Relativity as a Synthesis Design Principle: A Comparative Study of [3 + 2] Cycloaddition of Technetium(VII) and Rhenium(VII) Trioxo Complexes with Olefins.

The difference in [3 + 2] cycloaddition reactivity between fac-[MO3(tacn)]+ (M = Re, 99Tc; tacn = 1,4,7-triazacyclononane) complexes has been reexamined with a selection of unsaturated substrates including sodium 4-vinylbenzenesulfonate, norbornene, 2-butyne, and 2-methyl-3-butyn-2-ol (2MByOH). None of the substrates was found to react with the Re cation in water at room temperature, whereas the 99Tc reagent cleanly yielded the [3 + 2] cycloadducts. Interestingly, a bis-adduct was obtained as the sole product for 2MByOH, reflecting the high reactivity of a 99TcO-enediolato monoadduct. On the basis of scalar relativistic and nonrelativistic density functional theory calculations of the reaction pathways, the dramatic difference in reactivity between the two metals has now been substantially attributed to differences in relativistic effects, which are much larger for the 5d metal. Furthermore, scalar-relativistic ΔG values were found to decrease along the series propene > norbornene > 2-butyne > dimethylketene, indicating major variations in the thermodynamic driving force as a function of the unsaturated substrate. The suggestion is made that scalar-relativistic effects, consisting of greater destabilization of the valence electrons of the 5d elements compared with those of the 4d elements, be viewed as a new design principle for novel 99mTc/Re radiopharmaceuticals, as well as more generally in heavy-element coordination chemistry.

Bis-Arene Complexes [Re(η6-arene)2]+ as Highly Stable Bioorganometallic Scaffolds.

The synthesis of mono- and difunctionalized [Re(η6-C6H5R)(η6-C6H6-nRn)]+ (n = 0, 1; R = COOH, Br) complexes starting from [Re(η6-benzene)2]+ is described. The lithiation of [Re(η6-benzene)2]+ with n-BuLi leads preferentially to the neutral, alkylated product [Re(η6-C6H6)(η5-C6H6-Bu)] but not to the expected deprotonation of the arene ring. Deprotonation/lithiation with LDA gave the mono- and the dilithiated products in situ. Their reactions with 1,1,2,2-tetra-bromoethane (TBE) or with CO2, respectively, gave [Re(η6-C6H5Br)(η6-C6H6)]+, [Re(η6-C6H5Br)2]+, or [Re(η6-C6H5COOH)(η6-C6H6)]+, [Re(η6-C6H5COOH)2]+. These functionalized derivatives of [Re(η6-benzene)2]+ represent novel precursors for the synthesis of bioconjugates to bioactive structures, comparable to [Co(Cp)2]+ or [Fe(Cp)2]. Different model compounds [Re(η6-C6H5R)(η6-C6H6-nRn)]+ (n = 0, 1; R = -SCH2Ph, -NHPh, -CONHCH2Ph, -C6H5-COdpa) were synthesized via amide bond formation and nucleophilic aromatic substitution. These conjugates were fully characterized including X-ray structure analyses of most products. For all complexes, the 1H NMR arene proton signals are strongly upfield-shifted as compared to those of the noncoordinated arenes. The electrochemical analyses show an irreversible, probably substituent-centered oxidation, which contrasts the cyclic voltammetry of the underivatized complexes where oxidation is fully reversible. The stability of the core and the reactivity of the substituents make these bis-arene complexes useful precursors in medicinal inorganic chemistry, comparable to cobaltocenium or ferrocene.

Toward organometallic (99m)Tc imaging agents: synthesis of water-stable (99)Tc-NHC complexes.

(99)Tc(V)O2-NHC complexes containing monodentate and bidentate N-heterocyclic carbenes (NHCs) have been prepared by the reactions of [TcO(glyc)2](-) (glyc = ethyleneglycolato) with 1,3-dimethylimidazoline-2-ylidene (L1), 1,1'-methylene-3,3'-dimethyl-4,4'-diimidazoline-2,2'-diylidene (L2), and 1,1'-methylene-3,3'-diethyl-4,4'-diimidazoline-2,2'-diylidene (L3) in THF. The resulting complexes were fully characterized and their stabilities investigated. While complexes with monodentate NHCs only are hydrolytically unstable, complexes containing bidentate NHCs are water-stable over a broad pH range. The high water stability allows interconversion of the {(99)Tc(V)O2}(+) core into {(99)Tc(V)OCl}(2+) with HCl as the H(+) and Cl(-) source. An alternative procedure to obtain (99)Tc(V)O2-NHC complexes is the in situ deprotonation of imidazolium salts, enabling the preparation of (99)Tc(V)O2-NHC compounds without free NHCs, thus increasing the scope of NHC ligands drastically. The remarkable stability and pH-controllable reactivity of the new complexes underlines the potential of NHCs as stabilizing ligands for (99)Tc complexes and paves the way for the first (99m)Tc-NHC complexes in the future.

