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Cardiovascular diseases represent the largest worldwide cause of morbidity and mortality. Common signs and symptoms of cardiovascular disease are well characterized and taught in medical curricula, allowing clinicians to quickly recognize and diagnose the more acute and emergent cardiovascular diseases. Dermatological features associated with cardiovascular diseases are less understood but very valuable to appreciate in clinical practice. The present investigation evaluates heart conditions such as heart failure, atherosclerosis, infective endocarditis, and Takotsubo cardiomyopathy, highlighting dermatologic signs that indicate underlying cardiovascular pathology and serve as important diagnostic and prognostic markers., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kaye et al.)

Objective: Analyze joint effects of race and social determinants on survival outcomes for patients undergoing total laryngectomy for advanced or recurrent laryngeal cancer at a tertiary care institute., Methods: Retrospective chart review of adult patients undergoing total laryngectomy for laryngeal cancer at a tertiary care center from 2013 to 2020. Extracted data included demographics, pathological staging and features, treatment modalities, and outcomes such as recurrence, fistula formation, and 2- and 5-year disease-free survival (DFS) and overall survival (OS). Area Deprivation Index (ADI) was calculated for each patient., Results: Among 185 patients identified, 113 were Black (61.1%) and 69 were White (37.3%). No significant differences were observed between racial groups regarding age, gender, ADI, or cancer stage. There was no significant difference in 2-year DFS/OS between groups. ADI was comparable between racial groups, with the majority in the highest deprivation quintile (63.8% of Whites vs. 62.5% of Blacks). No significant differences were observed in gender, race, cancer stage, positive margins, extracapsular extension, or smoking status among ADI quintiles. We observed a significant difference in 2-year DFS stratified by ADI (p = 0.025). Stratifying by ADI and race revealed improved survival of White patients in lower quintiles but higher survival of Black patients in the highest disparity quintile (p = 0.013)., Conclusion: Overall, survival outcomes by race were comparable among laryngectomy patients, but there was a significant difference in 2-year DFS when stratified by ADI. Further research into survival outcomes related to social determinants is needed to better delineate their effects on head and neck cancer outcomes., Level of Evidence: 3 Laryngoscope, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Introduction: Mild therapeutic hypothermia (MTH) is an exciting nonpharmaceutical otoprotection strategy. In this study, we applied simple irrigation of the tympanic and mastoid cavities to understand the timing of both achieving MTH and recovery back to euthermic temperatures for application in the clinical setting., Methods: Three human temporal bones were used in this study in the temporal bone laboratory. A standard mastoidectomy was performed on each followed by the insertion of temperature probes into the basal turn of the cochlea via a middle cranial fossa approach. The temporal bones were warmed in heated bead baths to 37°C. The tympanic and mastoid cavities were then irrigated with room temperature water, and intracochlear temperature readings were recorded every minute. After 15 min, irrigation was stopped, and temperature readings were collected until temporal bones returned to euthermic levels., Results: Intracochlear MTH was achieved within the first minute of irrigating the tympanic and mastoid cavities. Intracochlear temperatures plateaued after 5 min around 30°C. Discontinuation of irrigation resulted in the temperature rising logarithmically above the MTH levels after 9-10 min., Conclusion: Intracochlear MTH can be achieved via irrigation of the tympanic and mastoid cavities with room temperature irrigation within 60 s. After irrigation for 5 min, hypothermic temperatures will remain therapeutic for 10 min following cessation of irrigation., (© 2024 S. Karger AG, Basel.)

Purpose: Our primary aim was to understand and describe the impact of COVID-19 on the incidence and etiology of facial trauma in the state of Mississippi., Methods: Retrospective review of facial trauma-related Emergency Department encounters in Mississippi from March 11, 2019 to March 10, 2021, divided into three time periods using the state of Mississippi's Governor's Office Executive Orders. Chi-square tests and segmented linear regressions were used for analysis., Results: Patients presenting with facial trauma were typically male, 18-44 years old, and lived in urban zip codes. Insurance payors significantly differed across time periods. There were no significant differences in self-inflicted assault or accidental injury between the 3 time periods, with pre- and pandemic patients more likely to be self-pay while patients during recovery being more likely to have private insurance. During the pandemic, facial trauma from a family member, partner or spouse, or other person in the household significantly increased., Conclusion: Similar accidental facial trauma trends may reflect lower adherence to social distancing guidelines. The increase in facial trauma perpetrated by family members is consistent with reported increases in domestic violence during the pandemic. While overall facial trauma demographic patterns did not change significantly during the COVID-19 pandemic, there were notable changes in the etiology and insurance payor of facial trauma cases., Lay Summary: The COVID-19 pandemic impacted healthcare systems worldwide, and our study seeks to understand how the pandemic affected incidence of facial trauma., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To determine if hearing aid use in school aged children is impacted when upgraded to direct Bluetooth® enabled technology. We hypothesized that because children are better able to connect to their devices and headphones, they would be more inclined to use their hearing aids throughout the day, resulting in an increase in hearing aid compliance., Methods: This retrospective analysis examined changes in datalogging of hours of usage per day in 51 school aged children who underwent an upgrade from non-direct Bluetooth® hearing technology to direct Bluetooth®-enabled hearing technology., Results: Hours per day of hearing aid use in all hearing aid users significantly increased after upgrading to DBT enabled technology (6.82 vs 9.82, <0.001). There were no significant differences noted in hours before and after upgrade depending on race (p = 0.147), gender (p = 0.887), developmental delay (p = 0.749), type of hearing loss (p = 0.218), and degree of hearing loss (p = 0.551). However, when comparing private versus Medicaid insurance, there was noted to be a significant difference with the odds of an increase in hours of usage after upgrade being higher for those patients privately insured (OR = 1.247, p < 0.001, 95 % CI 1.093-1.422)., Conclusion: Direct Bluetooth® enabled hearing technology positively impacts children's hearing aid compliance, which has the potential improve speech and language outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Melanoma is currently the fifth most common cancer in the United States (US) and most often develop on areas that have increased sun exposure, such as the arms, legs, back or face. The incidence of primary cutaneous melanoma increases each year and curative treatment improves with earlier detection of disease. Primary cutaneous umbilical melanoma is extremely rare with as few as 46 cases reported worldwide. As a result, limited literature is available regarding the management of tumors originating in the umbilicus. By evaluating uncommon areas such as the umbilicus, earlier detection and possible intervention can be provided. We present a rare case of a 33-year-old female with a primary cutaneous melanoma of the umbilicus successfully treated with wide local excision (WLE) and sentinel lymph node biopsy (SLNB).

