A skills-training group intervention model to assist persons in reducing risk behaviors for HIV infection

Fifteen gay men with a history of recent high-risk sexual activities attended seven group sessions that provided risk education, training in self-management skills pertinent to risk reduction, sexual assertiveness training, and problem solving with respect to health consciousness, social supports, and efficacy of risk-reduction change. Before and after intervention, subjects completed measures of AIDS risk knowledge, sexual practices occurring over 4-month retrospective periods, and self-monitored records of ongoing sexual activities and participated in role plays assessing behavioral assertiveness skill for resisting high-risk coercions. Eight-month follow-up data were also collected. Subjects exhibited substantial and well-maintained change following intervention in behaviors relevant to HIV infection risk, including frequency of unprotected anal intercourse (which decreased to near-zero levels), condom use (which increased to almost 90% of intercourse occasions), and in an index that reflects the multiplicative function of risk behaviors frequency by the number of partners with whom high-risk behaviors occurs. This demonstration provides further evidence that skills-training approaches can assist individuals in implementing behavior changes to reduce risk for AIDS and identifies a model relevant to counseling efforts in AIDS prevention programs, HIV counseling and testing programs, drug abuse and STD clinics, and other applied settings.     

Automated DNA diagnostics using an ELISA-based oligonucleotide ligation assay.

DNA diagnostics, the detection of specific DNA sequences, will play an increasingly important role in medicine as the molecular basis of human disease is defined. Here, we demonstrate an automated, nonisotopic strategy for DNA diagnostics using amplification of target DNA segments by the polymerase chain reaction (PCR) and the discrimination of allelic sequence variants by a colorimetric oligonucleotide ligation assay (OLA). We have applied the automated PCR/OLA procedure to diagnosis of common genetic diseases, such as sickle cell anemia and cystic fibrosis (delta F508 mutation), and to genetic linkage mapping of gene segments in the human T-cell receptor beta-chain locus. The automated PCR/OLA strategy provides a rapid system for diagnosis of genetic, malignant, and infectious diseases as well as a powerful approach to genetic linkage mapping of chromosomes and forensic DNA typing.     

The biomechanical functional demand placed on knee and hip muscles of older adults during stair ascent and descent

Age-related decline in physical capabilities may lead to older adults experiencing difficulty in performing everyday activities due to high demands placed on the muscles of their lower extremity. This study aimed to determine the biomechanical functional demand in terms of joint moments and maximal muscle capabilities at the knee and hip joints while older adults performed stair ascent (SA) and stair descent (SD). Eighty-four healthy older adults aged 60-88 years were tested. A torque dynamometer attached to a purpose-built plinth was utilized to measure muscle moments at the knee and hip joints. Participants also underwent full body 3-D biomechanical assessment of stair ascent and descent using an 8-camera VICON system (120 Hz) with 3 Kistler force plates. Stair negotiation required knee extensor moments in excess of the maximum isometric muscle strength available (SA 103%, SD 120%). For the hip, the levels of demand were high, but were slightly lower than those of the knee joint. Stair negotiation placed a high level of demand on the knee extensors with demand in SA reaching maximal isometric capacity and demand in SD exceeding maximal isometric capacity. The levels of demand leave little reserve capacity for the older adult to draw on in unexpected situations or circumstances.     

Precordial ST-segment mapping. 2. Effects of oxygen inhalation on ischemic injury in patients with acute myocardial infarction.

Precordial ST-segment mapping was serially applied in the Coronary Care Unit for the study of the effect of oxygen inhalation on the ischemic injury in 17 patients with acute anterior transmural myocardial infarction. A 49-lead ECG system was used. The sum of all ST elevations (sigmaST) recorded was taken as an index of magnitude of ischemic injury and the number of recording sites showing ST elevation (NST) was taken as an index of extent of ischemic damage. Stability of the precordial maps was observed over a period of one hour while the patients were on ambient air. Oxygen inhalation for a mean of 66 min resutled in a fourfold increase of PaO2 and a mean of 16% reduction of both sigmaST and NST. When the patients were returned to ambient air breathing, a mean of 13% increase of sigmaST and 19% of NST from the levels recorded during oxygen inhalation were observed. Levels of sigmaST and NST on ambient air following discontinuation of oxygen inhalation were not significantly different from the corresponding values from maps recorded before onset of oxygen breathing. Blood pressure and heart rate remained unchanged throughout the study. Clinical status of the patients was unchanged during the study period save for two patients who showed changes in intensity of their chest pain.     

