Functional significance of recruitable collaterals during temporary coronary occlusion evaluated by 99mTc-sestamibi single-photon emission computerized tomography

AbstractOBJECTIVESThe present study evaluated the impact of recruitable collaterals on regional myocardial perfusion measured by 99mtechnetium (Tc)-sestamibi single-photon emission computerized tomography (SPECT) during temporary coronary occlusion and related these estimates to the coronary wedge pressure and electrocardiographic (ECG) ST-segment changes.BACKGROUNDClinical variables (angina and ECG changes) and intracoronary flow and pressure recordings have indicated a protective role of recruitable collaterals on myocardial perfusion during percutaneous transluminal coronary angioplasty (PTCA).METHODSThirty patients (mean age 55 years, SD 9; 20 men) with stable angina pectoris and proximal nonoccluding single-vessel left anterior descending coronary artery (LAD)-stenosis scheduled for PTCA were included. Visualization of recruitable collaterals by ipsilateral and contralateral contrast injection, registration of coronary wedge pressure and injection of 99mTc-sestamibi during 90-s LAD occlusions were undertaken. A rest perfusion study was performed within four days before PTCA. As an estimate of the severity of regional hypoperfusion during occlusion, an occlusion/rest count ratio was calculated (mean defect pixel count during occlusion divided by mean pixel count in identical regions at rest).RESULTSThe scintigraphic occlusion/rest count ratio was higher in patients with recruitable collaterals (n = 16), 67 ± 11%, compared to patients without collaterals (n = 14), 60 ± 6% (p < 0.05). The occlusion/rest count ratio correlated with the coronary wedge pressure (R2= 0.34; p < 0.001). The occlusion/rest count ratio was lower, 61 ± 6%, in patients with ST-segment elevation (n = 23) versus 74 ± 9% in patients without ST-segment elevation (n = 7) (p < 0.0001).CONCLUSIONSUsing 99mTc-sestamibi SPECT imaging during brief episodes of coronary occlusion, the severity of regional myocardial hypoperfusion was reduced by the presence of recruitable collaterals in a selected patient population with proximal LAD stenoses. Our results demonstrate a protective effect of recruitable collaterals on myocardial perfusion during temporary coronary occlusion

Mdm38 interacts with ribosomes and is a component of the mitochondrial protein export machinery

Saccharomyces cerevisiae Mdm38 and Ylh47 are homologues of human Letm1, a protein implicated in Wolf-Hirschhorn syndrome. We analyzed the function of Mdm38 and Ylh47 in yeast mitochondria to gain insight into the role of Letm1. We find that mdm38Δ mitochondria have reduced amounts of certain mitochondrially encoded proteins and low levels of complex III and IV and accumulate unassembled Atp6 of complex V of the respiratory chain. Mdm38 is especially required for efficient transport of Atp6 and cytochrome b across the inner membrane, whereas Ylh47 plays a minor role in this process. Both Mdm38 and Ylh47 form stable complexes with mitochondrial ribosomes, similar to what has been reported for Oxa1, a central component of the mitochondrial export machinery. Our results indicate that Mdm38 functions as a component of an Oxa1-independent insertion machinery in the inner membrane and that Mdm38 plays a critical role in the biogenesis of the respiratory chain by coupling ribosome function to protein transport across the inner membrane

The translocator maintenance protein Tam41 is required for mitochondrial cardiolipin biosynthesis

The mitochondrial inner membrane contains different translocator systems for the import of presequence-carrying proteins and carrier proteins. The translocator assembly and maintenance protein 41 (Tam41/mitochondrial matrix protein 37) was identified as a new member of the mitochondrial protein translocator systems by its role in maintaining the integrity and activity of the presequence translocase of the inner membrane (TIM23 complex). Here we demonstrate that the assembly of proteins imported by the carrier translocase, TIM22 complex, is even more strongly affected by the lack of Tam41. Moreover, respiratory chain supercomplexes and the inner membrane potential are impaired by lack of Tam41. The phenotype of Tam41-deficient mitochondria thus resembles that of mitochondria lacking cardiolipin. Indeed, we found that Tam41 is required for the biosynthesis of the dimeric phospholipid cardiolipin. The pleiotropic effects of the translocator maintenance protein on preprotein import and respiratory chain can be attributed to its role in biosynthesis of mitochondrial cardiolipin

Elementary Classroom Teachers’ Self-Reported Use of Movement Integration Products and Perceived Facilitators and Barriers Related to Product Use