In the current Anthropocene Era, with numerous escalating challenges for biodiversity conservation, the inclusion of the social dimension into management decisions regarding wildlife and protected areas is critical to their success. By conducting 354 questionnaires in a Mediterranean protected area (the Biosphere Reserve of Bardenas Reales, Northern Spain), we aim to determine sociodemographic factors influencing knowledge levels and perceptions of species and functional groups as, emblematic and threatened. We found that hunters and animal husbandry workers knew more species than other social actors. Additionally, the perception of functional groups as threatened or emblematic differed between social actor groups, with statistically significant associations between perceptions and the characteristics of respondents. Interestingly, we found that although elusive steppe species are globally considered as endangered, these species were the least known by all social actor groups and rarely perceived as emblematic. This research is a novel approach and provides a better understanding of how perceptions can facilitate conservation decisions, particularly regarding endangered species., (© 2021. The Author(s).)

The specific questions addressed from this research include: (1) Does high-intensity acute exercise improve memory?, (2) If so, do the mechanisms occur via encoding, consolidation, or retrieval? and (3) If acute exercise occurs in multiple phases of memory (e.g., before encoding and during consolidation), does this have an additive effect on memory? Three experimental, within-subject, counterbalanced studies were conducted among young adults. High-intensity exercise involved a 20-minutes bout of exercise at 75% of heart rate reserve. Memory was evaluated from a word-list task, including multiple evaluations out to 24-hours post-encoding. The timing of the exercise and memory assessments were carefully positioned to evaluate whether any improvements in memory were driven by mechanisms related to encoding, consolidation, and/or retrieval. We demonstrated that high-intensity acute exercise enhanced memory. This effect was robust (repeatable) and occurred through encoding, consolidation and retrieval-based mechanisms. Further, incorporating acute exercise into multiple phases of memory additively enhanced memory function., Competing Interests: The authors have declared that no competing interests exist.

Cellular transdifferentiation changes mature cells from one phenotype into another by altering their gene expression patterns. Manipulating expression of transcription factors, proteins that bind to DNA promoter regions, regulates the levels of key developmental genes. Viral delivery of transcription factors can efficiently reprogram somatic cells, but this method possesses undesirable side effects, including mutations leading to oncogenesis. Using protein transduction domains (PTDs) fused to transcription factors to deliver exogenous transcription factors serves as an alternative strategy that avoids the issues associated with DNA integration into the host genome. However, lysosomal degradation and inefficient nuclear localization pose significant barriers when performing PTD-mediated reprogramming. Here, we investigate a novel PTD by placing a secretion signal sequence next to a cleavage inhibition sequence at the end of the target transcription factor-achaete scute homolog 1 (ASCL1), a powerful regulator of neurogenesis, resulting in superior stability and nuclear localization. A fusion protein consisting of the amino acid sequence of ASCL1 transcription factor with this novel PTD added can transdifferentiate cerebral cortex astrocytes into neurons. Additionally, we show that the synergistic action of certain small molecules improves the efficiency of the transdifferentiation process. This study serves as the first step toward developing a clinically relevant in vivo transdifferentiation strategy for converting astrocytes into neurons.

Deuterium gas puff Z pinches have been used for generation of strong neutron fluxes on the MA class pulse power machines. Due to the low electron density of deuterium Z-pinch plasma, regular laser diagnostics in the visible range cannot be used for observation and study of the pinch. Laser probing at the wavelength of 1064 nm was used for visualization of deuterium plasma. Infrared schlieren and interferometry diagnostics showed the deuterium gas puff plasma dynamics, instabilities, and allowed for the reconstruction of the profile of the plasma density.

Background: Exhaled aerosol patterns, also called aerosol fingerprints, provide clues to the health of the lung and can be used to detect disease-modified airway structures. The key is how to decode the exhaled aerosol fingerprints and retrieve the lung structural information for a non-invasive identification of respiratory diseases., Objective and Methods: In this study, a CFD-fractal analysis method was developed to quantify exhaled aerosol fingerprints and applied it to one benign and three malign conditions: a tracheal carina tumor, a bronchial tumor, and asthma. Respirations of tracer aerosols of 1 µm at a flow rate of 30 L/min were simulated, with exhaled distributions recorded at the mouth. Large eddy simulations and a Lagrangian tracking approach were used to simulate respiratory airflows and aerosol dynamics. Aerosol morphometric measures such as concentration disparity, spatial distributions, and fractal analysis were applied to distinguish various exhaled aerosol patterns., Findings: Utilizing physiology-based modeling, we demonstrated substantial differences in exhaled aerosol distributions among normal and pathological airways, which were suggestive of the disease location and extent. With fractal analysis, we also demonstrated that exhaled aerosol patterns exhibited fractal behavior in both the entire image and selected regions of interest. Each exhaled aerosol fingerprint exhibited distinct pattern parameters such as spatial probability, fractal dimension, lacunarity, and multifractal spectrum. Furthermore, a correlation of the diseased location and exhaled aerosol spatial distribution was established for asthma., Conclusion: Aerosol-fingerprint-based breath tests disclose clues about the site and severity of lung diseases and appear to be sensitive enough to be a practical tool for diagnosis and prognosis of respiratory diseases with structural abnormalities.

