem flow reactor. While leaching was observed in all three cases, Pd/Al2O3 appeared to be the most robust, showing little/no leaching at ambient temperature. The leached Pd species also appear to display different catalytic activities. With a slight modification of the reactor, the leaching caused by individual components of the reaction mixture can be assessed separately. For the polymer-supported catalysts, triethylamine caused the largest amount of leaching, even at 30 °C. In contrast, the leaching from Pd/Al2O3 was observed only in the presence of iodobenzene at 90 °C. Variations in leaching behavior were ascribed to differences in Pd species and immobilization methods.

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