Comparison of efficacy and safety of intracoronary sodium nitroprusside and intravenous adenosine for assessing fractional flow reserve.

OBJECTIVES: The purpose of this study was to compare the efficacy and safety of intracoronary (IC) nitroprusside and intravenous adenosine (IVA) for assessing fractional flow reserve (FFR). BACKGROUND: IV infusion of adenosine is a standard method to achieve a coronary hyperemia for FFR measurement. However, adenosine is expensive, causes multiple side effects, and is contraindicated in patients with reactive airway disease. Sodium nitroprusside (NTP) is a strong coronary vasodilator but its efficacy and safety for assessing FFR is not well established. METHODS: We compared FFR response and side effects profile of IC NTP and IVA. Bolus of NTP at a dose of 100 µg and IVA (140 µg/kg/min) were used to achieve coronary hyperemia. RESULTS: We evaluated 75 lesions in 53 patients (60% male) mean age 61.6 ± 13.9 years. Mean FFR after NTP was similar to FFR after adenosine (0.836 ± 0.107 vs. 0.856 ± 0.106; P = 0.26; r = 0.91, P < 0.001). NTP induced maximal stable hyperemia within 10 sec (mean: 6.4 ± 1) which lasted consistently between 38 and 60 sec (mean 51 ± 7.5). NTP caused significant (14%), but asymptomatic decrease in mean blood pressure which returned to baseline within 60 sec. Adenosine caused shortness of breath in 26%, headache and flushing in 19%, and transient second degree heart block in 6% of patients. No adverse symptoms were reported after NTP. CONCLUSIONS: IC NTP is as effective as IVA for measuring FFR. NTP is better tolerated by patients. Since NTP is inexpensive, readily available, well tolerated, and safe, it may be a better choice for FFR assessment.

The Use of AngioVac in a Patient With Severe Infective Endocarditis Where Open Heart Surgery Is Contraindicated: A Case Report.

Infectious endocarditis of the tricuspid valve (TV) is a common complication of intravenous (IV) drug use. Endocarditis caused by viridans streptococci can lead to heart valve vegetations, which may be life-threatening due to the potential for embolism and obstruction. The management of large valvular vegetations is often difficult due to the risks involved with open heart surgery, especially in patients with comorbid conditions. The AngioVac device (AngioDynamics Inc., Latham, NY) has been shown in rare cases to be effective at debulking vegetations without the need for invasive surgery. We present a 45-year-old male with a history of intravenous heroin use disorder, hepatitis C, spinal abscesses, and chronic anemia who experienced worsening shortness of breath, generalized weakness, bilateral lower extremity edema, dysuria with dark urine, and blood on toilet paper. Workup revealed a 4.39 × 4.35 cm tricuspid valve vegetation, severe tricuspid regurgitation (TR), acute renal failure, acute on chronic anemia, and thrombocytopenia from sepsis-induced disseminated intravascular coagulation (DIC). AngioVac was used to aspirate the vegetation and effectively reduced the size to 3.75 × 2.31 cm. Follow-up blood cultures revealed no growth after five days. This is the largest documented tricuspid valve vegetation with a successful implementation of the AngioVac to date. This therapy, in conjunction with intravenous antibiotics and hemodialysis, successfully sterilized the vegetation, prevented worsening presentation, and averted life-threatening complications, although severe tricuspid regurgitation persisted. Based on the findings of this case, the AngioVac device is a safe and effective treatment option for tricuspid valve endocarditis patients with large vegetation and severe comorbidities, which contraindicate open heart surgery.

Staged Versus Concomitant Carotid Endarterectomy and Aortic Valve Replacement: A Case Report and Literature Review.

Stroke is a common complication of cardiac surgery, and carotid artery stenosis is an established risk factor for stroke. Therefore, patients with carotid artery stenosis who are undergoing cardiac surgery require proper management of the former either simultaneously or before cardiac surgery. We present a challenging case of a 67-year-old male patient who presented with generalized weakness, severe aortic stenosis, and significant bilateral carotid artery stenosis. The coexistence of these findings sparked a debate about whether to perform a carotid endarterectomy first or an aortic valve replacement. Moreover, a past history of percutaneous coronary intervention and coronary artery bypass grafts made the decision more challenging. Multiple approaches have been employed for the management of coexisting carotid artery stenosis with cardiac surgery; however, no definitive guidelines exist, especially for surgeries other than coronary artery bypass grafts or where the carotid stenosis is bilateral and severe.