We demonstrate and characterize a highly linearly polarized (18.8 dB) narrow spectral emission (<80 pm) from an all-fiber Tm laser utilizing femtosecond-laser-written fiber Bragg gratings. Thermally-dependent anisotropic birefringence is observed in the FBG transmission, the effects of which enable both the generation and elimination of highly linearly polarized output. To our knowledge, this is the first detailed study of such thermal anisotropic birefringence in femtosecond-written FBGs.

B lymphocyte memory generates antibody-secreting cells (ASCs) that represent a source of protective antibodies that may be exploited for therapeutics. Here we vaccinated four donors with Pneumovax®23 and produced human monoclonal antibodies (hmAbs) from ASCs. We have cloned 137 hmAbs and the specificities of these antibodies encompass 19 of the 23 serotypes in the vaccine, as well as cell wall polysaccharide (CWPS). Although the majority of the antibodies are serotype specific, 12% cross-react with two serotypes. The Pneumovax®23 ASC antibody sequences are highly mutated and clonal, indicating an anamnestic response, even though this was a primary vaccination. Hmabs from 64% of the clonal families facilitate opsonophagocytosis. Although 9% of the total antibodies bind to CWPS impurity in the vaccine, none of these clonal families showed opsonophagocytic activity. Overall, these studies have allowed us to address unanswered questions in the field of human immune responses to polysaccharide vaccines, including the cross-reactivity of individual antibodies between serotypes and the percentage of antibodies that are protective after vaccination with Pneumovax®23., (Copyright © 2012 Elsevier GmbH. All rights reserved.)

In order to identify the combination of antibody-mediated mechanisms of neutralization that result from vaccination with anthrax vaccine adsorbed (AVA), we isolated antibody secreting cells from a single donor seven days after booster vaccination with AVA and generated nine fully human monoclonal antibodies (hmAb) with high specificity for protective antigen (PA). Two of the antibodies were able to neutralize lethal toxin in vitro at low concentrations (IC(50): p6C01, 0.12 μg/ml and p6F01, 0.45 μg/ml). Passive transfer of either of these hmAbs to A/J mice prior to challenge with lethal toxin conferred 80-90% protection. We demonstrate that hmAb p6C01 is neutralizing by preventing furin cleavage of PA in a dose-dependent manner, but the mechanism of p6F01 is unclear. Three additional antibodies were found to bind to domain 3 of PA and prevent oligomerization, although they did not confer significant protection in vivo and showed a significant prozone-like effect in vitro. These fully human antibodies provide insight into the neutralizing response to AVA for future subunit vaccine and passive immunotherapeutic cocktail design., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Labour force participation has been identified as a critical social and health issue facing people living with HIV/AIDS (PHAs). We conducted a scoping study (a form of literature synthesis that summarizes research findings, research activity, and identifies literature strengths and gaps) on labour force participation for PHAs, guided by a community advisory committee. We summarized information from 243 peer-reviewed articles and 42 reports from the grey literature, and synthesized the evidence into a preliminary conceptual framework with five components: (1) the meaning of work, (2) key factors (barriers and facilitators) influencing labour force participation, (3) factors affecting vulnerable populations, (4) strategies and supports for returning to or sustaining work, and (5) outcomes (benefits and risks) of labour force participation for individuals and employers. The framework supports the development of labour force initiatives requiring collaborative efforts in multiple domains (health, employment, community) by PHAs, rehabilitation professionals, employers, insurers, and policy makers.

The antiretroviral efficacy of 3'-azido-3'-deoxythymidine (AZT) is dependent upon intracellular mono-, di-, and triphosphorylation and incorporation into DNA in place of thymidine. Thymidine kinase 1 (TK-1) catalyzes the first step of this pathway. MOLT-3, human lymphoblastoid cells, were exposed to AZT continuously for 14 passages (P(1)-P(14)) and cultured for an additional 14 passages (P(15)-P(28)) without AZT. Progressive and irreversible depletion of the enzymatically active form of the TK-1 24-kDa monomer with loss of active protein was demonstrated during P(1)-P(5) of AZT exposure. From P(15) to P(28), both the 24- and the 48-kDa forms of TK-1 were undetectable and a tetrameric 96-kDa form was present. AZT-DNA incorporation was observed with values of 150, 133, and 108 molecules of AZT/10(6) nucleotides at the 10 microM plasma-equivalent AZT dose at P(1), P(5), and P(14), respectively. An exposure-related increase in the frequency of micronuclei (MN) was observed in cells exposed to either 10 or 800 microM AZT during P(1)-P(14). Analysis of the cell cycle profile revealed an accumulation of S-phase cells and a decrease in G(1)-phase cells during exposure to 800 microM AZT for 14 passages. When MOLT-3 cells were grown in AZT-free media (P(15)-P(29)), there was a reduction in AZT-DNA incorporation and MN formation; however, TK-1 depletion and the persistence of S-phase delay were unchanged. These data suggest that in addition to known mutagenic mechanisms, cells may become resistant to AZT partially through inactivation of TK-1 and through modulation of cell cycle components.

Iejimalides are novel macrolides that are cytostatic or cytotoxic against a wide range of cancer cells at low nanomolar concentrations. A recent study by our laboratory characterized the expression of genes and proteins that determine the downstream effects of iejimalide B. However, little is known about the cellular target(s) of iejimalide or downstream signaling that lead to cell-cycle arrest and/or apoptosis. Iejimalides have been shown to inhibit the activity of vacuolar H(+)-ATPase (V-ATPase) in osteoclasts, but how this inhibition may lead to cell-cycle arrest and/or apoptosis in epithelial cells is not known. In this study, MCF-7 breast cancer cells were treated with iejimalide A or B and analyzed for changes in cell-cycle dynamics, apoptosis, lysosomal pH, cytoplasmic pH, mitochondrial membrane potential, and generation of reactive oxygen species. Both iejimalides A and B sequentially neutralize the pH of lysosomes, induce S-phase cell-cycle arrest, and trigger apoptosis in MCF-7 cells. Apoptosis occurs through a mechanism that involves oxidative stress and mitochondrial depolarization but not cytoplasmic acidification. These data confirm that iejimalides inhibit V-ATPase activity in the context of epithelial tumor cells, and that this inhibition may lead to a lysosome-initiated cell death process., ((c) 2009 Wiley-Liss, Inc.)