Precordial ST-segment mapping 4. Experience with mapping of ST-segment depression in anterior transmural myocardial infarction

In order to assess the relative significance of precordial ST-segment elevations and depressions, 32 patients with anterior transmural myocardial infarction were studied utilizing serial 49-lead precordial maps. Theoretically, zones of ST-segment depression adjacent to major zones of ST-segment elevation might represent border areas of mild ischemia, and hence could be more readily amenable to intervention therapy. As expected, an extensive zone of ST-segment elevation was observed precordially in each of these patients. However, zones of ST-segment depression in adjacent areas were noted to occur inconsistently, were limited in distribution and magnitude, and bore no fixed relationship to zones of ST-segment elevation. Thus, mapping of precordial ST-segment depression in anterior transmural infarction probably has a limited role in assessing evolution of ischemic injury or therapy in these patients. This finding does not, however, vitiate the significance of ST-segment depressions in angina, intermediate coronary syndrome, or non-transmural infarction, conditions which may deserve further study using mapping techniques.     

Executive function deficits and glutamatergic protein alterations in a progressive 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine mouse model of Parkinson's disease

Changes in executive function are at the root of most cognitive problems associated with Parkinson's disease. Because dopaminergic treatment does not necessarily alleviate deficits in executive function, it has been hypothesized that dysfunction of neurotransmitters/systems other than dopamine (DA) may be associated with this decrease in cognitive function. We have reported decreases in motor function and dopaminergic/glutamatergic biomarkers in a progressive 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) Parkinson's mouse model. Assessment of executive function and dopaminergic/glutamatergic biomarkers within the limbic circuit has not previously been explored in our model. Our results show progressive behavioral decline in a cued response task (a rodent model for frontal cortex cognitive function) with increasing weekly doses of MPTP. Although within the dorsolateral (DL) striatum mice that had been given MPTP showed a 63% and 83% loss of tyrosine hydroxylase and dopamine transporter expression, respectively, there were no changes in the nucleus accumbens or medial prefrontal cortex (mPFC). Furthermore, dopamine‐1 receptor and vesicular glutamate transporter (VGLUT)?1 expression increased in the mPFC following DA loss. There were significant MPTP‐induced decreases and increases in VGLUT‐1 and VGLUT‐2 expression, respectively, within the DL striatum. We propose that the behavioral decline following MPTP treatment may be associated with a change not only in cortical–cortical (VGLUT‐1) glutamate function but also in striatal DA and glutamate (VGLUT‐1/VGLUT‐2) input. © 2015 Wiley Periodicals, Inc.     

Mefloquine induces oxidative stress and neurodegeneration in primary rat cortical neurons

Mefloquine is an effective antimalarial that can cause adverse neurological events including headache, nausea, fatigue, insomnia, anxiety and depression. In this study, we examined the oxidative stress response in primary rat cortical neurons treated with mefloquine by quantifying oxidative stress markers glutathione (GSH) and F₂-isoprostanes (F₂-isoPs). Furthermore, we examined whether mefloquine induces synaptodendritic degeneration of primary rat cortical neurons. GSH was quantified in cortical neurons after 24-h treatment with mefloquine (0, 1, 5, 10 μM) using monochlorobimane. F₂-isoPs were quantified in cortical neurons after 24-h treatment with mefloquine (0, 1, 5, 10 μM) using a stable isotope dilution method with detection by gas chromatography/mass spectrometry and selective ion monitoring. The concentration dependent decrease in GSH and the concomitant increase of F₂-isoPs indicates the presence of oxidative stress in primary rat cortical neurons treated with mefloquine. Following a 24-h treatment with mefloquine, primary rat cortical neurons (0, 5, 10 μM) were fixed with 4% paraformaldehyde. Images from eight optical sections covering a distance of 2.88 μm on the z-axis were acquired using a confocal laser scanning unit. Traced images were analyzed with NeuroExplorer, a neurophysiological data analysis package. Mefloquine induces a concentration dependent decrease in the number of spines per neuron and the spine density, suggesting that mefloquine induced oxidative stress may be associated with the synaptodendritic degeneration. Together with previous work, there is strong evidence that a relationship exists between calcium homeostasis disruption, ER stress response, the oxidative stress response, and neurodegeneration. Understanding how oxidative stress alters the morphology of cortical neurons treated with mefloquine will provide further insight into the mechanism(s) related to clinically observed adverse neurological events.     