Combining bifunctional chelator with (3 + 2)-cycloaddition approaches: synthesis of dual-function technetium complexes.

A new concept for the synthesis of dual-functionalized technetium (Tc) compounds is presented, on the basis of the reactivity of fac-{Tc(VII)O(3)}(+) complexes. The concept combines the "classical" bifunctional chelator (BFC) approach with the new ligand centered labeling strategy of fac-{TcO(3)}(+) complexes with alkenes ((3 + 2)-cycloaddition approach). To evidence this concept, fac-{(99)TcO(3)}(+) model complexes containing functionalized 1,4,7-triazacyclononane (tacn) derivatives N-benzyl-2-(1,4,7-triazonan-1-yl)acetamide (tacn-ba) and 2,2',2″-(1,4,7-triazonane-1,4,7-triyl)triacetic acid (nota·3H) were synthesized and characterized. Whereas [(99)TcO(3)(tacn-ba)](+) [2](+) can be synthesized following a established oxidation procedure starting from the Tc(V) complex [(99)TcO(glyc)(tacn-ba)](+) [1](+), a new synthetic pathway for the synthesis of [(99)TcO(3)(nota)](2-) [5](2-) had to be developed, starting from [(99)Tc(nota·3H)(CO)(3)](+) [4](+) and using sodium perborate tetrahydrate (NaBO(3)·4H(2)O) as oxidizing reagent. While [(99)TcO(3)(nota)](2-) [5](2-) is a very attractive candidate for the development of trisubstituted novel multifunctional radioprobes, (3 + 2)-cycloaddition reactions of [(99)TcO(3)(tacn-ba)](+) [2](+) with 4-vinylbenzenesulfonate (styrene-SO(3)(-)) demonstrated the suitability of monosubstituted tacn derivatives for the new mixed "BFC-(3 + 2)-cycloaddition" approach. Kinetic studies of this reaction lead to the conclusion that the alteration of the electronic structure of the nitrogen donors by, e.g., alkylation can be used to tune the rate of the (3 + 2)-cycloaddition.

Post-cardiac Injury Syndrome Following Permanent Dual-Chamber Pacemaker Implantation.

Post-cardiac injury syndrome is a heterogeneous group of conditions that result from autoimmune-mediated inflammation of the pericardium, epicardium, and myocardium. Interventions such as pacemaker lead insertions, percutaneous coronary interventions, radiofrequency ablations, cardiac surgeries, and Swan-Ganz catheterizations can cause myocardial injury leading to post-traumatic pericarditis. This phenomenon can lead to chest pain, recurrent effusions, and fever along with possible complications of heart failure, arrhythmias, conduction abnormalities as well as cardiac tamponade. Herein, we present a case report of a 64-year-old female with a history of sick sinus syndrome managed with a dual-chamber pacemaker who presented with post-cardiac injury syndrome after three months of pacemaker implantation. She developed a recurrent syndrome of fever, chest discomfort, tachycardia with weakness, hemodynamic instability, hemorrhagic serositis, and cardiac tamponade. The mechanism of exudative inflammatory effusions initially remained inconclusive, as the workup for infectious and malignant processes was negative. However, post-cardiac injury syndrome akin to the Dressler syndrome related to screw-in dual-chamber pacemaker implantation remained a possibility. Her condition was acutely managed with a combination of colchicine and glucocorticoid therapy. She was placed on long-term aspirin and colchicine therapy to prevent any recurrences. This article illustrates a case of post-cardiac injury syndrome after dual-chamber pacemaker implantation, including details of evaluation, management, complications and monitoring of patient progress.

Sibutramine-Induced Nonischemic Cardiomyopathy.

Within the past 20 years, the global pandemic of obesity and associated life-threatening comorbidities significantly promoted the development and intervention of anti-obesity pharmacotherapy. Sibutramine hydrochloride monohydrate, formerly sold under the brand name Meridia and Reductil among others, is an anti-obesity, selective serotonin, and norepinephrine reuptake inhibitor drug that suppresses appetite and reduces body weight in conjunction with lifestyle modifications. However, since 2010, it has been discontinued in a majority of countries such as the United States and European Union due to an associated increase in cardiovascular events such as hypertension, tachycardia, arrhythmias, and myocardial infarction. Thus, this article illustrates a case of sibutramine-induced nonischemic cardiomyopathy, including details of evaluation, management, and monitoring of patient progress. Herein, we present a case report of a 19-year-old male with no prior medical conditions who presented to the emergency department after being found in a state of cardiac arrest (pulseless ventricular fibrillation) with consequent intubation in the field. Upon admission, cardiac catheterization and echocardiography revealed patent coronary arteries with a reduced ejection fraction of approximately 15%-20%. Acute systolic heart failure secondary to nonischemic cardiomyopathy was treated with standard medical management. In addition, due to continued episodes of non-sustained ventricular tachycardia, the patient also underwent a subcutaneous implantable cardioverter-defibrillator (ICD) placement.