Significant time and effort are often required to solve and complete a macromolecular crystal structure. The development of automated computational methods for the analysis, solution, and completion of crystallographic structures has the potential to produce minimally biased models in a short time without the need for manual intervention. The PHENIX software suite is a highly automated system for macromolecular structure determination that can rapidly arrive at an initial partial model of a structure without significant human intervention, given moderate resolution, and good quality data. This achievement has been made possible by the development of new algorithms for structure determination, maximum-likelihood molecular replacement (PHASER), heavy-atom search (HySS), template- and pattern-based automated model-building (RESOLVE, TEXTAL), automated macromolecular refinement (phenix. refine), and iterative model-building, density modification and refinement that can operate at moderate resolution (RESOLVE, AutoBuild). These algorithms are based on a highly integrated and comprehensive set of crystallographic libraries that have been built and made available to the community. The algorithms are tightly linked and made easily accessible to users through the PHENIX Wizards and the PHENIX GUI.

Wernicke's encephalopathy may result in severe morbidity and possible mortality when unrecognized. We report a distinctive acid-base pattern that has not been associated with this syndrome. This is a case series of patients with Wernicke's encephalopathy who had an arterial blood gas measurement performed on initial presentation. Exclusion criteria were patients with an unclear diagnosis of Wernicke's encephalopathy and those for whom no arterial blood gas measurement was performed. Four patients with Wernicke's encephalopathy were included in the analysis. All 4 patients exhibited an anion-gap (primary) metabolic acidosis, accompanied by a primary respiratory alkalosis. Three of 4 patients exhibited a significant lactic acidosis. None of the patients had any competing diagnoses or dysfunction to account for this acid-base pattern. Patients with Wernicke's encephalopathy may exhibit a distinctive acid-base pattern consisting of a primary metabolic acidosis in conjunction with a primary respiratory alkalosis. Observation of this acid-base disturbance should prompt clinicians to consider thiamine deficiency disorders as a possible cause.

The question whether the nucleobases can be synthesized in interstellar space is of fundamental significance in considerations of the origin of life. Adenine is formally the HCN pentamer, and experiments have demonstrated that adenine is formed under certain conditions by HCN pentamerization in gas, liquid, and condensed phases. Most mechanistic proposals invoke the intermediacy of the HCN tetramer AICN (4), and it is thought that adenine synthesis is completed by addition of the 5(th) HCN to 4 to form amidine 5 and subsequent pyrimidine cyclization. In this context, we have been studying the mechanism for prebiotic pyrimidine-ring formation of monocyclic HCN-pentamers with ab initio electronic structure theory. The calculations model gas phase chemistry, and the results primarily inform discussions of adenine synthesis in interstellar space. Purine formation requires tautomerization of 5 to the conjugated amidine 6 (via hydrogen-tunneling, thermally with H(+) -catalysis, or by photolysis) or to keteneimine 7 (by photolysis). It was found that 5-(N'-formamidinyl)-1H-imidazole-4-carbonitrile (6) can serve as a substrate for proton-catalyzed purine formation under photolytic conditions and N-(4-(iminomethylene)-1H-imidazol-5(4H)-ylidene)formamidine (7) can serve as a substrate for uncatalyzed purine formation under photolytic conditions. The absence of any sizeable activation barrier for the cyclization of 7 to the (Z)-imino form of 9H-adenine (Z)-2 is quite remarkable, and it is this feature that allows for the formation of the purine skeleton from 7 without any further activation.

Unlabelled: X-ray crystallography is the most widely used method to determine the 3D structure of protein molecules. One of the most difficult steps in protein crystallography is model-building, which consists of constructing a backbone and then amino acid side chains into an electron density map. Interpretation of electron density maps represents a major bottleneck in protein structure determination pipelines, and thus, automated techniques to interpret maps can greatly improve the throughput. We have developed WebTex, a simple and yet powerful web interface to TEXTAL, a program that automates this process of fitting atoms into electron density maps. TEXTAL can also be downloaded for local installation., Availability: Web interface, downloadable binaries and documentation at http://textal.tamu.edu

The effects of a variety of oxazolidinones, with different antibacterial potencies, including linezolid, on mitochondrial protein synthesis were determined in intact mitochondria isolated from rat heart and liver and rabbit heart and bone marrow. The results demonstrate that a general feature of the oxazolidinone class of antibiotics is the inhibition of mammalian mitochondrial protein synthesis. Inhibition was similar in mitochondria from all tissues studied. Further, oxazolidinones that were very potent as antibiotics were uniformly potent in inhibiting mitochondrial protein synthesis. These results were compared to the inhibitory profiles of other antibiotics that function by inhibiting bacterial protein synthesis. Of these, chloramphenicol and tetracycline were significant inhibitors of mammalian mitochondrial protein synthesis while the macrolides, lincosamides, and aminoglycosides were not. Development of future antibiotics from the oxazolidinone class will have to evaluate potential mitochondrial toxicity.

Automating the determination of novel macromolecular structures via X-ray crystallographic methods involves building a model into an electron-density map. Unfortunately, the conventional crystallographic asymmetric unit volumes are usually not well matched to the biological molecular units. In most cases, the facets of the asymmetric unit cut the molecules into a number of disconnected fragments, rendering interpretation by the crystallographer significantly more difficult. The FINDMOL algorithm is designed to quickly parse the arrangement of trace points (pseudo-atoms) derived from a skeletonized electron-density map without requiring higher level prior information such as sequence information or number of molecules in the asymmetric unit. The algorithm was tested with a variety of density-modified maps computed with medium- to low-resolution data. Typically, the resulting volume resembles the biological unit. In the remaining cases the number of disconnected fragments is very small. In all examples, secondary-structural elements such as alpha-helices or beta-sheets are easily identifiable in the defragmented arrangement. FINDMOL can greatly assist a crystallographer during manual model building or in cases where automatic model building can only build partial models owing to limitations of the data such as low resolution and/or poor phases.

