Preserved response of mitochondrial function to short-term endurance training in skeletal muscle of heart transplant recipients

OBJECTIVES: We sought to determine whether intrinsic mitochondrial function and regulation were altered in heart transplant recipients (HTRs) and to investigate the response of mitochondrial function to six-week endurance training in these patients. BACKGROUND: Despite the normalization of central oxygen transport during exercise, HTRs are still characterized by limited exercise capacity, which is thought to result from skeletal muscle metabolic abnormalities. METHODS: Twenty HTRS agreed to have vastus lateralis biopsies and exercise testing: before and after training for 12 of them and before and after the same control period for eight subjects unwilling to train. Mitochondrial respiration was evaluated on saponin-permeabilized muscle fibers in the absence or presence (maximum respiration rate [V(max)]) of saturating adenosine diphosphate. RESULTS: Mitochondrial function was preserved at the level of sedentary subjects in untrained HTRs, although they showed 28 +/- 5% functional aerobic impairment (FAI). After training, V(max), citrate synthase, cytochrome c oxidase, and mitochondrial creatine kinase (CK) activities were significantly increased by 48%, 40%, 67%, and 53%, respectively (p < 0.05), whereas FAI decreased to 12 +/- 5% (p < 0.01). The control of mitochondrial respiration by creatine and mitochondrial CK was also improved (p < 0.01), suggesting that phosphocreatine synthesis and transfer by the mitochondrial CK become coupled to oxidative phosphorylation, as shown in trained, healthy subjects. CONCLUSIONS: In HTRs, the mitochondrial properties of skeletal muscle were preserved and responded well to training, reaching values of physically active, healthy subjects. This suggests that, in HTRs, immunosuppressive drugs do not alter the intrinsic muscle oxidative capacities and that the patients' physical handicap results from nonmitochondrial mechanisms.     

Privately insured medical patients are more likely to have a head CT

Previous studies suggest overuse disparity of head computed tomography (CT) in white pediatric trauma patients with minor head injuries. Our study is meant to determine if race or insurance status impacts the probability of obtaining head CT in patients with a Glasgow Coma Scale (GCS)?=?15. Using the 2008–2010 National Hospital Ambulatory Medical Care Survey for Emergency Departments (NHAMCS) database, the following variables were analyzed: race, emergency medical services (EMS) arrival, triage category, admission status, gender, age, and insurance status. Patients with injuries were excluded. All patients included had GCS?=?15. In univariate analysis, head CT is more likely to be obtained for patients in the following categories: Medicare insured, private insurance, Medicaid insured, and self-pay, EMS arrival, triage category immediate, and age >75 years. In logistic regression, race (white vs. black) was no longer significant, but there was disparity based on insurance status with privately insured patients more likely to receive a head CT (OR?=?1.683, 95 % CI?=?1.255–2.259). After controlling for the above inclusion variables and focusing on patients less likely to need CT (non-traumatic with GCS?=?15), privately insured patients were more likely to receive a head CT compared with uninsured. Race alone was not associated with an increased probability of receiving a head CT.     

HIV Care After Jail: Low Rates of Engagement in a Vulnerable Population

The criminal justice system is a critical area of focus to improve HIV outcomes and reduce health disparities. We analyzed demographic, incarceration, socioeconomic, and clinical data for HIV-positive persons released to the community from the Dallas County Jail (1450 incarcerations, 1111 unique individuals) between January 2011 and November 2013. The study population was 68% black and 14% Hispanic; overall linkage to care within 90 days of release was 34%. In adjusted analyses, Hispanics were more likely to link than whites (aOR 2.33 [95% CI: 1.55–3.50]), and blacks were as likely to link as whites (aOR 1.14 [95% CI: 0.84–1.56]). The majority of HIV-positive jail releases did not re-engage in HIV care after release, though Hispanics were twice as likely as other groups to link to care. Further efforts are needed to improve the transition from jail to community HIV care with particular attention to issues of housing, mental illness, and substance use.     

Intramuscular ketorolac versus oral ibuprofen for pain relief in first-trimester surgical abortion: a randomized clinical trial

Objective

Oral nonsteroidal antiinflammatory medications (NSAIDs) have been shown to reduce pain with first-trimester surgical abortion compared to placebo, but it is unclear if one NSAID is better than another. Some providers administer intramuscular ketorolac, though data regarding its efficacy in abortion are limited. This study was designed to compare oral ibuprofen to intramuscular ketorolac for pain management during first-trimester surgical abortion.

Study Design

This was a randomized, double-blind, controlled trial. Women undergoing first-trimester surgical abortion with local anesthesia were randomized to preprocedural oral ibuprofen, 800 mg given 60–90 min preprocedure, or intramuscular ketorolac, 60 mg given 30–60 min preprocedure. The primary outcome was pain with uterine aspiration on a 21-point, 0–100, numerical rating scale. Secondary outcomes included pain with cervical dilation, postoperative pain and patient satisfaction.