Esophageal perforation, the most feared complication of TEE: early recognition by multimodality imaging.

Esophageal perforation is the most feared complication of transesophageal echocardiography (TEE), although the overall risk is extremely low. We report a case of esophageal perforation in a 77-year-old woman who had no apparent contraindications to TEE. Chronic steroid therapy for symptoms of asthma as well as osteophytic changes of the cervical vertebrae contributed to her increased risk of perforation. Unlike in prior reports, the perforation in this case was fortuitously recognized rapidly due to ingestion of a carbonated beverage for evaluation of a hiatal hernia suspected during a subsequent transthoracic echocardiogram performed because of inadequate TEE images after a difficult intubation. The incidence of esophageal perforation in our series (1 in 5,000 TEEs, 0.02%) is similar to that reported in the literature. Early recognition and prompt surgical repair of the esophageal perforation led to favorable outcome in our patient.

Assessment and management of a 1.77-cm2 mitral leaflet perforation as a subclinical cause of mitral regurgitation.

Anterior mitral valve perforations are commonly due to underlying infective endocarditis, which can lead to significant mitral valve insufficiency. In these cases, clinicians should have a high index of suspicion for infective endocarditis. After appropriate imaging, immediate surgical intervention is unequivocally the choice of management here for optimal patient outcomes.

From TcVII to TcI; facile syntheses of bis-arene complexes [99(m)Tc(arene)2]+ from pertechnetate.

Bis-arene complexes of technetium represent a fundamental class of organometallic compounds. Due to complex synthetic routes, no detailed insights into their properties have been reported so far. Reacting [99TcO4]- with arenes in the exclusive presence of AlCl3 gives highly stable [99Tc(arene)2]+ in good yields. These complexes have extraordinarily high stabilities, where oxidation is found to occur at potentials higher than +1.3 V and reduction at potentials below -2 V vs. Fc/Fc+. The 99mTc analogues are similarly synthesised by applying a novel ionic liquid extraction pathway. Complexes of 99mTc with suitably functionalized arenes will represent new building blocks for bioorganometallic pharmaceuticals in molecular imaging.

Activation of [(99(m))TcO4](-) by phosphonium cations.

Phosphonium salts in solution or bound to solid phase supports interact with the robust [(99(m))TcO4](-) anion in neutral water. This activated form of [(99(m))TcO4](-) represents a source for complexes with the fac-{(99m)Tc(VII)O3}(+) core, which can be synthesized in high yields and purity.

Evaluating a dynamic process model of wellbeing for parents of children with disabilities: a multi-method analysis.

PURPOSE: The purpose of this study was to evaluate possible determinants of parent wellbeing using a contextual model of parent adjustment. METHOD: One hundred forty parents of children with various disabilities (i.e., autism, intellectual disabilities, and other health impairments) participated in this investigation. Parents completed a survey consisting of basic demographic characteristics of the parent, child-disability characteristics, parent problem solving ability, access to information and resources, environmental/social supports, appraisals of threat and growth, and measures of life satisfaction and physical/mental health. Structural equation modeling was conducted to test a hypothesized contextual model of parent wellbeing. RESULTS: Results indicated strong fit to the a priori model. After controlling for the contribution of parent demographic variables, the largest contributors to the prediction of parent wellbeing were parent problem solving ability, access to resources, environmental/social supports, and parent appraisals of threat. Child functional impairment was not significantly associated with parent wellbeing. CONCLUSIONS: Access to resources and environmental/social supports have a greater direct effect on parent wellbeing than parent and child demographic variables and disability severity. Threat appraisals have direct and mediating effects on parent wellbeing. Implications related to the importance of resources and environmental/social supports, appraisals of threat and growth, and problem solving abilities on the wellbeing of parents of children with disabilities are discussed.

Depression among parents of children with disabilities.