In previous work (McKee EE, Bentley AT, Smith RM Jr, and Ciaccio CE, Biochem Biophys Res Commun 257: 466-472, 1999), the transport of guanine nucleotides into the matrix of intact isolated heart mitochondria was demonstrated. In this study, the time course and mechanisms of guanine nucleotide transport are characterized. Two distinct mechanisms of transport were found to be capable of moving guanine nucleotides across the inner membrane. The first carrier was saturable, displayed temperature dependence, preferred GDP to GTP, and did not transport GMP or IMP. When incubated in the absence of exogenous ATP, this carrier had a V(max) of 946 +/- 53 pmol. mg(-1). min(-1) with a K(m) of 2.9 +/- 0.3 mM for GDP. However, transport of GTP and GDP on this carrier was completely inhibited by physiological concentrations of ATP, suggesting that this carrier was not involved with guanine nucleotide transport in vivo. Because transport on this carrier was also inhibited by atractyloside, this carrier was consistent with the well-characterized ATP/ADP translocase. The second mechanism of guanine nucleotide uptake was insensitive to atractyloside, displayed temperature dependence, and was capable of transporting GMP, GDP, and GTP at approximately equal rates but did not transport IMP, guanine, or guanosine. GTP transport via this mechanism was slow, with a V(max) of 48.7 +/- 1.4 pmol. mg(-1). min(-1) and a K(m) = 4.4 +/- 0.4 mM. However, because the requirement for guanine nucleotide transport is low in nondividing tissues such as the heart, this transport process is nevertheless sufficient to account for the matrix uptake of guanine nucleotides and may represent the physiological mechanism of transport.

This case report examined whether a 26-year-old man with a 5-year history of nonsevere aplastic anemia could perform aerobic training and whether exercise was beneficial. Testing was performed at baseline and at 8 and 16 weeks and included complete blood tests, graded exercise tests with breath-by-breath gas analyses, and health status assessment with the Medical Outcomes Survey SF-12 health survey. Training consisted of treadmill walking for 25 minutes, 3 days a week for 16 weeks, at 75% of maximal heart rate. The patient successfully completed 16 weeks of training and had no adverse effects from testing or training. Training did not produce changes in disease-related measures (hematologic values) or impairment measures (cardiopulmonary measures of fitness). The mental component of the SF-12 improved from below 2 standard deviations from the population mean to within 1 standard deviation of the population mean. The benefits of aerobic training for this person with aplastic anemia were that he showed that he could participate in aerobic-type activities and that training appeared to improve his mental health.

Presence of guanine nucleotide within the matrix of mitochondria is uncontested; the mechanism by which GTP takes up residence in the matrix is unknown. In this report, we demonstrate for the first time that direct transport of guanine nucleotide across the inner membrane of heart mitochondria is possible. Transport of guanine nucleotides from the medium to the matrix was suggested by inhibition of translation in isolated rat heart mitochondria when GTP-gamma-S was added to the medium. This result suggested that GTP was one source of matrix GTP. Other sources were investigated by measuring matrix uptake and conversion to GTP of several purines, purine nucleosides, and purine nucleotides. Results demonstrated that [14C]-guanine and [3H]-guanosine were not taken up by isolated mitochondria and were not converted to any other compound. While [14C]-ATP and [3H]-AMP were taken up readily into the matrix, radioactivity was never associated with a guanine compound. [3H]-IMP was not taken up into the matrix and was never converted to another compound. Our data showed that label added as [3H]-GTP, [3H]-GDP, or [3H]-GMP was readily taken up and concentrated in the matrix of isolated mitochondria., (Copyright 1999 Academic Press.)

Healthy aspects of psychological functioning are often overlooked in traditional psychological assessment. When this happens, the client may become discouraged with his or her testing results, or perhaps worse, may feel that the assessor was not interested in obtaining a complete picture of who he or she is. Assessing healthy aspects of psychological functioning can be problematic, however; adding new instruments that only speak to one aspect of psychological functioning is not practical. A system is proposed in which one aspect of healthy psychological functioning--optimism--can be assessed using a standard projective test. Use of this scale can aid the assessor in conceptualizing the client's functioning and can also be a helpful tool to draw on in the course of treatment.

To reduce space requirements for implant electronics in in vivo telemetry applications, the purpose of this project was to develop and test a new data transmission method that utilizes the ionic properties of bodily fluids as the transmission medium. Motivated by an interest in using the new method to transmit information from a sensor which measures tension in anterior cruciate ligament (ACL) grafts, a sine wave was injected into a cadaver leg using platinum electrodes implanted into the lateral femoral epicondyle. The signal was detected by electromyogram (EMG) surface electrodes. The effect of transmission frequency, the current injected, interelectrode separation, distance of the electrodes from the joint line, and the surface of electrode placement on the signal attenuation was studied. The logarithmic relation between attenuation and frequency was constant from 2 kHz until 10 kHz. For frequencies above 10 kHz, the attenuation increased linearly at the rate of 1 dB/octave. Attenuation was inversely sensitive to both current and interelectrode separation with larger separations and currents giving less attenuation. Attenuation was significantly less for the lateral thigh surface than for the anterior surface and increased with increasing distance from the joint line for both surfaces. For the application of interest here, suitable values of transmission variables to avoid the possible negative consequences of injecting current into living tissue are a current of 3 mA injected at a frequency of 37 kHz. The values of reception variables for minimum attenuation are wide interelectrode separation (5 cm) with the electrodes placed 5 cm proximal of the joint line on the lateral surface of the thigh. With the exception of the surface which is application dependent, these values of the reception variables should also be appropriate for other applications.