Results

Ninety-four women were enrolled; 47 were randomized to ibuprofen and 47 to ketorolac. The groups did not differ with regards to demographics, reproductive history or Depression Anxiety Stress Scale scores. Mean pain scores for suction curettage did not differ between groups (52.3 vs. 56.2, p=.53). There was also no difference in pain with cervical dilation (41.6 vs. 45.4, p=0.48) or postoperative pain (22.3 vs. 15.0 p=.076), though patients in the ketorolac group experienced significantly greater arm pain than those who received a placebo injection (30.4 vs. 15.6, p<.001). Satisfaction with pain control did not differ significantly by group.

Conclusions

Intramuscular ketorolac does not offer superior pain control compared to oral ibuprofen for first-trimester surgical abortion.

Implications

Intramuscular ketorolac does not offer superior pain control over oral ibuprofen during first-trimester surgical abortion, is more expensive and causes patients significant arm discomfort. Its use should therefore be reserved for patients who cannot tolerate oral NSAIDs.     

A new der(1;7)(q10;p10) leading to a singular 1p loss in a case of glioblastoma with oligodendroglioma component

The combined 1p‐/19q‐ deletions in oligodendrogliomas originate from translocation between both chromosomes. In the few cases of oligoastrocytomas and glioblastomas with an oligodendroglioma component (GBMO) where only 1p deletion was described, the origin remains unknown. We report the first case of GBMO, in which a single 1p deletion was detected and was linked to a translocation between chromosomes 1 and 7. Fresh surgical specimens were collected during surgery and the samples were used for cell culture, touch preparation smear slides (TP slides) and DNA extraction. Peripheral venous blood was also collected from the patient. G‐banding using Trypsin and stained with Giemsa (GTG) banding and karyotyping were performed and 1p‐/19q‐, TP53, PTEN and c‐MYC were analyzed by fluorescent in situ hybridization (FISH). Multicolor FISH (mFISH) and microsatellites analyses were also performed to complete the investigation. Three‐dimensional quantitative FISH (3D‐QFISH) of telomeres was performed on nuclei from TP slides and analyzed using TeloView^TM to determine whether the 3D telomere profile as an assessment of telomere dysfunction and a characterization of genomic instability could predict the disease aggressiveness. An unbalanced chromosomal translocation was found in all metaphases and confirmed by mFISH. The karyotype of the case is: 50～99,XXX, +der(1;7)(q10;p10),inc[47] The derivative chromosome was found in all 47 analyzed cells, but the number of derivatives varied from one to four. There was neither imbalance in copy number for genes TP53 and PTEN, nor amplification of c‐MYC gene. We did not find loss of heterozygosity with analysis of microsatellite markers for chromosomes 1p and 19q in tumor cells. The 3D‐telomere profile predicted a very poor prognostic and short‐term survival of the patient and highlights the potential clinical power of telomere signatures as a solid biomarker of GBMO. Furthermore, this translocation between chromosomes 1 and 7 led to a singular 1p deletion in this GBMO and may generate the 1p and 7q deletions.     

A Sequence of events model of episodic memory shows parallels in rats and humans

A critical feature of episodic memory is the ability to remember the order of events as they occurred in time, a capacity shared across species including humans, nonhuman primates, and rodents. Accumulating evidence suggests that this capacity depends on a network of structures including the hippocampus and the prefrontal cortex, but their respective contributions remain poorly understood. As addressing this important issue will require converging evidence from complementary investigative techniques, we developed a cross‐species, nonspatial sequence memory task suitable for behavioral and neurophysiological studies in rodents and in humans. The task involves the repeated presentation of sequences of items (odors in rats and images in humans) and requires subjects to make a judgment as to whether each item is presented “in sequence” or “out of sequence.” To shed light on the cognitive processes and sequence representations supporting performance, different types of “out of sequence” probe trials were used including: (i) repeating an item from earlier in the sequence (Repeats; e.g., ABA D), (ii) skipping ahead in the sequence (Skips; e.g., ABD ), and (iii) inserting an item from a different sequence into the same ordinal position (Ordinal Transfers; e.g., A2 CD). We found a remarkable similarity in the performance of rats and humans, particularly in the pattern of results across probe trial types. Thus, the results suggest that rats and humans not only remember the sequences of events, but also use similar underlying cognitive processes and mnemonic representations. This strong cross‐species correspondence validates this task for use in future basic and clinical interdisciplinary studies aimed at examining the neural mechanisms underlying episodic memory. © 2014 Wiley Periodicals, Inc.