Movement integration (MI) products are designed to provide children with physical activity during general education classroom time. The purpose of this study was to examine elementary classroom teachers’ self-reported use of MI products and subsequent perceptions of the facilitators of and barriers to MI product use. This study utilized a mixed-methods design. Elementary classroom teachers (n = 40) at four schools each tested four of six common MI products in their classroom for one week. Teachers completed a daily diary, documenting duration and frequency of product use. Following each product test, focus groups were conducted with teachers to assess facilitators and barriers. MI product use lasted for 11.2 (Standard Deviation (SD) = 7.5) min/occasion and MI products were used 4.1 (SD = 3.5) times/week on average. Activity Bursts in the Classroom for Fitness, GoNoodle, and Physical Activity Across the Curriculum were most frequently used. Facilitators of and barriers to MI product use were identified within three central areas—logistics, alignment with teaching goals, and student needs and interests. Teachers were receptive to MI products and used them frequently throughout the week. When considering the adoption of MI products, teachers, administrators, and policy makers should consider products that are readily usable, align with teaching goals, and are consistent with student needs and interests

Pharmacokinetics of the phosphatidylserine tracers 99m Tc-lactadherin and 99m Tc-annexin V in pigs

Abstract Background: Phosphatidylserine (PS) is a phospholipid normally located in the inner leaflet of the cell membrane. PS is translocated from the inner to the outer leaflet of the plasma membrane during the early stages of apoptosis and in necrosis. In cell and animal studies, reversible PS externalisation to the outer membrane leaflet has been observed in viable cells. Hence, PS markers have been proposed as markers of both reversibly and irreversibly damaged cells. The purpose of this experimental study in pigs was to investigate the kinetics of the newly introduced PS marker technetium-99m-labelled lactadherin ( 99m Tc-lactadherin) in comparison with the well-known PS trace

Neuronal Redox-Imbalance in Rett Syndrome Affects Mitochondria as Well as Cytosol, and Is Accompanied by Intensified Mitochondrial O2 Consumption and ROS Release

Rett syndrome (RTT), an X chromosome-linked neurodevelopmental disorder affecting almost exclusively females, is associated with various mitochondrial alterations. Mitochondria are swollen, show altered respiratory rates, and their inner membrane is leaking protons. To advance the understanding of these disturbances and clarify their link to redox impairment and oxidative stress, we assessed mitochondrial respiration in defined brain regions and cardiac tissue of male wildtype (WT) and MeCP2-deficient (Mecp2-/y) mice. Also, we quantified for the first time neuronal redox-balance with subcellular resolution in cytosol and mitochondrial matrix. Quantitative roGFP1 redox imaging revealed more oxidized conditions in the cytosol of Mecp2-/y hippocampal neurons than in WT neurons. Furthermore, cytosol and mitochondria of Mecp2-/y neurons showed exaggerated redox-responses to hypoxia and cell-endogenous reactive oxygen species (ROS) formation. Biochemical analyzes exclude disease-related increases in mitochondrial mass in Mecp2-/y hippocampus and cortex. Protein levels of complex I core constituents were slightly lower in Mecp2-/y hippocampus and cortex than in WT; those of complex V were lower in Mecp2-/y cortex. Respiratory supercomplex-formation did not differ among genotypes. Yet, supplied with the complex II substrate succinate, mitochondria of Mecp2-/y cortex and hippocampus consumed more O2 than WT. Furthermore, mitochondria from Mecp2-/y hippocampus and cortex mediated an enhanced oxidative burden. In conclusion, we further advanced the molecular understanding of mitochondrial dysfunction in RTT. Intensified mitochondrial O2 consumption, increased mitochondrial ROS generation and disturbed redox balance in mitochondria and cytosol may represent a causal chain, which provokes dysregulated proteins, oxidative tissue damage, and contributes to neuronal network dysfunction in RTT

Actionable Patient Safety Solutions (APSS) #6: Hand-off Communications

Hand-off communications, or hand-off processes, involve the transition of care as well as the transfer of patient-specific information by one healthcare professional to another with the purpose of providing a patient with safe, continuous care. A successful hand-off can only be achieved by effective communication

Loss of Mitochondrial Ca ²⁺ Uniporter Limits Inotropic Reserve and Provides Trigger and Substrate for Arrhythmias in Barth Syndrome Cardiomyopathy