We examined the rate of depression among 110 parents of children with disabilities and tested a model to determine the unique factors associated with parental depression. Consenting parents completed measures of depression, family satisfaction, physical health, problem-solving abilities, stress appraisals, and child functional impairment. Participants were categorized as depressed or nondepressed based on their responses to the Patient Health Questionnaire (PHQ9; Kroenke, Spitzer, & Williams, 2001). Nineteen percent of the parents met screening criteria for depression. Regression analyses revealed that threat appraisals, poorer physical health, and lower family satisfaction were uniquely associated with depression status with 83.3% accuracy. These findings highlight the importance of family satisfaction, problem solving ability, physical health, and the influence of appraisal processes on depression among parents of children with disabilities.

National prevalence rates of bully victimization among students with disabilities in the United States.

This study examined the prevalence rates of bully victimization and risk for repeated victimization among students with disabilities using the Special Education Elementary Longitudinal Study and the National Longitudinal Transition Study-2 longitudinal datasets. Results revealed that a prevalence rate ranging from 24.5% in elementary school to 34.1% in middle school. This is one to one and a half times the national average for students without disabilities. The rate of bully victimization was highest for students with emotional disturbance across school levels. Findings from this study also indicated that students with disabilities who were bullied once were at high risk of being bullied repeatedly. Elementary and middle school students with autism and high school students with orthopedic impairments were at the greatest risk of experiencing repeated victimization. Implications of the findings are discussed.

Giving parents a voice: A qualitative study of the challenges experienced by parents of children with disabilities.

BACKGROUND: This study sought to examine the specific sources of challenges as identified by parents of children with disabilities. METHOD: Focus groups were conducted with 40 parent caregivers. Data gathered were coded into themes which were then analyzed through an intentional process of data reduction that resulted in the cross site validation of four superordinate themes. RESULTS: Four themes emerged as the most prominent barriers to positive parent wellbeing: (a) access to information and services, (b) financial barriers, (c) school and community inclusion, and (d) family support. These four themes are indicative of problems associated with a lack of match between caregiver needs and services, resources, or support available in the community to meet those needs. CONCLUSION: Caring for a child with a disability can be challenging, but many of these challenges are likely due to a lack of necessary environmental supports. Future research should expand on these findings and policy makers, scientists and providers should give particular attention to the environmental support needs of parents in order to create policies and interventions that are more family-centered.

Right coronary artery anatomical variants: where and how?

BACKGROUND: Ectopic origin of the right coronary artery (RCA) occurs in approximately 1.0% of studied populations. We investigated the prevalence and location of ectopic RCAs among patients undergoing coronary angiography (CA) and assessed its effects on resource utilization. METHODS: Cases of ectopic RCAs were prospectively collected over 21 months among patients undergoing cardiac catheterization at a University Hospital. "Ectopic RCA" was defined as a RCA originating outside the posterior two-thirds of the right coronary sinus. RESULTS: The study population included 2,120 patients, of which 23 (1.1%) had ectopic RCAs. Of these, 15 (65%) originated from the anterior third of the right sinus, while 8 (35%) originated from the anterior half of the left sinus. Mean procedure and fluoroscopy times were 60 +/- 33 and 15 +/- 12 minutes (min) for the former, and 78 +/- 35 and 31 +/- 20 min for the latter, while mean contrast volume for CA was 112 +/- 62 ml and 192 +/- 85 ml, respectively. 26% required a second CA or a second intervention to image the RCA. CONCLUSION: Ectopic RCAs pose a clinical problem, consuming time and resources. The search for an ectopic RCA should have < 90 degree boundaries limited to the anterior third of the right sinus and anterior half of the left sinus.

QT dispersion as a predictor for arrhythmias in patients with acute ST elevation myocardial infarction.

AIMS AND OBJECTIVES: To study the effect of Heart Rate Variability (HRV) and QT dispersion (QTd) in patients presenting with Acute ST elevation myocardial infarction (STEMI). METHODS: This is a retrospective study conducted on patients admitted with the diagnosis of acute ST elevation myocardial infarction. In all 100 patients with acute myocardial infarction in one year were subjected to a complete evaluation in terms of history and examination. Besides routine investigations standard 12 lead ECG was evaluated in all cases on admission, after 4 hrs, 24 hrs, 48 hrs and on discharge. RESULTS: The most common presenting symptoms were chest pain (88%) and dyspnea (50%). Tachycardia was seen in 56% while congestive heart failure was present in 29% patients. Patients who died had a higher QTd in comparison to patients who survived. CONCLUSIONS: Markers of autonomic regulation of heart like QTd provides valuable information about the future course of events in a patient following acute STEMI which can be utilized to plan the future course of management in patients especially predisposed to adverse and catastrophic outcomes.