Residency Training in Pediatric and Adolescent Gynecology Across Obstetrics and Gynecology Residency Programs: A Cross-Sectional Study

Study ObjectiveTo estimate the prevalence of Pediatric and Adolescent Gynecology formal training in the United States Obstetric and Gynecology residency programs.DesignProspective, anonymous, cross-sectional study.ParticipantsUnited States program directors of Obstetrics and Gynecology residency programs, N = 242; respondents 104 (43%).Results104 residency programs responded to our survey. Among the 104 residency programs, 63% (n = 65) have no formal, dedicated Pediatric and Adolescent Gynecology clinic, while 83% (n = 87) have no outpatient Pediatric and Adolescent Gynecology rotation. There is no significant difference in the amount of time spent on a Pediatric and Adolescent Gynecology rotation among residents from institutions with a Pediatric and Adolescent Gynecology fellowship (P = .359), however, the number of surgeries performed is significantly higher than those without a Pediatric and Adolescent Gynecology fellowship (P = .0020). When investigating resident competency in Pediatric and Adolescent Gynecology, program directors reported that residents who were taught in a program with a fellowship-trained Pediatric and Adolescent Gynecology faculty were significantly more likely to be able to interpret results of selected tests used to evaluate precocious puberty than those without (P = .03).ConclusionsResidency programs without fellowship trained Pediatric and Adolescent Gynecology faculty or an established Pediatric and Adolescent Gynecology fellowship program may lack formal training and clinical exposure to Pediatric and Adolescent Gynecology. This information enables residency directors to identify deficiencies in their own residency programs and to seek improvement in resident clinical experience in Pediatric and Adolescent training.     

More than motor impairment: A spatiotemporal analysis of cognitive impairment and associated neuropathological changes following cortical photothrombotic stroke

There is emerging evidence suggesting that a cortical stroke can cause delayed and remote hippocampal dysregulation, leading to cognitive impairment. In this study, we aimed to investigate motor and cognitive outcomes after experimental stroke, and their association with secondary neurodegenerative processes. Specifically, we used a photothrombotic stroke model targeting the motor and somatosensory cortices of mice. Motor function was assessed using the cylinder and grid walk tasks. Changes in cognition were assessed using a mouse touchscreen platform. Neuronal loss, gliosis and amyloid-β accumulation were investigated in the peri-infarct and ipsilateral hippocampal regions at 7, 28 and 84 days post-stroke. Our findings showed persistent impairment in cognitive function post-stroke, whilst there was a modest spontaneous motor recovery over the investigated period of 84 days. In the peri-infarct region, we detected a reduction in neuronal loss and decreased neuroinflammation over time post-stroke, which potentially explains the spontaneous motor recovery. Conversely, we observed persistent neuronal loss together with concomitant increased neuroinflammation and amyloid-β accumulation in the hippocampus, which likely accounts for the persistent cognitive dysfunction. Our findings indicate that cortical stroke induces secondary neurodegenerative processes in the hippocampus, a region remote from the primary infarct, potentially contributing to the progression of post-stroke cognitive impairment.     

Cephalad Movement of Morphine and Fentanyl in Humans after Intrathecal Injection

Background: Despite decades of use, controversy remains regarding the extent and time course of cephalad spread of opioids in cerebrospinal fluid (CSF) after intrathecal injection. The purpose of this study was to examine differences between two often used opioids, morphine and fentanyl, in distribution in the CSF after intrathecal injection.

Methods: Eight healthy volunteers received intrathecal injection of morphine (50 [mu]g) plus fentanyl (50 [mu]g) at a lower lumbar interspace. CSF was sampled through a needle in an upper lumbar interspace for 60-120 min. At the end of this time, a sample was taken from the lower lumbar needle, and both needles were withdrawn. CSF volume was determined by magnetic resonance imaging. Pharmacokinetic modeling was performed with NONMEM.

Results: Morphine and fentanyl peaked in CSF at the cephalad needle at similar times (41 +/- 13 min for fentanyl, 57 +/- 12 min for morphine). The ratio of morphine to fentanyl in CSF at the cephalad needle increased with time, surpassing 2:1 by 36 min and 4:1 by 103 min. CSF concentrations did not correlate with weight, height, or lumbosacral CSF volume. The concentrations of morphine and fentanyl at both sampling sites were well described by a simple pharmacokinetic model. The individual model parameters did not correlate with the distance between the needles, CSF volume, patient height, or patient weight.