Background: Barth syndrome (BTHS) is caused by mutations of the gene encoding tafazzin, which catalyzes maturation of mitochondrial cardiolipin and often manifests with systolic dysfunction during early infancy. Beyond the first months of life, BTHS cardiomyopathy typically transitions to a phenotype of diastolic dysfunction with preserved ejection fraction, blunted contractile reserve during exercise, and arrhythmic vulnerability. Previous studies traced BTHS cardiomyopathy to mitochondrial formation of reactive oxygen species (ROS). Because mitochondrial function and ROS formation are regulated by excitation-contraction coupling, integrated analysis of mechano-energetic coupling is required to delineate the pathomechanisms of BTHS cardiomyopathy. Methods: We analyzed cardiac function and structure in a mouse model with global knockdown of tafazzin ( Taz -KD) compared with wild-type littermates. Respiratory chain assembly and function, ROS emission, and Ca 2+ uptake were determined in isolated mitochondria. Excitation-contraction coupling was integrated with mitochondrial redox state, ROS, and Ca 2+ uptake in isolated, unloaded or preloaded cardiac myocytes, and cardiac hemodynamics analyzed in vivo. Results: Taz -KD mice develop heart failure with preserved ejection fraction (>50%) and age-dependent progression of diastolic dysfunction in the absence of fibrosis. Increased myofilament Ca 2+ affinity and slowed cross-bridge cycling caused diastolic dysfunction, in part, compensated by accelerated diastolic Ca 2+ decay through preactivated sarcoplasmic reticulum Ca 2 + -ATPase. Taz deficiency provoked heart-specific loss of mitochondrial Ca 2+ uniporter protein that prevented Ca 2+ -induced activation of the Krebs cycle during β-adrenergic stimulation, oxidizing pyridine nucleotides and triggering arrhythmias in cardiac myocytes. In vivo, Taz -KD mice displayed prolonged QRS duration as a substrate for arrhythmias, and a lack of inotropic response to β-adrenergic stimulation. Cellular arrhythmias and QRS prolongation, but not the defective inotropic reserve, were restored by inhibiting Ca 2+ export through the mitochondrial Na + /Ca 2+ exchanger. All alterations occurred in the absence of excess mitochondrial ROS in vitro or in vivo. Conclusions: Downregulation of mitochondrial Ca 2+ uniporter, increased myofilament Ca 2+ affinity, and preactivated sarcoplasmic reticulum Ca 2+ -ATPase provoke mechano-energetic uncoupling that explains diastolic dysfunction and the lack of inotropic reserve in BTHS cardiomyopathy. Furthermore, defective mitochondrial Ca 2+ uptake provides a trigger and a substrate for ventricular arrhythmias. These insights can guide the ongoing search for a cure of this orphaned disease

Bacterial infections among patients with psychiatric disorders: Relation with hospital stay, age, and psychiatric diagnoses.

The prevalence of infections is supposed to be higher in older patients and to extend the length of hospital stays. This study aimed, first, to test this supposition within a large psychiatric population which we divided into four clusters of psychiatric ICD-10 diagnoses: F00-F03 (dementias), F10 (substance disorders), F20-29 (schizophrenia, schizophreniform and other non-mood psychotic disorders), F32-F33 (major depressive disorders). Second, despite the increasing evidence for the role of infections in psychiatric disorders, it is, to the best of our knowledge, largely unknown whether the rates of infections with pathogens of the four most frequent germ families differ between psychiatric diseases. Thus, in a retrospective study, the results of clinical routine examinations (pap smear, analysis of midstream urine, stool) dependent on symptoms in 8545 patients of a German psychiatric clinic were analyzed in a 12-year dataset. Results show that a longer hospital stay was associated with an increased number of microbiological tests, but led to no significant difference between positive vs. negative findings. Consistent with previous studies, patients with infections were older than patients without infections. For the F10 diagnosis cluster we found a significantly reduced (F10: Staphylococcaceae) and for the F20-29 cluster a heightened risk of infections (Staphylococcaceae, Corynebacteriaceae). Furthermore, patients belonging to the F00-F03 cluster exhibited elevated rates of infections with all four germ families. The latter can be ascribed to patients' age as we found higher age to be associated with these infections, independently of the presence of dementia. Our results suggest that different psychiatric diagnoses are associated with a heightened or lowered risk of bacterial infections and, furthermore, that clinical routine infection-screenings for elderly psychiatric patients seems to be reasonable