Quantifying changes in the tension of an anterior cruciate ligament (ACL) graft in vivo during rehabilitative exercises is useful for developing the optimum rehabilitation for patients who have had reconstructive surgery. The purpose of the work reported is to design, build and test a telemetry system that can measure the in vivo ACL graft tension post-operatively. A commercially available fixation device is modified to sense the graft tension, house electronic components, transmit an output signal and pass the power generating signal. A transcutaneous inductive link is used to power the implanted telemetry electronics. The current difference technique is used to measure changes in two resistance strain gauges that monitor shear strain developed on the femoral fixation device by the ACL graft. This current regulates a frequency-modulated output signal that is transmitted using a new technique. Harnessing the ionic and volume conduction properties of the body fluids, the new technique involves injecting current subcutaneously into the tissue and then sensing the potential developed on the skin by surface electrodes. The waveform shape, amount of charge injected, charge density and current density are regulated to avoid tissue damage, pain and unwanted muscular stimulation. A signal conditioning board detects and converts the output to an analogue voltage for collection by a computer data-acquisition system. A performance evaluation demonstrates that the telemetry system either meets or exceeds all of the criteria necessary for the application.

The purpose of this study was to determine the cardiovascular health needs of university students living in residence. A survey was administered to students living in residence at a university in Nova Scotia, Canada to identify eating patterns, physical activity, smoking behaviours and perceived stress. Data were analyzed using descriptive statistics and chi-square tests of association. Qualitative data were collected using focus group interviews. Results showed that fewer than half of the students participated in exercise three or more times per week, and 82% are less than the recommended amount of fruits and vegetables. As perceived knowledge of CVD increased so did level of physical activity and consumption of fruits and vegetables. Fifty-six percent of students rated their stress as high or very high; exams and course assignments are a major cause of this stress. Fifteen percent of the university students surveyed were daily smokers. Barriers to a healthy lifestyle include time constraints and limited food choices in the residence cafeteria.

A polypoid malignant rhabdoid tumor of the duodenum is presented. The pattern of metastatic spread in this 58-year-old man included multiple duodenal and small intestinal transmural tumor implants and a large peribronchial lymph node causing superior vena cava syndrome. Microscopically, the tumor was composed of a diffuse population of rhabdoid cells characterized by homogeneous globular cytoplasmic inclusions that tended to indent or displace eccentric, vesicular nuclei with nucleoli. No glandular features were noted. Immunohistochemical and ultrastructural evaluation revealed that these inclusions contained vimentin, an intermediate filament of the mesenchymal cytoskeleton. Phenotypic features of a rhabdoid tumor have been reported in 10 poorly differentiated malignancies of the gastrointestinal tract. This is the first case report of a malignant rhabdoid tumor of the small intestine. Regardless of the site of the lesion, tumors showing these features are generally associated with a poor prognosis.

The authors' purpose in this study was to (1) compare the effects of three teaching methods on registered nurses' and licensed practical nurses' knowledge of medication error risk reduction strategies, and (2) to compare registered nurses' and licensed practical nurses' knowledge of medication error risk reduction strategies using a pretest/posttest design. Registered nurses (n = 129) and licensed practical nurses (n = 21) employed by two hospitals constituted the study sample. Subjects were assigned alternately to three intervention groups: videotape (n = 50); instructional booklet (n = 50); and lecture (n = 50). A 38-item test, including true-false, multiple choice, matching items and dosage calculation problems, was administered to subjects in each group before and after the teaching intervention. On the basis of the results, there was no statistically significant difference in total knowledge scores for the three intervention groups (F = 2.07, P = 0.130). Staff development instructors should consider the advantages of a videotape and instructional booklet over the time-intensive lecture strategy.

This article reports on a descriptive study of staff support in 116 hospices in the UK. The study took the form of a postal questionnaire survey. Before the survey an extensive review of the literature was carried out which highlighted the causes and effects of stress, both generally and in palliative care, along with coping strategies. The literature emphasised the intense nature of palliative care and the importance of having effective support mechanisms in place for staff (McKee, 1995). The results of this survey showed that, in general, hospices are attempting to deal with staff stress by offering group and/or individual support.

An extensive review of the literature was carried out which highlighted the causes and effects of stress, both generally and in palliative care, along with the coping strategies for stress. The literature emphasised the intense nature of palliative care and the importance of having effective support mechanisms in place for staff.

It has been known for some time that the addition of a crude yeast cytosolic fraction to isolated mitochondria stimulates the rate of amino acid incorporation into protein in the isolated organelles. However, the mechanism and importance of this phenomenon relative to mitochondrial function has not been established. While it has been assumed that this effect is at the level of translation, the recognition that newly synthesized mitochondrial translation products are rapidly degraded in isolated yeast mitochondria raises the possibility that cytosol affects amino acid incorporation by inhibiting proteolysis. Using pulse-chase experiments we demonstrate that the rate constants of degradation of the nascent products are not affected by yeast cytosol. Further, not only is proteolysis not inhibited by cytosol, but the loss of label caused by proteolysis is actually increased. This increase is directly related to an increase in the size of the nascent product pool which increases simply as a consequence of increasing the rate of translation. By utilizing an approach in which the loss of label due to proteolysis is minimized, the true stimulatory activity of the cytosolic fraction on synthesis was determined (2.1-fold vs. 1.3-fold by the previous method). Pulse-chase experiments in the presence of pactamycin, an initiation inhibitor, demonstrate that yeast cytosol causes an initial increase in the rate of translational initiation without increasing the rate of elongation. However, at later intervals the yeast cytosol acts primarily to maintain the rate of elongation which falls steadily in the controls. Finally, the presence of yeast cytosol dramatically increases the length of incubation time in which the mitochondrial preparation consumes oxygen and maintains coupled respiration, parameters that fall rapidly in the controls. Thus, a yeast cytosolic fraction may function to promote the stability of the mitochondrial preparation, which in turn may account for the increase in rates of translation, particularly with regard to maintaining rates of elongation.

Premature infants with birth weights from 1121 to 2000 gm were assigned randomly to two groups. Experimental group infants were placed on a microprocessor-controlled cradle that provided levels of motion and sound analogous to those of the third-trimester intrauterine environment. Periods of motion totaling 50% of the time were randomized on and off; motion speed was reduced 35% during a 12-hour night period. A uterine souffle sound was generated continuously but varied in pulse rate and volume with the motion and speed of the bed. Experimental group infants (n = 20) were placed on the cradle under a radiant warmer as soon as their condition was stable clinically. Control group infants (n = 18) were usually placed initially under a radiant warmer and transferred to an incubator when their condition was stable. Otherwise, both groups received standard newborn intensive care unit care. The mean length of hospital stay was significantly shorter for experimental group infants than for control group infants after controlling for gestational age and weight on entry to the study. Experimental group infants began nippling earlier and stopped requiring gavage feedings sooner. Experimental group infants had a decreased incidence of apnea. Blinded Brazelton Neonatal Behavioral Assessment Scale scores for the Orientation and Range of State cluster scales were significantly better for experimental group infants. A retrospective contrast group of preterm infants who met study criteria had an average length of stay similar to that of the control group infants. These data support the hypothesis that appropriate levels and kinds of stimulation may facilitate the maturation of preterm infants.

The sudden death on May 2 of RCN member Joy Reilly after a short illness has left her family, friends and colleagues devastated. Joy's death at the early age of 57 will leave a void in the RCN in Northern Ireland and in particular the South and East Belfast Branch. She played a key role in developing the RCN's effectiveness, especially as a Northern Ireland Board member and previously through the Psychiatric Society. She retired from her post as ward sister in 'Shimna' Knockbraken Healthcare Park (formerly Purdysburn Hospital) only last autumn. She will be sadly missed by her patients, colleagues and friends in the health service and by the many friends she made on the mainland during the times she attended RRB and Congress.

We demonstrate here that mitochondrial translation products synthesized by isolated yeast mitochondria are subject to rapid proteolysis. The loss of label from mitochondrial peptides synthesized in vitro comes from two distinct pools of peptides: one that is rapidly degraded (t1/2 of minutes) and one that is much more resistant to proteolysis (t1/2 of hours). As the length of the incubation period increases, the percentage of labelled peptides in the rapidly-turning-over pool decreases and cannot be detected after 60 min of incubation. This proteolysis is inhibited by chloramphenicol and is dependent on the presence of ATP. The loss of label during the chase occurs from fully completed translation products. The proteolysis observed here markedly affects measurements of rates of mitochondrial protein synthesis in isolated yeast mitochondria. In earlier work, in which proteolysis was not considered, mitochondrial translation was thought to stop after 20-30 min of incubation. In the present study, by taking proteolysis into account, we demonstrate that the rate of translation in isolated mitochondria is actually constant for nearly 60 min and then decreases to near zero by 80 min of incorporation. These findings have allowed us to devise a procedure for measuring the 'true' rate of translation in isolated mitochondria. In addition, they suggest that mitochondrial translation products which normally assemble with nuclear-encoded gene products into multimeric enzyme complexes are unstable without their nuclear-encoded counterparts.

One aim of this investigation was to determine whether the cardiac enlargement observed with glucocorticoid treatment is temporary or remains a permanent adaptation if steroid treatment is prolonged. A second aim was to study whether myosin heavy chain (MHC) synthesis rates are coordinated with the cardiac mass responses. Female rats received either a vehicle (1% aqueous carboxymethyl cellulose in saline) or hydrocortisone 21-acetate for 1, 3, 7, 11, and 15 days. Peak cardiac enlargement (10-15%) was observed after 7 days of hormone treatment in two separate series of experiments. The enlargement was maintained through 11 days of steroid injections but by 15 days had declined toward control levels. MHC synthesis measurements were performed by constant infusion of [3H]leucine. Leucine specific activities were similar among precursor pools (intracellular, extracellular, and leucyl-tRNA) and did not vary with steroid treatments. Fractional synthesis rates of ventricular MHC (%/day) did not change during the period of increase in ventricular mass but were reduced to 56-59% of controls (-11/19.5) at 7 and 11 days of treatment, when ventricular mass increases were highest. MHC breakdown (%/day) was reduced to approximately 60% (-11.5/18.7) of controls at 7 and 11 days. Changes in total protein synthesis, which was measured in isolated perfused hearts, were similar to the MHC responses and indicated that the alterations in MHC synthesis are synchronized with the hormonal effects on total protein metabolism. These results demonstrate that peak cardiac enlargement is not maintained with long-term glucocorticoid treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

The rates of synthesis of mitochondrial proteins by both the cytoplasmic and mitochondrial protein synthetic systems, as well as parameters of respiration, were measured and compared in mitochondria isolated from fresh, control perfused, and insulin-perfused rat hearts. The respiratory control ratio (RCR) in mitochondria from fresh hearts was 8.1 +/- 0.4 and decreased to 6.0 +/- 0.2 (P less than 0.001 vs. fresh) in mitochondria from control perfused hearts and to 6.7 +/- 0.2 (P less than 0.005 vs. fresh and P less than 0.02 vs. control perfused) for mitochondria from hearts perfused in the presence of insulin. A positive correlation between the RCR and the rate of mitochondrial translation was demonstrated in mitochondria from fresh hearts. In mitochondria isolated from control perfused hearts, the rate of protein synthesis decreased to 84 +/- 3% of the fresh rate after 30 min of perfusion and fell further to 64 +/- 3% after 3 h of perfusion. The inclusion of insulin in the perfusion buffer stimulated mitochondrial protein synthesis 1.2-fold by 1 h (P less than 0.005) and 1.34-fold by 3 h of perfusion (P less than 0.001). The addition of insulin to 1-h control perfused hearts shifted the rate of mitochondrial protein synthesis from the control level to the insulin-perfused level within 30 min of additional perfusion, whereas 1 h was required to shift the RCR values of these mitochondria from control levels to insulin-perfused levels. Thus, whereas RCR was a useful predictor of mitochondrial translation rates, it did not account for the effects of insulin on mitochondrial translation.(ABSTRACT TRUNCATED AT 250 WORDS)

Although much is now known with regard to the processes of mammalian mitochondrial gene expression, relatively little is known concerning the quantitative regulation of this pathway in response to hormones or other physiological stimuli. This has been caused, in large part, by the lack of adequate assay systems in which such processes can be meaningfully measured. The purpose of this and the companion paper [E. E. McKee, B. L. Grier, G. S. Thompson, A. C. F. Leung, and J. D. McCourt. Am. J. Physiol. 258 [Endocrinol. Metab. 21):E503-E510, 1990] is to describe a system in which the quantitative regulation of mitochondrial protein synthesis in rat heart can be investigated. In this report the conditions for mitochondrial isolation and labeling are described, and the importance of isolating intact, tightly coupled mitochondria in obtaining high and reliable rates of protein synthesis is demonstrated. The highest levels of protein synthesis are obtained in mitochondria isolated from hearts perfused and homogenized in the presence of subtilisin, conditions in which the fastest rates of state 3 respiration and the highest respiratory control ratios are also observed. Analysis of the free amino acid pools indicates that isolated heart mitochondria have a negligible level of endogenous methionine as well as other amino acids. As a result, the concentration and specific radioactivity of the [35S]methionine pool serving protein synthesis could be easily determined. Optimal translation occurred at 30 degrees C at a pH of 7.0-7.2 and required the addition of methionine (20 microM), the other 19 amino acids (0.1 mM each), K+ (60-90 mM), Cl- (30-90 mM), Mg2+ (0.5-5 mM), and bovine serum albumin (1 mg/ml). As shown in the companion paper, adenine nucleotide (0.5-4.0 mM) and oxidizable substrate (10-20 mM glutamate) are also required for isolated heart mitochondrial protein synthesis. Analysis of labeled mitochondrial translation products demonstrated that bona fide mitochondrial peptides were synthesized.

The goal of this paper was to determine the effects of 3,5,3'-triiodothyronine (T3)-thyroxine-induced cardiac hypertrophy on the rates of synthesis of mitochondrial proteins by both the cytoplasmic and mitochondrial protein synthesis systems and to compare the results with total protein synthesis and cardiac enlargement. Daily injections of T3-thyroxine in the rat resulted in a 25% increase in the growth of the ventricle compared with controls. The cytoplasmic synthesis of both mitochondrial and total proteins as measured in the isolated perfused heart was stimulated by T3-thyroxine injection to a peak of 155 and 146%, respectively, of vehicle-injected controls after 3 days of hormone treatment. This peak was followed by a gradual decline in stimulation in total protein synthesis to 132% of control by 9 days of injection, whereas the decline in stimulation of cytoplasmic synthesis of mitochondrial proteins was significantly steeper, falling to 119% of vehicle control. The rate of protein synthesis within the mitochondrial compartment was also measured during the time course of T3-thyroxine-induced hypertrophy. These rates were measured in an isolated intact heart mitochondrial protein synthesis system described and characterized in the companion papers [E. E. McKee, B. L. Grier, G. S. Thompson, and J. D. McCourt. Am. J. Physiol. 258 (Endocrinol. Metab. 21): E492-E502, 1990; and E. E. McKee, B. L. Grier, G. S. Thompson, A. C. F. Leung, and J. D. McCourt. Am. J. Physiol. 258 (Endocrinol. Metab. 21): E503-E510, 1990]. Rates of mitochondrial protein synthesis were dramatically stimulated by T3-thyroxine injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Although much is now known with regard to the processes of mammalian mitochondrial gene expression, relatively little is known concerning the quantitative regulation of this pathway in response to hormones or other physiological stimuli. In this paper the potential coupling of mitochondrial metabolism to mitochondrial protein synthesis was investigated and the concentration of nucleotides and substrates for optimal translation in isolated rat heart mitochondria was determined. It was demonstrated that optimal isolated heart mitochondrial protein synthesis required the presence of an oxidizable substrate. Of the substrates tested, glutamate (20 mM) supported translation best followed by malate, succinate, and alpha-ketoglutarate, whereas pyruvate supported synthesis poorly. Unlike other recent mammalian mitochondrial systems, the presence of an oxidizable substrate was required for translation even in the presence of medium ATP and an exogenous energy-generating system. Mitochondrial translation also required the presence of adenine nucleotide that could be added as ADP or ATP; however, ATP added above 0.5 mM became progressively inhibitory. As a result, synthesis was supported significantly better by ATP synthesized by the system from added ADP, than by ATP added directly to the system. However, if the phosphorylation of ADP was prevented by limiting the phosphate concentration, ADP itself strongly inhibited mitochondrial protein synthesis. This inhibition appeared to be closely related to the energy charge of the system rather than to absolute levels of ADP, indicating for the first time that mitochondrial translation, like its cytoplasmic counterpart is regulated by energy charge. Last, this system did not require the inhibition of guanine nucleotide or exogenous energy-generating systems.(ABSTRACT TRUNCATED AT 250 WORDS)

Data from one psychological and one psychiatric agency were collected to determine if psychotherapists' treatment decisions about opposite-sex persons might be influenced by sex-role prescriptions for dealing with sexual impulses. Accordingly, male therapists were hypothesized to prolong and female therapists to avoid treatment situations likely to arouse their sexual curiosities. The results at both facilities provide some support for these notions and, if generalizable, establish sex-role primed countertransference as a factor in patient selection and termination.